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Neuroprotective effects of short-chain fatty acids in MPTP induced mice model of Parkinson's disease
Abstract
Gut microbial metabolites, SCFAs, were related with the occurrence and development of Parkinson's disease (PD). But the effects of different short-chain fatty acids (SCFAs) on PD and involving mechanisms are still undefined. In this study we evaluate the effects of three dominant SCFAs (acetate, propionate and butyrate) on motor damage, dopaminergic neuronal degeneration and underlying neuroinflammation related mechanisms in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice. High (2.0 g/kg) or low doses (0.2 g/kg) of sodium acetate (NaA), sodium propionate (NaP) or sodium butyrate (NaB) were gavaged into PD mice for 6 weeks. High doses of NaA reduced the turning time of PD mice. NaB significantly reduced the turning and total time in pole test, and increased the average velocity in open field test when compared with PD mice, indicating the most effective alleviation of PD-induced motor disorder. Low and high doses of NaB significantly increased the content of tyrosine hydroxylase (TH) by 12.3% and 20.2%, while reduced α-synuclein activation by 159.4% and 132.7% in the substantia nigra pars compacta (SNpc), compared with PD groups. Butyrate reached into the midbrain SNpc and suppressed microglia over-activation. It inhibited the levels of pro-inflammatory factors (IL-6, IL-1β and TNF-α) (P < 0.01) and iNOS. Besides, butyrate inhibited the activation of NF-κB and MAPK signaling pathways in the SNpc region. Consequently, sodium butyrate could inhibit neuroinflammation and alleviate neurological damage of PD.
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“Additionally, studies have demonstrated the neuroprotective effects of sodium butyrate in MPTP-induced PD mice by attenuating microglial reactivity via the inhibition of TLR4/MyD88/NF-κB and MAPK signaling pathway.319–321”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [319]
In the citing paper
“NaB can improve motor symptoms, neuronal loss, and neuroinflammation in MPTP-induced PD mice [23,24,25].”
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 [23]
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Cites
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The role of short-chain fatty acids in microbiota–gut–brain communication
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Items 101–101 of 101
Wang, W., Sun, W., Ma, L., Xu, M., & Dong, X. (2026) · Frontiers in Neurology · doi:10.3389/fneur.2026.1889517
Metadata
- Authors
- Hou, Y., Li, X., Liu, C., Zhang, M., Zhang, X., Ge, S., & Zhao, L.
- Affiliations
- Beijing Advanced Innovation Center for Food Nutrition and Human Health (CN)
- China Agricultural University (CN)
- Beijing Technology and Business University (CN)
- Corresponding author
- Zhao, Liang
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2021-07
- Volume
- 150
- Pages
- 111376
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W3159598422
- Cited by
- 101
- References
- 63
- Citations by year
- 2026: 16 · 2025: 24 · 2024: 28 · 2023: 15 · 2022: 13 · 2021: 5
- FWCI
- 7.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (32072196)
- Beijing Science and Technology Planning Project (Z181100009318005)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- short-chain fatty acids, Parkinson's disease, MPTP-induced neurotoxicity, sodium butyrate, sodium acetate, sodium propionate, neuroprotection, dopaminergic neuron loss, substantia nigra pars compacta, neuroinflammation, microglial activation, alpha-synuclein, tyrosine hydroxylase, NF-κB signaling, MAPK signaling, gut microbiota metabolites, motor impairment
- MeSH terms
- Animals, Disease Models, Animal, Fatty Acids, Volatile, Mice, Inbred C57BL, Parkinson Disease, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Neuroprotective Agents, MPTP Poisoning, Mice, Dopaminergic Neurons
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