Neuroprotective Effect of Ceftriaxone on MPTP‐Induced Parkinson’s Disease Mouse Model by Regulating Inflammation and Intestinal Microbiota
Open accessAbstract
Parkinson’s disease (PD) is a common degenerative disease of the central nervous system. Although some drugs can alleviate the progress of PD, their long‐term use will lead to complications, so it is still necessary to find new drugs to delay or cure PD effectively. In view of the difficulty in developing new drugs, it is imperative to discover new functions of existing compounds that could be used to treat PD. In this study, 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) was used to induce PD symptoms in a mouse model. Subsequently, these mice were treated with the antibiotic ceftriaxone. Ceftriaxone alleviated the behavioural and neuropathological changes induced by MPTP, downregulated the expression of glial fibrillary acidic protein (GFAP) and ionised calcium‐binding adapter molecule 1 (Iba1) as markers of astroglia and microglia, respectively, and reduced the expression of neuroinflammation‐related Toll‐like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), and phosphorylated nuclear factor kappa‐B (p‐NF‐ κ B)/NF‐ κ B in the brain of PD mice. In addition, ceftriaxone reduced the abundance of pathogenic bacteria of the genus Proteus and increased the abundance of probiotic Akkermansia . Finally, ceftriaxone treatment increased the expression of the tight junction proteins zona occludens‐1(ZO‐1) and occludin in the colon, decreased the expression of the inflammation‐related proteins TLR4, MyD88, and NF‐ κ B in the colon, and decreased the serum concentration of the proinflammatory cytokines interleukin‐1 β (IL‐1 β ), IL‐6, and tumour necrosis factor‐ α (TNF‐ α ). These results indicate that ceftriaxone had a neuroprotective effect on MPTP‐induced PD mice, and its neuroprotective effect could be through regulating inflammation and intestinal microbiota. While we showed that ceftriaxone exerts a neuroprotective effect in an MPTP‐induced PD mouse model, our findings are limited to the short‐term effects of ceftriaxone. Additional work using transgenic mice is required to determine the long‐term effects of ceftriaxone. In addition, the dose and frequency of ceftriaxone use should be evaluated.
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Written from the paper’s full text.
TL;DR
Ceftriaxone improved motor dysfunction and neuropathology in MPTP-induced Parkinson’s disease mice while reducing glial activation, TLR4/NF-κB inflammation, and systemic cytokines. Its effects were accompanied by altered gut microbiota, including reduced *Proteus* and increased *Akkermansia*, suggesting neuroprotection via inflammation and intestinal microbiota regulation.
Key findings
- Ceftriaxone alleviated MPTP-induced motor deficits: pole test times were M vs. C = 17.72 s vs. 10.89 s (p < 0.001) and MCEF vs. M = 11.67 s vs. 17.72 s (p < 0.001); open-field total distance was M vs. C = 2169 cm vs. 3806 cm, central-area distance 510.6 cm vs. 890.7 cm, and central entries 16.5 vs. 33.75 (p < 0.001).
- In the brain, ceftriaxone increased TH, GLT-1, BDNF, and GDNF, reduced α-synuclein, downregulated GFAP and Iba1, and lowered TLR4, MyD88, and p-p65/NF-κB pathway proteins in the substantia nigra.
- Ceftriaxone reduced gut α-diversity by Chao1 and Faith_pd indices, reduced *Bifidobacterium* and *Proteus* (p < 0.01), and increased probiotic *Akkermansia* and *Prevotella*.
- Ceftriaxone increased colonic ZO-1 and occludin, decreased colonic TLR4, MyD88, and NF-κB, and reduced serum IL-6 (M vs. C = 154.7 pg/ml vs. 17.94 pg/ml), IL-1β (65.93 pg/ml vs. 12.74 pg/ml), and TNF-α (147.2 pg/ml vs. 14.47 pg/ml) (p < 0.01).
Methods
- Male C57BL/6 mice (25–30 g) were divided into six groups of 15: control, MPTP (20 mg/kg i.p. daily for 7 days), MPTP + ceftriaxone (200 mg/kg i.p. daily for 7 days), MPTP + ceftriaxone followed by PD fecal microbiota transplantation (FMT), FMT alone, and FMT followed by ceftriaxone.
- Behavioral testing used pole and open-field tests; brain and colon tissues were analyzed by immunofluorescence and Western blotting; serum cytokines were measured by ELISA; fecal microbiota was analyzed by 16S rDNA V4 sequencing on Illumina with QIIME2/dada2 (GenBank PRJNA659569).
- Data were analyzed with one-way ANOVA followed by Tukey’s test; p < 0.05 was considered significant.
Limitations
- The paper states that findings are limited to short-term effects of ceftriaxone, that additional work using transgenic mice is required to determine long-term effects, and that the dose and frequency of ceftriaxone use should be evaluated.
- Evident from the text: only male C57BL/6 mice were used, so sex-specific effects were not assessed; the model is an MPTP-induced subacute PD mouse model rather than a transgenic or long-term model.
- Evident from the text: microbiota sequencing used N = 8 per group, while behavioral and other experiments used groups of 15 mice, and ceftriaxone’s antibiotic activity is not fully separated from its proposed neuroprotective mechanism.
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0 of 51 cited sources checked · 0 supported · 0 flagged
- Findingown data
Ceftriaxone decreased serum concentration of IL-1β in PD mice.
“decreased the serum concentration of the proinflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumour necrosis factor-α (TNF-α)”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone decreased expression of TLR4 in the colon of PD mice.
“decreased the expression of the inflammation-related proteins TLR4, MyD88, and NF-κB in the colon”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone increased expression of tight junction protein ZO-1 in the colon of PD mice.
“ceftriaxone treatment increased the expression of the tight junction proteins zona occludens-1(ZO-1) and occludin in the colon”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone decreased expression of MyD88 in the colon of PD mice.
“decreased the expression of the inflammation-related proteins TLR4, MyD88, and NF-κB in the colon”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone increased expression of tight junction protein occludin in the colon of PD mice.
“ceftriaxone treatment increased the expression of the tight junction proteins zona occludens-1(ZO-1) and occludin in the colon”
Quote in the paperSubstantial claim
- Findingown data
Ceftriaxone decreased serum concentration of IL-6 in PD mice.
“decreased the serum concentration of the proinflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumour necrosis factor-α (TNF-α)”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone decreased expression of NF-κB in the colon of PD mice.
“decreased the expression of the inflammation-related proteins TLR4, MyD88, and NF-κB in the colon”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone decreased serum concentration of TNF-α in PD mice.
“decreased the serum concentration of the proinflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumour necrosis factor-α (TNF-α)”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone downregulated GFAP expression in the brain of MPTP-induced PD mice.
“downregulated the expression of glial fibrillary acidic protein (GFAP) and ionised calcium-binding adapter molecule 1 (Iba1) as markers of astroglia and microglia, respectively”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone reduced the abundance of pathogenic bacteria of the genus Proteus in PD mice.
“ceftriaxone reduced the abundance of pathogenic bacteria of the genus Proteus”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone increased the abundance of probiotic Akkermansia in PD mice.
“increased the abundance of probiotic Akkermansia”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone reduced expression of MyD88 in the brain of MPTP-induced PD mice.
“reduced the expression of neuroinflammation-related Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), and phosphorylated nuclear factor kappa-B (p-NF-κB)/NF-κB in the brain of PD mice”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone downregulated Iba1 expression in the brain of MPTP-induced PD mice.
“downregulated the expression of glial fibrillary acidic protein (GFAP) and ionised calcium-binding adapter molecule 1 (Iba1) as markers of astroglia and microglia, respectively”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone reduced expression of p-NF-κB/NF-κB in the brain of MPTP-induced PD mice.
“reduced the expression of neuroinflammation-related Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), and phosphorylated nuclear factor kappa-B (p-NF-κB)/NF-κB in the brain of PD mice”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone reduced expression of TLR4 in the brain of MPTP-induced PD mice.
“reduced the expression of neuroinflammation-related Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), and phosphorylated nuclear factor kappa-B (p-NF-κB)/NF-κB in the brain of PD mice”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone reduced inflammation by lowering expression of TLR4 in the TLR4/NF-κB inflammatory pathway in the substantia nigra of mice.
“this drug reduced inflammation by lowering the expression of TLR4, MyD88, and p-p65 in the TLR4/NF-κB inflammatory pathway in the substantia nigra of mice”
Quote in the paperSubstantial claim - Findingown data
MPTP treatment decreased expression of neurotrophic factors compared with control.
“MPTP treatment significantly decreased the expression of TH, GLT-1, and neurotrophic factors”
Quote in the paperSubstantial claim - Findingown data
Transplantation of microbiota from PD mice worsened neuropathological characteristics in the MCEFF and FMT groups.
“The transplantation of microbiota from PD mice worsened the neuropathological characteristics in the MCEFF and FMT groups”
Quote in the paperSubstantial claim - Findingown data
There was no obvious difference in Chao1 and Faith_pd indices between the C and M groups.
“The Chao1 index and Faith_pd index showed that there was no obvious difference between the C and M groups”
Quote in the paperNot a substantial claim - Findingown data
Ceftriaxone significantly reduced the colonic inflammatory proteins and systemic inflammatory cytokines caused by MPTP and faecal microbiota transplantation from PD mice.
“The use of ceftriaxone significantly reduced the colonic inflammatory proteins and systemic inflammatory cytokines caused by MPTP and faecal microbiota transplantation from PD mice”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone significantly reduced α-diversity in the MCEF, MCEFF, and FCEF groups.
“while the use of ceftriaxone significantly reduced the α-diversity in the MCEF, MCEFF, and FCEF groups”
Quote in the paperNot a substantial claim - Findingown data
MPTP-treated mice showed significant motor dysfunction compared with control in the pole test (M vs C = 17.72 s vs 10.89 s; p < 0.001).
“MPTP-treated mice showed significant motor dysfunction compared with the control group (M vs.C = 17.72 s vs.10.89 s; p < 0.001)”
Quote in the paperSubstantial claim - Findingown data
MPTP promoted serum IL-6 expression (M vs. C = 154.7 pg/ml vs. 17.94 pg/ml; p < 0.01).
“promoted the expression of inflammatory cytokines IL-6 (M vs.C = 154.7 pg/ml vs.17.94 pg/ml; p < 0.01)”
Quote in the paperSubstantial claim - Findingown data
MPTP promoted serum TNF-α expression (M vs. C = 147.2 pg/ml vs. 14.47 pg/ml; p < 0.01).
“TNF-α (M vs.C = 147.2 pg/ml vs.14.47 pg/ml; p < 0.01)”
Quote in the paperSubstantial claim - Findingown data
MPTP-treated mice showed decreased distance moved in the central area in the open field test compared with control (M vs C = 510.6 cm vs 890.7 cm; p < 0.001).
“distance moved in the central area (M vs.C = 510.6 cm vs. 890.7 cm; Figure 1(d))”
Quote in the paperSubstantial claim - Findingown data
Use of ceftriaxone (MCEF, MCEFF, and FCEF groups) greatly changed microbial diversity compared with the C group.
“the use of ceftriaxone (MCEF, MCEFF, and FCEF groups) greatly changed the microbial diversity compared with the C group”
Quote in the paperSubstantial claim - Findingown data
MPTP treatment increased expression of α-syn compared with control.
“significantly increased the expression of α-syn compared with the C group”
Quote in the paperSubstantial claim - Findingown data
MPTP markedly enhanced the abundance of the genera Proteus, Adlercreutzia, Bifidobacterium, Clostridium, and Dorea in the M group compared with the C group.
“markedly enhanced the abundance of the genera Proteus, Adlercreutzia, Bifidobacterium, Clostridium, and Dorea in the M group compared with the C group”
Quote in the paperSubstantial claim - Findingown data
Intraperitoneal injection of ceftriaxone reversed the behavioural changes caused by MPTP and PD faecal microbiota.
“Intraperitoneal injection of ceftriaxone reversed the behavioural changes caused by MPTP and PD faecal microbiota.”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone reversed the enhanced glial activation and increased TLR4/NF-κB inflammatory proteins caused by transplantation of microbiota from PD mice.
“the use of ceftriaxone reversed these changes”
Quote in the paperSubstantial claim - Findingown data
MPTP increased the expression of TLR4, MyD88, and p-p65 in the M group compared with the C group.
“increased the expression of TLR4, MyD88, and p-p65 in the M group compared with the C group (Figure 6(b))”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone enhanced expression of neurotrophic factors in MPTP-induced PD mice.
“the use of ceftriaxone greatly enhanced the expression of TH, GLT-1, and neurotrophic factors”
Quote in the paperSubstantial claim - Findingown data
PCoA analysis indicated that samples in the M group were far from samples in the C group.
“PCoA analysis indicated that the samples in the M group were far from samples in the C group”
Quote in the paperNot a substantial claim - Findingown data
MPTP treatment decreased expression of GLT-1 compared with control.
“MPTP treatment significantly decreased the expression of TH, GLT-1, and neurotrophic factors”
Quote in the paperSubstantial claim - Findingown data
MPTP reduced TH expression in the substantia nigra of mice.
“MPTP significantly reduced the TH expression in the substantia nigra of mice in the M group (Figure 2(a))”
Quote in the paperSubstantial claim - Findingown data
Motor dysfunction recurred in the MCEFF group after transplantation of fecal microbiota from PD mice (MCEFF vs MCEF = 13.83 s vs 11.67 s).
“motor dysfunction recurred in the MCEFF group, which underwent transplantation of faecal microbiota from PD mice (MCEFF vs.MCEF = 13.83 s vs.11.67 s)”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone treatment reduced the abundance of the genera Bifidobacterium and Proteus (p < 0.01).
“Ceftriaxone treatment reduced the abundance of the genera Bifidobacterium and Proteus (p < 0.01)”
Quote in the paperSubstantial claim - Findingown data
Transplantation of microbiota from PD mice enhanced activation of glia in mice.
“Transplantation of microbiota from PD mice enhanced the activation of glia”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone reversed movement impairment caused by fecal microbiota transplantation from PD mice in the pole test (FCEF vs FMT = 12.16 s vs 15.74 s).
“the use of ceftriaxone could reverse the movement impairment caused by faecal microbiota transplantation from PD mice (FCEF vs.FMT = 12.16 s vs.15.74 s; Figure 1(b))”
Quote in the paperSubstantial claim - Findingown data
MPTP significantly reduced the expression of ZO-1 and occludin.
“MPTP significantly reduced the expression of ZO-1 and occludin (Figure 6(a))”
Quote in the paperSubstantial claim - Findingown data
MPTP promoted serum IL-1β expression (M vs. C = 65.93 pg/ml vs. 12.74 pg/ml; p < 0.01).
“IL-1β (M vs.C = 65.93 pg/ml vs.12.74 pg/ml; p < 0.01)”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone reversed behavioural and mental changes caused by PD microbiota in the FCEF group.
“the use of ceftriaxone reversed the behavioural and mental changes of the mice caused by PD microbiota in the FCEF group”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone reduced inflammation by lowering expression of MyD88 in the TLR4/NF-κB inflammatory pathway in the substantia nigra of mice.
“this drug reduced inflammation by lowering the expression of TLR4, MyD88, and p-p65 in the TLR4/NF-κB inflammatory pathway in the substantia nigra of mice”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone significantly alleviated MPTP-induced motor dysfunction in the pole test (MCEF vs M = 11.67 s vs 17.72 s; p < 0.001).
“ceftriaxone significantly alleviated MPTP-induced motor dysfunction (MCEF vs.M = 11.67 s vs.17.72 s; p < 0.001)”
Quote in the paperSubstantial claim - Findingown data
Transplantation of faecal microbiota from PD mice (MCEFF and FMT groups) significantly changed microbial diversity compared with the C group.
“the transplantation of faecal microbiota from PD mice (MCEFF and FMT groups) significantly changed the microbial diversity compared with the C group”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone treatment increased the abundance of the probiotic genera Akkermansia and Prevotella.
“increased the abundance of the probiotic genera Akkermansia and Prevotella”
Quote in the paperSubstantial claim - Findingown data
MPTP reduced the abundance of the phylum Firmicutes and the genera Akkermansia, Prevotella, and Ruminococcus in the M group compared with the C group.
“MPTP reduced the abundance of the phylum Firmicutes and the genera Akkermansia, Prevotella, and Ruminococcus”
Quote in the paperSubstantial claim - Findingown data
Transplantation of PD microbiota decreased exploratory ability of mice in the MCEFF and FMT groups.
“In the MCEFF and FMT groups, the transplantation of PD microbiota decreased the exploratory ability of mice”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone reduced activation of glia via downregulating GFAP expression in the substantia nigra of mice.
“ceftriaxone significantly reduced the activation of glia via downregulating the expression of GFAP (a marker of astrocytes) and Iba1 (a marker of microglia) in the substantia nigra of mice”
Quote in the paperSubstantial claim - Findingown data
Transplantation of fecal microbiota from PD mice to normal mice caused motor impairment compared with control in the pole test (FMT vs C = 15.74 s vs 10.89 s; p < 0.01).
“when we transplanted the faecal microbiota of PD mice to normal mice, the mice in the FMT group showed motor impairment compared with the control group (FMT vs.C = 15.74 s vs 10.89 s; p < 0.01)”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone enhanced expression of TH in MPTP-induced PD mice.
“the use of ceftriaxone greatly enhanced the expression of TH, GLT-1, and neurotrophic factors”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone enhanced expression of GLT-1 in MPTP-induced PD mice.
“the use of ceftriaxone greatly enhanced the expression of TH, GLT-1, and neurotrophic factors”
Quote in the paperSubstantial claim - Findingown data
Transplantation of microbiota from PD mice increased levels of TLR4/NF-κB inflammatory proteins in mice.
“increased the levels of TLR4/NF-κB inflammatory proteins”
Quote in the paperSubstantial claim - Findingown data
MPTP-treated mice showed decreased number of entries in the central area in the open field test compared with control (M vs C = 16.5 vs 33.75; p < 0.001).
“the number of entries in the central area (M vs.C = 16.5 vs.33.75; Figure 1(e)) (p < 0.001)”
Quote in the paperSubstantial claim - Findingown data
Mice receiving faecal microbiota from PD mice also showed similar behaviours to MPTP-treated mice.
“the mice receiving faecal microbiota from PD mice also showed similar behaviours”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone reduced expression of α-syn in MPTP-induced PD mice.
“reduced the expression of α-syn”
Quote in the paperSubstantial claim - Findingown data
The number of unique OTUs in the C, M, MCEF, MCEFF, FMT, and FCEF groups is 510, 302, 214, 240, 521, and 104, respectively.
“the number of unique OTUs in the C, M, MCEF, MCEFF, FMT, and FCEF groups is 510, 302, 214, 240, 521, and 104, respectively”
Quote in the paperNot a substantial claim - Findingown data
Ceftriaxone reduced inflammation by lowering expression of p-p65 in the TLR4/NF-κB inflammatory pathway in the substantia nigra of mice.
“this drug reduced inflammation by lowering the expression of TLR4, MyD88, and p-p65 in the TLR4/NF-κB inflammatory pathway in the substantia nigra of mice”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone reduced activation of glia via downregulating Iba1 expression in the substantia nigra of mice.
“ceftriaxone significantly reduced the activation of glia via downregulating the expression of GFAP (a marker of astrocytes) and Iba1 (a marker of microglia) in the substantia nigra of mice”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone increased exploratory ability of MPTP-induced PD mice in the open field test.
“the use of ceftriaxone increased the exploratory ability of MPTP-induced PD mice”
Quote in the paperSubstantial claim - Findingown data
MPTP treatment reduced the α-diversity of the intestinal microbiota.
“we found that MPTP treatment reduced the α-diversity of the intestinal microbiota”
Quote in the paperSubstantial claim - Findingown data
Ceftriaxone restored the expression of BDNF and GDNF in MPTP-induced PD mice.
“Our results showed that ceftriaxone restored the expression of BDNF and GDNF in MPTP-induced PD mice”
Quote in the paperSubstantial claim - Findingown data
The abundance of the genera Akkermansia and Prevotella was increased in the ceftriaxone-treated groups.
“we found that the abundance of the genera Akkermansia and Prevotella was increased in the ceftriaxone-treated groups”
Quote in the paperSubstantial claim - Findingown data
The results reported by Petrov et al. and our research consistently showed that the abundance of Bifidobacterium in PD is increased.
“the results reported by Petrov et al. [37] and our research consistently showed that the abundance of Bifidobacterium in PD is increased.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [37] Petrov V. A. Saltykova I. V. Zhukova I. A. Analysis of gut microbiota in patients with Parkinson’s disease Bulletin of Experimental Biology and Medicine 2017 162 6 734 737 10.1007/s10517-017-3700-7 2-s2.0-85018483587 28429209 source
Not checked in the free run.
- Findingown data
Ceftriaxone treatment also significantly reduced the α-diversity of the intestinal microbiota.
“Although ceftriaxone treatment also significantly reduced the α-diversity of the intestinal microbiota”
Quote in the paperNot a substantial claim - Findingown data
Our results confirmed that ceftriaxone could increase TH and GLT-1 expression in mouse substantia nigra.
“our results also confirmed that ceftriaxone could increase TH and GLT-1 expression in mouse substantia nigra”
Quote in the paperSubstantial claim - Interpretationown data
Ceftriaxone had a neuroprotective effect on MPTP-induced PD mice.
“These results indicate that ceftriaxone had a neuroprotective effect on MPTP-induced PD mice”
Quote in the paperSubstantial claim - Interpretationnone given
The findings are limited to the short-term effects of ceftriaxone.
“our findings are limited to the short-term effects of ceftriaxone”
Quote in the paperNot a substantial claim - Interpretationown data
Ceftriaxone alleviated the behavioural and neuropathological changes induced by MPTP in mice.
“Ceftriaxone alleviated the behavioural and neuropathological changes induced by MPTP”
Quote in the paperSubstantial claim - Interpretationown data
Ceftriaxone's neuroprotective effect could be through regulating inflammation and intestinal microbiota.
“its neuroprotective effect could be through regulating inflammation and intestinal microbiota”
Quote in the paperSubstantial claim - Premisecitation
When TH is reduced to a certain threshold, it causes the motor symptoms of PD.
“when it is reduced to a certain threshold, it will cause the motor symptoms of PD [24]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [24] Daubner S. C. Le T. Wang S. Tyrosine hydroxylase and regulation of dopamine synthesis Archives of Biochemistry and Biophysics 2011 508 1 1 12 10.1016/j.abb.2010.12.017 2-s2.0-79952449396 21176768 PMC3065393 source
Not checked in the free run.
- Premisecitation
The excitotoxicity of glutamate plays an important role in the pathogenesis of PD.
“the excitotoxicity of glutamate plays an important role in the pathogenesis of PD [25]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [25] Ambrosi G. Cerri S. Blandini F. A further update on the role of excitotoxicity in the pathogenesis of Parkinson's disease Journal of Neural Transmission 2014 2014 121 849 859 10.1007/s00702-013-1149-z 2-s2.0-84906868160 24380931 source
Not checked in the free run.
- Premisecitation
Ceftriaxone exhibits a neuroprotective effect in addition to its antibacterial effect in PD.
“it exhibits a neuroprotective effect in addition to its antibacterial effect in PD [15, 20]”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [15] Kaur B. Prakash A. Ceftriaxone attenuates glutamate-mediated neuro-inflammation and restores BDNF in MPTP model of Parkinson's disease in rats Pathophysiology 2017 24 2 71 79 10.1016/j.pathophys.2017.02.001 2-s2.0-85013825573 28245954 source
Not checked in the free run.
- cites [20] Bisht R. Kaur B. Gupta H. Prakash A. Ceftriaxone mediated rescue of nigral oxidative damage and motor deficits in MPTP model of Parkinson's disease in rats Neurotoxicology 2014 44 71 79 10.1016/j.neuro.2014.05.009 2-s2.0-84904261643 25053526 source
Not checked in the free run.
- Premisecitation
Some antibiotics, such as ceftriaxone, have neuroprotective properties unrelated to their antibacterial activity.
“some antibiotics, such as ceftriaxone, have been reported to have neuroprotective properties that are unrelated to their antibacterial activity [13].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [13] Rothstein J. D. Patel S. Regan M. R. β-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression Nature 2005 433 7021 73 77 10.1038/nature03180 2-s2.0-19944428649 15635412 source
Not checked in the free run.
- Premisecitation
Ceftriaxone exerts a neuroprotective effect in various neurodegenerative diseases, such as AD, PD, ALS, and HD.
“Subsequent studies have proved that ceftriaxone exerts a neuroprotective effect in various neurodegenerative diseases, such as AD [14], PD [15], amyotrophic lateral sclerosis (ALS) [16], and Huntington's disease (HD) [17].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [14] Tikhonova M. A. Amstislavskaya T. G. Belichenko V. M. Modulation of the expression of genes related to the system of amyloid-beta metabolism in the brain as a novel mechanism of ceftriaxone neuroprotective properties BMC Neuroscience 2018 19 S1 p. 13 10.1186/s12868-018-0412-5 2-s2.0-85045537930 29745864 PMC5998892 source
Not checked in the free run.
- cites [15] Kaur B. Prakash A. Ceftriaxone attenuates glutamate-mediated neuro-inflammation and restores BDNF in MPTP model of Parkinson's disease in rats Pathophysiology 2017 24 2 71 79 10.1016/j.pathophys.2017.02.001 2-s2.0-85013825573 28245954 source
Not checked in the free run.
- cites [16] Nizzardo M. Nardini M. Ronchi D. Beta-lactam antibiotic offers neuroprotection in a spinal muscular atrophy model by multiple mechanisms Experimental Neurology 2011 229 2 214 225 10.1016/j.expneurol.2011.01.017 2-s2.0-79956158030 21295027 source
Not checked in the free run.
- Premisecitation
The intestinal microbiota plays a key role in the development and treatment of PD through the brain-gut axis.
“The intestinal microbiota plays a key role in the development and treatment of PD through the brain-gut axis [9].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [9] Sun M. F. Shen Y. Q. Dysbiosis of gut microbiota and microbial metabolites in Parkinson's disease Ageing Research Reviews 2018 45 53 61 10.1016/j.arr.2018.04.004 2-s2.0-85046665507 29705121 source
Not checked in the free run.
- Premisecitation
Patients with PD have an intestinal microbiota disorder, specifically increased abundance of Lactobacillus and Enterobacteriaceae and decreased abundance of Prevotella, Clostridium coccoides, and Bacteroides fragilis.
“Patients with PD have an intestinal microbiota disorder, which is specifically manifested in the increased abundance of Lactobacillus and Enterobacteriaceae and the decreased abundance of Prevotella, Clostridium coccoides, and Bacteroides fragilis [9, 10].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [9] Sun M. F. Shen Y. Q. Dysbiosis of gut microbiota and microbial metabolites in Parkinson's disease Ageing Research Reviews 2018 45 53 61 10.1016/j.arr.2018.04.004 2-s2.0-85046665507 29705121 source
Not checked in the free run.
- cites [10] Yang D. Zhao D. Ali Shah S. Z. The role of the gut microbiota in the pathogenesis of Parkinson's disease Frontiers in Neurology 2019 10 p. 1155 10.3389/fneur.2019.01155 PMC6851172 31781020 source
Not checked in the free run.
- Premisecitation
Glutamate in the brain is mainly cleared by GLT-1.
“Glutamate in the brain is mainly cleared by GLT-1”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [26] Ferrarese C. Tremolizzo L. Rigoldi M. Decreased platelet glutamate uptake and genetic risk factors in patients with Parkinson's disease Neurological Sciences 2001 22 1 65 66 10.1007/s100720170049 2-s2.0-18044399452 11487204 source
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- Premisecitation
There is an increase in proinflammatory microorganisms in the intestinal microbiota of PD patients.
“There is an increase in proinflammatory microorganisms in the intestinal microbiota of PD patients [41]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [41] Sampson T. R. Debelius J. W. Thron T. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease Cell 2016 167 6 1469 80.e12 10.1016/j.cell.2016.11.018 2-s2.0-85001930733 27912057 PMC5718049 source
Not checked in the free run.
- Premisecitation
The signalling pathway mediated by TLR4 plays an important role in PD.
“The signalling pathway mediated by TLR4 plays an important role in PD [33]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [33] Perez-Pardo P. Dodiya H. B. Engen P. A. Role of TLR4 in the gut-brain axis in Parkinson's disease: a translational study from men to mice Gut 2019 68 5 829 843 10.1136/gutjnl-2018-316844 2-s2.0-85058680684 30554160 source
Not checked in the free run.
- Premisecitation
Ceftriaxone reportedly reduced the loss of dopaminergic neurons in PD patients by increasing GLT-1 expression.
“Ceftriaxone reportedly reduced the loss of dopaminergic neurons in PD patients by increasing GLT-1 expression [23]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [23] Chotibut T. Davis R. W. Arnold J. C. Ceftriaxone increases glutamate uptake and reduces striatal tyrosine hydroxylase loss in 6-OHDA Parkinson's model Molecular Neurobiology 2014 49 3 1282 1292 10.1007/s12035-013-8598-0 2-s2.0-84902546439 24297323 PMC4618839 source
Not checked in the free run.
- Interpretationreasoning
Ceftriaxone could be a potential treatment for PD.
“Ceftriaxone could be a potential treatment for PD”
Quote in the paperSubstantial claim - Premisecitation
Dysbiosis of the intestinal microbiota can lead to decreased expression of intestinal tight-junction-associated proteins.
“whose dysbiosis can lead to decreased expression of intestinal tight-junction-associated proteins”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [36] Collado M. C. Derrien M. Isolauri E. de Vos W. M. Salminen S. Intestinal integrity and Akkermansia muciniphila, a mucin-degrading member of the intestinal microbiota present in infants, adults, and the elderly Applied and Environmental Microbiology 2007 73 23 7767 7770 10.1128/aem.01477-07 2-s2.0-38449104720 17933936 PMC2168041 source
Not checked in the free run.
- Premisecitation
GLT-1 shows dysfunction or decreased expression in patients with neurodegenerative diseases such as PD, AD, or ALS.
“GLT-1 shows dysfunction or decreased expression in patients with neurodegenerative diseases such as PD [26], AD [27], or ALS [17]”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [26] Ferrarese C. Tremolizzo L. Rigoldi M. Decreased platelet glutamate uptake and genetic risk factors in patients with Parkinson's disease Neurological Sciences 2001 22 1 65 66 10.1007/s100720170049 2-s2.0-18044399452 11487204 source
Not checked in the free run.
- cites [27] Li S. Mallory M. Alford M. Tanaka S. Masliah E. Glutamate transporter alterations in Alzheimer disease are possibly associated with abnormal APP expression Journal of Neuropathology and Experimental Neurology 1997 56 8 901 911 10.1097/00005072-199708000-00008 2-s2.0-0030872412 9258260 source
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- cites [17] Miller B. R. Dorner J. L. Shou M. Up-regulation of GLT1 expression increases glutamate uptake and attenuates the Huntington's disease phenotype in the R6/2 mouse Neuroscience 2008 153 1 329 337 10.1016/j.neuroscience.2008.02.004 2-s2.0-41949104569 18353560 PMC2424273 source
Not checked in the free run.
- May combine two claims. 12
- The quote only partly states this claim. 2
- Classified as probably not a substantial claim. 23
May combine two claims.
Findingown dataMPTP caused significant motor dysfunction and decreased exploratory ability of mice.
“MPTP caused significant motor dysfunction and decreased the exploratory ability of mice”
Quote in the paperSubstantial claimThe quote only partly states this claim.
Findingown dataMPTP-treated mice showed decreased total movement distance in the open field test compared with control (M vs C = 2169 cm vs 3806 cm; p < 0.001).
“mice in the M group showed decreased exploratory ability after injection of MPTP compared with the C group, as indicated by the total movement distance (M vs.C = 2169 cm vs.3806 cm; Figure 1(c))”
Quote in the paperSubstantial claimThe quote only partly states this claim.
Findingown dataCeftriaxone greatly enhanced the expression of intestinal tight-junction-associated proteins.
“greatly enhanced the expression of intestinal tight-junction-associated proteins”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataThere were 27 common OTUs in all groups.
“The Venn results revealed 27 common OTUs in all groups”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn our study, ceftriaxone therapy restored the MPTP-induced decrease in intestinal tight-junction-associated proteins, reducing TLR4-mediated intestinal inflammation as well as serum IL-6, IL-1β, and TNF-α expression.
“In our study, ceftriaxone therapy restored the MPTP-induced decrease in intestinal tight-junction-associated proteins, reducing TLR4-mediated intestinal inflammation as well as serum IL-6, IL-1β, and TNF-α expression.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn this study, ceftriaxone reduced the expression of GFAP and Iba1 and downregulated the expression levels of TLR4, MyD88, and p-p65, all part of the inflammatory pathway.
“In this study, we found that ceftriaxone reduced the expression of GFAP and Iba1 and downregulated the expression levels of TLR4, MyD88, and p-p65, all part of the inflammatory pathway.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataMPTP administration increased the abundance of the genera Proteus, Adlercreutzia, Bifidobacterium, and Clostridium, as well as the bacterium Proteus mirabilis.
“MPTP administration increased the abundance of the genera Proteus, Adlercreutzia, Bifidobacterium, and Clostridium, as well as the bacterium Proteus mirabilis”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
PremisecitationThere is bidirectional communication between the gut and the brain.
“Increasing evidence suggests there is bidirectional communication between the gut and the brain [6–8].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [6] Sun M. F. Zhu Y. L. Zhou Z. L. Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson's disease mice: gut microbiota, glial reaction and TLR4/TNF-α signaling pathway Brain, Behavior, and Immunity 2018 70 48 60 10.1016/j.bbi.2018.02.005 2-s2.0-85042363965 29471030 source
Not checked in the free run.
- cites [7] Quigley E. M. M. Microbiota-brain-gut axis and neurodegenerative diseases Current Neurology and Neuroscience Reports 2017 17 12 p. 94 10.1007/s11910-017-0802-6 2-s2.0-85032031823 29039142 source
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- cites [8] Obrenovich M. Jaworski H. Tadimalla T. The role of the microbiota-gut-brain axis and antibiotics in ALS and neurodegenerative diseases Microorganisms 2020 8 5 p. 784 10.3390/microorganisms8050784 32456229 PMC7285349 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationGV-971 was approved for treatment of Alzheimer's disease by the National Medical Products Administration for its ability to remodel intestinal microbiota.
“Recently, GV-971 was approved for the treatment of Alzheimer's disease (AD) by the National Medical Products Administration for its ability to remodel the intestinal microbiota.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [11] Wang X. Sun G. Feng T. Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression Cell Research 2019 29 10 787 803 10.1038/s41422-019-0216-x 2-s2.0-85072904923 31488882 PMC6796854 source
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Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationCeftriaxone exhibits a neuroprotective effect in AD.
“it exhibits a neuroprotective effect in addition to its antibacterial effect in PD [15, 20] and AD [21].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [21] Yimer E. M. Hishe H. Z. Tuem K. B. Repurposing of the β-lactam antibiotic, ceftriaxone for neurological disorders: a review Frontiers in Neuroscience 2019 13 p. 236 10.3389/fnins.2019.00236 PMC6444273 30971875 source
Not checked in the free run.
Classified as probably not a substantial claim.
Premisecitationβ-lactam antibiotics (such as ceftriaxone) have a neuroprotective effect on ischaemic brain injury.
“Rothstein et al. [13] first reported that the β-lactam antibiotics (such as ceftriaxone) have a neuroprotective effect on ischaemic brain injury.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [13] Rothstein J. D. Patel S. Regan M. R. β-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression Nature 2005 433 7021 73 77 10.1038/nature03180 2-s2.0-19944428649 15635412 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationTargeting intestinal microbiota for treatment of AD opens a new way to treat other neurological diseases.
“Targeting the intestinal microbiota for the treatment of AD opens up a new way to treat other neurological diseases [11].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [11] Wang X. Sun G. Feng T. Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression Cell Research 2019 29 10 787 803 10.1038/s41422-019-0216-x 2-s2.0-85072904923 31488882 PMC6796854 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAll experiments were conducted according to established guidelines.
“all experiments were conducted according to the established guidelines”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationCeftriaxone is a broad-spectrum antibiotic used commonly in the clinic to treat infections of the respiratory tract and urinary system.
“Ceftriaxone is a broad-spectrum antibiotic that is used commonly in the clinic to treat infections of the respiratory tract and urinary system [16]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [16] Nizzardo M. Nardini M. Ronchi D. Beta-lactam antibiotic offers neuroprotection in a spinal muscular atrophy model by multiple mechanisms Experimental Neurology 2011 229 2 214 225 10.1016/j.expneurol.2011.01.017 2-s2.0-79956158030 21295027 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationUse of antibiotics-especially macrolides and lincosamides-is related to increased risk of PD.
“it has been reported that the use of antibiotics—especially macrolides and lincosamides—is related to the increased risk of PD [12].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [12] Mertsalmi T. H. Pekkonen E. Scheperjans F. Antibiotic exposure and risk of Parkinson's disease in Finland: a nationwide case-control study Movement Disorders 2020 35 3 431 442 10.1002/mds.27924 31737957 source
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Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe study was approved by the Laboratory Animal Ethics Committee of Nanchang Royo Biotech Co., Ltd. (license No. RYE2019041502) on 15 April 2019.
“The study had been approved by the Laboratory Animal Ethics Committee of Nanchang Royo Biotech Co., Ltd. (license No. RYE2019041502) on 15 April 2019”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe dopaminergic and glutamatergic systems in the brain work together to regulate motor and cognitive functions.
“The dopaminergic and glutamatergic systems in the brain work together to regulate motor and cognitive functions [23].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [23] Chotibut T. Davis R. W. Arnold J. C. Ceftriaxone increases glutamate uptake and reduces striatal tyrosine hydroxylase loss in 6-OHDA Parkinson's model Molecular Neurobiology 2014 49 3 1282 1292 10.1007/s12035-013-8598-0 2-s2.0-84902546439 24297323 PMC4618839 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
InterpretationcitationThese results are consistent with previous reports that ceftriaxone could improve the motor dysfunction of PD.
“These results are consistent with previous reports that ceftriaxone could improve the motor dysfunction of PD [20, 22].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [20] Bisht R. Kaur B. Gupta H. Prakash A. Ceftriaxone mediated rescue of nigral oxidative damage and motor deficits in MPTP model of Parkinson's disease in rats Neurotoxicology 2014 44 71 79 10.1016/j.neuro.2014.05.009 2-s2.0-84904261643 25053526 source
Not checked in the free run.
- cites [22] Collyer R. Clancy A. Borody T. Faecal microbiota transplantation alleviates symptoms of depression in individuals with irritable bowel syndrome: a case series Medicine in Microecology 2020 6, article 100029 10.1016/j.medmic.2020.100029 source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationAt present, there is no specific medicine to cure PD.
“At present, there is no specific medicine to cure PD [19].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [19] de Bie R. M. A. Clarke C. E. Espay A. J. Fox S. H. Lang A. E. Initiation of pharmacological therapy in Parkinson's disease: when, why, and how The Lancet Neurology 2020 19 5 452 461 10.1016/S1474-4422(20)30036-3 32171387 source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationTH is the rate-limiting enzyme that participates in dopamine synthesis.
“TH is the rate-limiting enzyme that participates in dopamine synthesis”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [24] Daubner S. C. Le T. Wang S. Tyrosine hydroxylase and regulation of dopamine synthesis Archives of Biochemistry and Biophysics 2011 508 1 1 12 10.1016/j.abb.2010.12.017 2-s2.0-79952449396 21176768 PMC3065393 source
Not checked in the free run.
May combine two claims.
PremisecitationPrevotella has been reported to be correlated negatively with PD and autism spectrum disorder (ASD).
“Prevotella has been reported to be correlated negatively with PD [37] and autism spectrum disorder (ASD) [38].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [37] Petrov V. A. Saltykova I. V. Zhukova I. A. Analysis of gut microbiota in patients with Parkinson’s disease Bulletin of Experimental Biology and Medicine 2017 162 6 734 737 10.1007/s10517-017-3700-7 2-s2.0-85018483587 28429209 source
Not checked in the free run.
- cites [38] Dan Z. Mao X. Liu Q. Altered gut microbial profile is associated with abnormal metabolism activity of autism SPECTRUM disorder Gut Microbes 2020 11 5 1246 1267 10.1080/19490976.2020.1747329 32312186 PMC7524265 source
Not checked in the free run.
May combine two claims.
PremisecitationThis reduction allows the entry of pathogenic bacteria and their metabolites into the blood and increases inflammatory factors such as IL-6, IL-1β, and TNF-α.
“This reduction allows the entry of pathogenic bacteria and their metabolites into the blood and increases inflammatory factors such as IL-6, IL-1β, and TNF-α [36].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [36] Collado M. C. Derrien M. Isolauri E. de Vos W. M. Salminen S. Intestinal integrity and Akkermansia muciniphila, a mucin-degrading member of the intestinal microbiota present in infants, adults, and the elderly Applied and Environmental Microbiology 2007 73 23 7767 7770 10.1128/aem.01477-07 2-s2.0-38449104720 17933936 PMC2168041 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
InterpretationcitationThe finding that ceftriaxone restored BDNF and GDNF is consistent with the results of Kaur and Prakash.
“a finding that is consistent with the results of Kaur and Prakash [15]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [15] Kaur B. Prakash A. Ceftriaxone attenuates glutamate-mediated neuro-inflammation and restores BDNF in MPTP model of Parkinson's disease in rats Pathophysiology 2017 24 2 71 79 10.1016/j.pathophys.2017.02.001 2-s2.0-85013825573 28245954 source
Not checked in the free run.
May combine two claims.
Interpretationown dataThese results indicate that ceftriaxone could increase the expression of TH, GLT-1, and neurotrophic factors, thereby improving the motor symptoms of PD mice.
“In summary, these results indicate that ceftriaxone could increase the expression of TH, GLT-1, and neurotrophic factors, thereby improving the motor symptoms of PD mice.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationProteus mirabilis may trigger neuroinflammation and lead to pathological changes related to PD by its metabolites (such as lipopolysaccharide).
“that may trigger neuroinflammation and lead to pathological changes related to PD by its metabolites (such as lipopolysaccharide) [39]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [39] Choi J. G. Kim N. Ju I. G. Oral administration of _Proteus mirabilis_ damages dopaminergic neurons and motor functions in mice Scientific Reports 2018 8 1 p. 1275 10.1038/s41598-018-19646-x 2-s2.0-85040839877 29352191 PMC5775305 source
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May combine two claims.
Interpretationown dataCeftriaxone plays an important role in increasing the integrity of the intestinal barrier, reducing the inflammation of the colon and the brain, and has a neuroprotective effect.
“It also plays an important role in increasing the integrity of the intestinal barrier, reducing the inflammation of the colon and the brain, and has a neuroprotective effect (Supplemental Figure 1).”
Quote in the paperSubstantial claim- Rests on an assumption: The neuroinflammatory response is involved in the pathogenesis of PD.
Classified as probably not a substantial claim. May combine two claims.
PremisecitationBDNF and GDNF are dopamine-active neurotrophic proteins that can promote the survival of dopaminergic neurons and play an important role in neurite growth.
“BDNF and GDNF are dopamine-active neurotrophic proteins that can promote the survival of dopaminergic neurons and play an important role in neurite growth [28].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [28] Murer M. G. Yan Q. Raisman-Vozari R. Brain-derived neurotrophic factor in the control human brain, and in Alzheimer's disease and Parkinson's disease Progress in Neurobiology 2001 63 1 71 124 10.1016/s0301-0082(00)00014-9 2-s2.0-0035239020 11040419 source
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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationMany studies have shown that Akkermansia can effectively improve symptoms in mouse models of ALS, progeria, and chronic colitis by promoting healing and recovery of intestinal mucosal layer and reducing the expression of proinflammatory cytokines such as TNF-α and IFN-γ in the colon.
“Many studies have shown that Akkermansia can effectively improve symptoms in mouse models of diseases such as ALS [34], progeria [35], and chronic colitis [36] by promoting healing and recovery of intestinal mucosal layer and reducing the expression of proinflammatory cytokines such as TNF-α and interferon gamma (IFN-γ) in the colon.”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [34] Blacher E. Bashiardes S. Shapiro H. Potential roles of gut microbiome and metabolites in modulating ALS in mice Nature 2019 572 7770 474 480 10.1038/s41586-019-1443-5 2-s2.0-85070805768 31330533 source
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- cites [35] Bárcena C. Valdés-Mas R. Mayoral P. Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice Nature Medicine 2019 25 8 1234 1242 10.1038/s41591-019-0504-5 2-s2.0-85070235329 31332389 source
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- cites [36] Collado M. C. Derrien M. Isolauri E. de Vos W. M. Salminen S. Intestinal integrity and Akkermansia muciniphila, a mucin-degrading member of the intestinal microbiota present in infants, adults, and the elderly Applied and Environmental Microbiology 2007 73 23 7767 7770 10.1128/aem.01477-07 2-s2.0-38449104720 17933936 PMC2168041 source
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May combine two claims.
Interpretationown dataCeftriaxone regulates the intestinal microbiota of PD mice and alleviates the motor dysfunction and decreased exploratory ability.
“We conclude that ceftriaxone regulates the intestinal microbiota of PD mice and alleviates the motor dysfunction and decreased exploratory ability.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationProinflammatory cytokines could play a role in the nonmotor symptoms of PD.
“proinflammatory cytokines could play a role in the nonmotor symptoms of PD [42]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [42] Lindqvist D. Kaufman E. Brundin L. Hall S. Surova Y. Hansson O. Non-motor symptoms in patients with Parkinson's disease - correlations with inflammatory cytokines in serum PLoS One 2012 7 10, article e47387 10.1371/journal.pone.0047387 2-s2.0-84867629199 23082161 PMC3474801 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationKnockout of the Tlr4 gene reduces rotenone-induced motor dysfunction, neuroinflammation, and corresponding neuropathological changes in PD mice.
“knockout of the Tlr4 gene reduces rotenone-induced motor dysfunction, neuroinflammation, and corresponding neuropathological changes in PD mice [33]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [33] Perez-Pardo P. Dodiya H. B. Engen P. A. Role of TLR4 in the gut-brain axis in Parkinson's disease: a translational study from men to mice Gut 2019 68 5 829 843 10.1136/gutjnl-2018-316844 2-s2.0-85058680684 30554160 source
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May combine two claims.
PremisecitationWhen brain tissue is damaged or stimulated by α-syn or bacteria and their metabolites in the brain, TLR4 is activated on microglia, and then the NF-κB pathway is activated to promote the secretion of proinflammatory factors such as IL-6, IL-1β, and TNF-α; the ultimate outcome is the death of neurons.
“When brain tissue is damaged or stimulated by α-syn or bacteria and their metabolites in the brain, TLR4 is activated on microglia, and then, the NF-κB pathway is activated to promote the secretion of proinflammatory factors such as IL-6, IL-1β, and TNF-α; the ultimate outcome is the death of neurons [30, 32].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [30] Colonna M. Butovsky O. Microglia function in the central nervous system during health and neurodegeneration Annual Review of Immunology 2017 35 1 441 468 10.1146/annurev-immunol-051116-052358 2-s2.0-85018340947 28226226 PMC8167938 source
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- cites [32] Voet S. Srinivasan S. Lamkanfi M. van Loo G. Inflammasomes in neuroinflammatory and neurodegenerative diseases EMBO Molecular Medicine 2019 11 6 10.15252/emmm.201810248 2-s2.0-85064631879 31015277 PMC6554670 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationNeuroinflammation is characterised by the activation of microglia and astrocytes.
“Neuroinflammation is characterised by the activation of microglia and astrocytes [29].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [29] Dutta G. Zhang P. Liu B. The lipopolysaccharide Parkinson's disease animal model: mechanistic studies and drug discovery Fundamental & Clinical Pharmacology 2008 22 5 453 464 10.1111/j.1472-8206.2008.00616.x 2-s2.0-52449115580 18710400 PMC2632601 source
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Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationMicroglia are the inherent immune effector cells in the central nervous system.
“Microglia is the inherent immune effector cells in the central nervous system [30, 31].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [30] Colonna M. Butovsky O. Microglia function in the central nervous system during health and neurodegeneration Annual Review of Immunology 2017 35 1 441 468 10.1146/annurev-immunol-051116-052358 2-s2.0-85018340947 28226226 PMC8167938 source
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- cites [31] White J. R. Dauros-Singorenko P. Hong J. Vanholsbeeck F. Phillips A. Swift S. The role of host molecules in communication with the resident and pathogenic microbiota: a review Medicine in Microecology 2020 4, article 100005 10.1016/j.medmic.2020.100005 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationStudies have shown that Lactobacillus acidophilus and Bifidobacterium infantis can improve abdominal pain and bloating in PD patients.
“studies have shown that Lactobacillus acidophilus and Bifidobacterium infantis can improve abdominal pain and bloating in PD patients [40]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [40] Georgescu D. Ancusa O. E. Georgescu L. A. Ionita I. Reisz D. Nonmotor gastrointestinal disorders in older patients with Parkinson's disease: is there hope? Clinical Interventions in Aging 2016 Volume 11 1601 1608 10.2147/cia.s106284 2-s2.0-84995545694 27956826 PMC5113937 source
Not checked in the free run.
The paper relies on this without support.
Little work has been done to explore ceftriaxone's potential mechanisms of adjusting intestinal microorganisms in PD.
“Although ceftriaxone has been used commonly in the clinic, little work has been done to explore its potential mechanisms of adjusting intestinal microorganisms in PD.”
The paper relies on this without support.
Little work has been done to explore the effect of ceftriaxone on the intestinal microbiota in PD.
“However, little work has been done to explore the effect of ceftriaxone on the intestinal microbiota in PD.”
The paper relies on this without support.
The neuroinflammatory response is involved in the pathogenesis of PD.
“In recent years, increasing evidence has confirmed that the neuroinflammatory response is involved in the pathogenesis of PD.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Compared to MPTP-treated mice, mice receiving fecal microbiota from healthy human controls showed less loss of TH+ neurons.
“However, compared to MPTP-treated mice, the mice receiving fecal microbiota from healthy human controls showed less loss of TH+ neurons, consistent with previous reports [18, 49].”
From Healthy Human Fecal Microbiota Transplantation into Mice Attenuates MPTP-Induced Neurotoxicity <i>via</i> AMPK/SOD2 Pathway (2023) · cites this paper as [49]
Intraperitoneal injection of MPTP can induce marked gut dysbacteriosis.
“intraperitoneal injection of MPTP can induce marked gut dysbacteriosis [33, 49, 71]”
From Healthy Human Fecal Microbiota Transplantation into Mice Attenuates MPTP-Induced Neurotoxicity <i>via</i> AMPK/SOD2 Pathway (2023) · cites this paper as [49]
Abundance of Akkermansia in PD substantially decreased.
“Both the data presented by Petrov et al. [71] and our own analysis show that the abundance of Akkermansia in PD substantially decreased.”
From Neuroprotective Effects of Bifidobacterium breve CCFM1067 in MPTP-Induced Mouse Models of Parkinson’s Disease (2022) · cites this paper as [71]
Both mice and patients with Parkinson's disease exhibit increased levels of the genus Akkermansia.
“Both mice and patients with PD exhibit increased levels of the genus Akkermansia [51,52].”
From Neuroprotective Effects of Sodium Butyrate by Restoring Gut Microbiota and Inhibiting TLR4 Signaling in Mice with MPTP-Induced Parkinson’s Disease (2023) · cites this paper as [51]
CTX treatment increases relative abundance of Akkermansia species in MPTP-induced PD mice.
“in vivo, there is evidence that CTX treatment modifies the GM composition of MPTP-induced PD mice by disadvantaging the growth of Proteus while increasing the relative abundance of Akkermansia species, which act as probiotics when their SCFAs-converting activity exceeds that of intestinal barrier degradation (see also Section 2.1 Gut microbiota dysregulation in PD) [232].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [232]
Akkermansia species act as probiotics when their SCFAs-converting activity exceeds that of intestinal barrier degradation.
“in vivo, there is evidence that CTX treatment modifies the GM composition of MPTP-induced PD mice by disadvantaging the growth of Proteus while increasing the relative abundance of Akkermansia species, which act as probiotics when their SCFAs-converting activity exceeds that of intestinal barrier degradation (see also Section 2.1 Gut microbiota dysregulation in PD) [232].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [232]
CTX reduces TLR-4, MyD88, and NF-κB in the colon.
“Further studies proved the ability of CTX to reduce the levels of the main pro-inflammatory mediators TLR-4, MyD88 (myeloid differentiation primary response 88), IL-1β, TNF-α and NF-κB in the brain, TLR-4, MyD88, and NF-κB in the colon and IL-1β, TNF-α and IL-6 in the serum [232,233,234].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [232]
CTX treatment disadvantages growth of Proteus in MPTP-induced PD mice.
“in vivo, there is evidence that CTX treatment modifies the GM composition of MPTP-induced PD mice by disadvantaging the growth of Proteus while increasing the relative abundance of Akkermansia species, which act as probiotics when their SCFAs-converting activity exceeds that of intestinal barrier degradation (see also Section 2.1 Gut microbiota dysregulation in PD) [232].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [232]
CTX treatment modifies GM composition of MPTP-induced PD mice.
“in vivo, there is evidence that CTX treatment modifies the GM composition of MPTP-induced PD mice by disadvantaging the growth of Proteus while increasing the relative abundance of Akkermansia species, which act as probiotics when their SCFAs-converting activity exceeds that of intestinal barrier degradation (see also Section 2.1 Gut microbiota dysregulation in PD) [232].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [232]
CTX administration reduces GFAP expression.
“In line with these data, CTX administration was associated with reduced glial fibrillary acid protein (GFAP) and ionized calcium-binding adapter molecule 1 (IBA-1) expression, two markers of astrogliosis and microglia activation, respectively [232,235,236,237].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [232]
CTX reduces TLR-4, MyD88, IL-1β, TNF-α and NF-κB in the brain.
“Further studies proved the ability of CTX to reduce the levels of the main pro-inflammatory mediators TLR-4, MyD88 (myeloid differentiation primary response 88), IL-1β, TNF-α and NF-κB in the brain, TLR-4, MyD88, and NF-κB in the colon and IL-1β, TNF-α and IL-6 in the serum [232,233,234].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [232]
CTX reduces IL-1β, TNF-α and IL-6 in the serum.
“Further studies proved the ability of CTX to reduce the levels of the main pro-inflammatory mediators TLR-4, MyD88 (myeloid differentiation primary response 88), IL-1β, TNF-α and NF-κB in the brain, TLR-4, MyD88, and NF-κB in the colon and IL-1β, TNF-α and IL-6 in the serum [232,233,234].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [232]
CTX administration reduces IBA-1 expression.
“In line with these data, CTX administration was associated with reduced glial fibrillary acid protein (GFAP) and ionized calcium-binding adapter molecule 1 (IBA-1) expression, two markers of astrogliosis and microglia activation, respectively [232,235,236,237].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [232]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Conflicting sequencing platforms in the methods
MajorThe DNA extraction section says the PCR products were sequenced on a HiSeq 2000, whereas the sequencing analysis section says a MiSeq/NovaSeq platform was used for paired-end sequencing. The methods do not explain whether these refer to separate sequencing runs.
“Then, the polymerase chain reaction (PCR) products were sequenced on the IlluminaHiSeq 2000 platform (Illumina, Inc.) (GenBank accession number PRJNA659569).”
“The Illumina MiSeq/NovaSeq platform was used to conduct paired-end sequencing of community DNA fragments.”
Conflicting accounts of MPTP's effect on microbiota α-diversity
MajorThe Results say the Chao1 and Faith_pd indices showed no obvious difference between the control and MPTP groups, while the Discussion says those indices showed that MPTP reduced α-diversity.
“The Chao1 index and Faith_pd index showed that there was no obvious difference between the C and M groups”
“Through the Chao1 index and Faith_pd index, we found that MPTP treatment reduced the α-diversity of the intestinal microbiota.”
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Varesi, A., Campagnoli, L. I. M., Fahmideh, F., Pierella, E., Romeo, M., Ricevuti, G., Nicoletta, M., Chirumbolo, S., & Pascale, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232012289 · Cited by 88 · see citing works
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- Authors
- Zhou, X., Lu, J., Wei, K., Wei, J., Tian, P., Yue, M., Wang, Y., Hong, D., Li, F., Wang, B., Chen, T., & Fang, X.
- Affiliations
- First Affiliated Hospital of Nanchang University (CN)
- Nanchang University (CN)
- Corresponding author
- Chen, Tingtao
- Fang, Xin
- ORCID
- Venue
- Oxidative Medicine and Cellular Longevity
- Publisher
- Wiley
- Published
- 2021-01
- Volume
- 2021
- Issue
- 1
- Pages
- 9424582-9424582
- ISSN
- 1942-0994 (ISSN-L)
- 1942-0900
- PMC
- PMC8687851
- OpenAlex
- W4200025659
- Semantic Scholar
- 91b26199ff7a65f7a7af8060847477f8be75166e
- Cited by
- 85
- References
- 42
- Citations by year
- 2026: 11 · 2025: 19 · 2024: 34 · 2023: 16 · 2022: 4 · 2019: 1
- FWCI
- 8.01
- Type
- journal article
- Language
- en
- Update notices
- correction (2026-02-18)
- Open access
- hybrid
- doi.org
- Locations
- Oxidative Medicine and Cellular Longevity (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (82060222, 82060638)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, MPTP-induced neurotoxicity, neuroprotection, neuroinflammation, gut microbiota, gut-brain axis, TLR4, MyD88, NF-κB signaling, Akkermansia, Proteus, tight junction proteins, intestinal permeability, astroglia, microglia
- MeSH terms
- Gastrointestinal Microbiome, Neuroinflammatory Diseases, Animals, Anti-Bacterial Agents, Ceftriaxone, Disease Models, Animal, Intestinal Mucosa, Male, Mice, Inbred C57BL, Neurotoxins, Parkinson Disease, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Neuroprotective Agents, Mice
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