Sodium butyrate improves locomotor impairment and early mortality in a rotenone-induced Drosophila model of Parkinson's disease
Open accessAbstract
Parkinson's disease (PD) is a neurodegenerative disorder primarily affecting the dopaminergic neurons in the nigrastriatal pathway resulting in debilitating motor impairment in both familial and sporadic cases. Histone deacetylase (HDAC) inhibitors have been recently implicated as a therapeutic candidate because of their ability to correct the disrupted HDAC activity in PD and other neurodegenerative diseases. Sodium butyrate (SB), an HDAC inhibitor, reduces degeneration of dopaminergic neurons in a mutant alpha-synuclein Drosophila transgenic model of familial PD. Chronic exposure to the pesticide rotenone also causes selective degeneration of dopaminergic neurons and causes locomotor impairment and early mortality in a Drosophila model of chemically induced PD. This study investigated the effects of sodium butyrate on locomotor impairment and early mortality in a rotenone-induced PD model. We show that treatment with 10mM SB-supplemented food rescued the rotenone-induced locomotor impairment and early mortality in flies. Additionally, flies with the genetic knockdown of HDAC activity through Sin3A loss-of-function mutation (Sin3A(lof)) were resistant to rotenone-induced locomotor impairment and early mortality. Furthermore, SB-supplemented Sin3A(lof) flies had a modest additive effect for improving locomotor impairment. We also show SB-mediated improvement of rotenone-induced locomotor impairment was associated with elevated dopamine levels in the brain. However, the possibility of SB-mediated protective role through mechanisms independent from dopamine system is also discussed. These findings demonstrate that HDAC inhibitors like SB can ameliorate locomotor impairment in a rotenone-induced PD model.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
SCFAs can reduce degeneration of dopaminergic neurons and improve dyskinesia in a rotenone-induced Drosophila Parkinson's disease model.
“SCFAs may be able to modulate neuroinflammation in (HDACi), can reduce the degeneration of dopaminergic neurons and improve dyskinesia in a rotenone-induced Drosophila Parkinson's disease model.194”
From The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options (2021) · cites this paper as [194]
The Abstract and Discussion (pages unavailable) report that sodium butyrate improved rotenone-induced locomotor impairment in Drosophila and was associated with higher brain dopamine levels. They do not report reduced dopaminergic-neuron degeneration in the rotenone model; the Abstract attributes that effect to sodium butyrate in a different, α-synuclein Drosophila model. The study also tested sodium butyrate, not SCFAs as a group, and measured locomotor impairment rather than dyskinesia. (LLM, conf=0.89)
Experimental — accuracy not yet measuredFMT from healthy donors and butyrate administration in animal models of PD improves motor impairment and dopamine deficiency.
“Supporting this hypothesis, growing evidence has shown that FMT from healthy donors (171) as well as butyrate administration in animal models of PD improves motor impairment and dopamine deficiency (172–175).”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [174]
Sodium butyrate treatment ameliorates motor symptoms in a Drosophila rotenone-induced Parkinson's disease model.
“The NaB treatment ameliorates motor symptoms in a Drosophila rotenone-induced PD model [43].”
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 [43]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A Drosophila model of Parkinson's disease
Feany, M., & Bender, W. (2000) · Nature · doi:10.1038/35006074 · Cited by 2,145 · see citing works
Suppression of Oxidative Stress by β-Hydroxybutyrate, an Endogenous Histone Deacetylase Inhibitor
Shimazu, T., Hirschey, M. D., Newman, J., He, W., Shirakawa, K., Le Moan, N., Grueter, C. A., Lim, H., Saunders, L. R., Stevens, R. D., et al. (2013) · Science · doi:10.1126/science.1227166 · Cited by 1,777 · see citing works
ETIOLOGY AND PATHOGENESIS OF PARKINSON'S DISEASE
Olanow, C. W., & Tatton, W. G. (1999) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.22.1.123 · Cited by 1,394 · see citing works
Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila
Steffan, J. S., Bodai, L., Pallos, J., Poelman, M., McCampbell, A., Apostol, B. L., Kazantsev, A., Schmidt, E., Zhu, Y.-Z., Greenwald, M., et al. (2001) · Nature · doi:10.1038/35099568 · Cited by 1,228 · see citing works
Mechanism of Toxicity in Rotenone Models of Parkinson's Disease
Sherer, T., Betarbet, R. S., Testa, C. M., Seo, B. B., Richardson, J. R., Kim, J. H., Miller, G. W., Yagi, T., Matsuno‐Yagi, A., & Greenamyre, J. T. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-34-10756.2003 · Cited by 1,073 · see citing works
A highly reproducible rotenone model of Parkinson's disease
Cannon, J. R., Tapias, V., Na, H. M., Honick, A. S., Drolet, R. E., & Greenamyre, J. T. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.01.016 · Cited by 802 · see citing works
Ferrante, R. J., Kubilus, J. K., Lee, J.-H., Ryu, H., Beesen, A. A., Zucker, B., Smith, K., Kowall, N. W., Ratan, R. R., Luthi‐Carter, R., et al. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-28-09418.2003 · Cited by 694 · see citing works
Multiple roles of HDAC inhibition in neurodegenerative conditions
Chuang, D.-M., Leng, Y., Marinova, Z., Kim, H.-J., & Chiu, C.-T. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.06.002 · Cited by 676 · see citing works
α-synuclein acts in the nucleus to inhibit histone acetylation and promote neurotoxicity
Kontopoulos, E., Parvin, J. D., & Feany, M. Β. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl243 · Cited by 539 · see citing works
Sun, J., & Tower, J. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.1.216 · Cited by 467 · see citing works
HATs and HDACs in neurodegeneration: a tale of disconcerted acetylation homeostasis
Saha, R. N., & Pahan, K. (2005) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401769 · Cited by 439 · see citing works
Chronic Exposure to Rotenone Models Sporadic Parkinson's Disease in Drosophila melanogaster
Coulom, H., & Birman, S. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.2993-04.2004 · Cited by 425 · see citing works
Wu, X., Chen, P. S., Dallas, S., Wilson, B. C., Block, M. L., Wang, C.-C., Kinyamu, H. K., Lu, N. Z., Gao, X., Leng, Y., et al. (2008) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145708009024 · Cited by 314 · see citing works
Cicchetti, F., Drouin‐Ouellet, J., & Gross, R. E. (2009) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2009.06.005 · Cited by 312 · see citing works
Testa, C. M., Sherer, T., & Greenamyre, J. T. (2005) · Molecular Brain Research · doi:10.1016/j.molbrainres.2004.11.007 · Cited by 296 · see citing works
Pallos, J., Bodai, L., Lukácsovich, T., Purcell, J. M., Steffan, J. S., Thompson, L. M., & Marsh, J. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn273 · Cited by 265 · see citing works
Levodopa in the treatment of Parkinson’s disease: an old drug still going strong
Antonini, A. (2010) · Clinical Interventions in Aging · doi:10.2147/cia.s6456 · Cited by 251 · see citing works
Lewis, E. J., Tank, A. W., Weiner, N., & Chikaraishi, D. M. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)43909-3 · Cited by 242 · see citing works
Egorin, M. J., Yuan, Z.-M., Sentz, D. L., Plaisance, K. I., & Eiseman, J. L. (1999) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s002800050922 · Cited by 166 · see citing works
Physiological Roles of Class I HDAC Complex and Histone Demethylase
Hayakawa, T., & Nakayama, J. (2010) · BioMed Research International · doi:10.1155/2011/129383 · Cited by 165 · see citing works
Haque, M. E., Asanuma, M., Higashi, Y., Miyazaki, I., Tanaka, K.-I., & Ogawa, N. (2002) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/s0304-4165(02)00440-3 · Cited by 151 · see citing works
Isolation and characterization of the gene for drosophila tyrosine hydroxylase
Neckameyer, W. S., & Quinn, W. G. (1989) · Neuron · doi:10.1016/0896-6273(89)90183-9 · Cited by 137 · see citing works
Stereotaxical Infusion of Rotenone: A Reliable Rodent Model for Parkinson's Disease
Xiong, N., Huang, J., Zhang, Z., Zhang, Z., Xiong, J., Liu, X., Jia, M., Wang, F., Chen, C., Cao, X., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007878 · Cited by 119 · see citing works
Thanvi, B., Lo, N., & Robinson, T. (2007) · Postgraduate medical journal · doi:10.1136/pgmj.2006.054759 · Cited by 116 · see citing works
Protection of dopaminergic cells from MPP+-mediated toxicity by histone deacetylase inhibition
Kidd, S. K., & Schneider, J. S. (2010) · Brain Research · doi:10.1016/j.brainres.2010.07.041 · Cited by 113 · see citing works
Kidd, S. K., & Schneider, J. S. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.08.010 · Cited by 94 · see citing works
Toxin-Induced and Genetic Animal Models of Parkinson's Disease
Hisahara, S., & Shimohama, S. (2010) · Parkinson s Disease · doi:10.4061/2011/951709 · Cited by 91 · see citing works
Hosamani, R., Ramesh, S. R., & ., M. (2010) · Neurochemical Research · doi:10.1007/s11064-010-0198-z · Cited by 87 · see citing works
Histone Deacetylase Inhibitors and Neurodegenerative Disorders: Holding the Promise
Mai, A., Rotili, D., Valente, S., & Kazantsev, A. G. (2009) · Current Pharmaceutical Design · doi:10.2174/138161209789649349 · Cited by 78 · see citing works
Bayersdorfer, F., Voigt, A., Schneuwly, S., & Botella, J. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.02.012 · Cited by 74 · see citing works
Spivey, A. (2011) · Environmental Health Perspectives · doi:10.1289/ehp.119-a259a · Cited by 71 · see citing works
Age-Environment and Gene-Environment Interactions in the Pathogenesis of Parkinson's Disease
Couteur, D. G. L., Müller, M., Yang, M., et al. (2002) · Reviews on Environmental Health · doi:10.1515/reveh.2002.17.1.51 · Cited by 63 · see citing works
D’Souza, A., Onem, E., Patel, P., Gamma, E. F. L., & Nankova, B. B. (2008) · Brain Research · doi:10.1016/j.brainres.2008.09.088 · Cited by 48 · see citing works
Genetic Distortion of the Balance between Punishment and Relief Learning in Drosophila
Yarali, A., Krischke, M., Michels, B., et al. (2008) · Journal of Neurogenetics · doi:10.1080/01677060802441372 · Cited by 40 · see citing works
Chemical regulation of mid- and late-life longevities in Drosophila
McDonald, P. J., Maizi, B. M., & Arking, R. (2012) · Experimental Gerontology · doi:10.1016/j.exger.2012.09.006 · Cited by 35 · see citing works
Regulation of the tyrosine hydroxylase gene promoter by histone deacetylase inhibitors
Kim, H.-S., Park, J., Hong, S.-J., et al. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.11.012 · Cited by 31 · see citing works
Haque, M. E., Asanuma, M., Higashi, Y., Miyazaki, I., Tanaka, K.-I., & Ogawa, N. (2003) · Neuroscience Research · doi:10.1016/s0168-0102(03)00166-4 · Cited by 25 · see citing works
Nankova, B. B., Chua, J., Mishra, R., Kobasiuk, C. D., & Gamma, E. F. L. (2003) · Pediatric Research · doi:10.1203/00006450-200301000-00019 · Cited by 22 · see citing works
Akiba, Y., Cave, J. W., Akiba, N., et al. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.02.054 · Cited by 13 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Tabachnick BG Fidell LS 2007 Experimental Design Using ANOVA Belmont Duxbury Press
Cited by
Sorted by citations
The role of short-chain fatty acids in microbiota–gut–brain communication
Dalile, B., Van Oudenhove, L., Vervliet, B., & Verbeke, K. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0157-3 · Cited by 3,357 · see citing works
The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication
Silva, Y. P., Bernardi, A., & Frozza, R. L. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00025 · Cited by 3,043 · see citing works
Unger, M. M., Spiegel, J., Dillmann, K.-U., Grundmann, D., Philippeit, H., Bürmann, J., Faßbender, K., Schwiertz, A., & Schäfer, K.-H. (2016) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2016.08.019 · Cited by 1,159 · see citing works
Hill‐Burns, E. M., Debelius, J. W., Morton, J. T., Wissemann, W. T., Lewis, M. R., Wallen, Z. D., Peddada, S. D., Factor, S. A., Molho, E., Zabetian, C. P., et al. (2017) · Movement Disorders · doi:10.1002/mds.26942 · Cited by 874 · see citing works
The epigenetics of aging and neurodegeneration
Lardenoije, R., Iatrou, A., Kenis, G., Kompotis, K., Steinbusch, H. W. M., Mastroeni, D., Coleman, P., Lemere, C. A., Hof, P. R., van den Hove, D. L. A., et al. (2015) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.05.002 · Cited by 381 · see citing works
<scp>Meta‐Analysis</scp> of Gut Dysbiosis in Parkinson's Disease
Nishiwaki, H., Ito, M., Ishida, T., Hamaguchi, T., Maeda, T., Kashihara, K., Tsuboi, Y., Ueyama, J., Shimamura, T., Mori, H., et al. (2020) · Movement Disorders · doi:10.1002/mds.28119 · Cited by 370 · see citing works
The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options
Wang, Q., Luo, Y., Ray Chaudhuri, K., Reynolds, R., Tan, E.-K., & Pettersson, S. (2021) · Brain · doi:10.1093/brain/awab156 · Cited by 281 · see citing works
Liu, J., Wang, F., Liu, S., Du, J., Hu, X., Xiong, J., Fang, R., Chen, W., & Sun, J. (2017) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2017.08.3235 · Cited by 218 · see citing works
The function of gut microbiota in immune-related neurological disorders: a review
Sittipo, P., Choi, J., Lee, S., & Lee, Y. K. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02510-1 · Cited by 221 · see citing works
Srivastav, S., Neupane, S., Bhurtel, S., Katila, N., Maharjan, S., Choi, H., Hong, J. T., & Choi, D.-Y. (2019) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2019.03.021 · Cited by 212 · see citing works
Sharma, S., Taliyan, R., & Singh, S. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.05.052 · Cited by 142 · see citing works
Nishiwaki, H., Hamaguchi, T., Ito, M., Ishida, T., Maeda, T., Kashihara, K., Tsuboi, Y., Ueyama, J., Shimamura, T., Mori, H., et al. (2020) · mSystems · doi:10.1128/msystems.00797-20 · Cited by 133 · see citing works
Neuroprotective effects of short-chain fatty acids in MPTP induced mice model of Parkinson's disease
Hou, Y., Li, X., Liu, C., Zhang, M., Zhang, X., Ge, S., & Zhao, L. (2021) · Experimental Gerontology · doi:10.1016/j.exger.2021.111376 · Cited by 101 · see citing works
Potential roles of gut microbiota and microbial metabolites in Parkinson’s disease
Zheng, S.-Y., Li, H.-X., Xu, R.-C., Miao, W.-T., Dai, M.-Y., Ding, S.-T., & Liu, H.-D. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101347 · Cited by 101 · see citing works
HDAC inhibitors: A new promising drug class in anti-aging research
Pasyukova, E. G., & Vaiserman, A. M. (2017) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.08.008 · Cited by 99 · see citing works
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
Yang, X., Ai, P., He, X., Mo, C., Zhang, Y., Xu, S., Lai, Y., Qian, Y., & Xiao, Q. (2022) · Movement Disorders · doi:10.1002/mds.29063 · Cited by 82 · see citing works
Guo, T.-T., Zhang, Z., Sun, Y., Zhu, R.-Y., Wang, F.-X., Ma, L.-J., Jiang, L., & Liu, H.-D. (2023) · Nutrients · doi:10.3390/nu15040930 · Cited by 82 · see citing works
Role of histone deacetylases and their inhibitors in neurological diseases
Zhang, L.-Y., Zhang, S.-Y., Wen, R., Zhang, T.-N., & Yang, N. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107410 · Cited by 84 · see citing works
Manjunath, M. J., & Muralidhara (2015) · Journal of Food Science and Technology · doi:10.1007/s13197-013-1219-0 · Cited by 69 · see citing works
Lorente-Picón, M., & Laguna, A. (2021) · Biomolecules · doi:10.3390/biom11030433 · Cited by 69 · see citing works
Zhang, Y., Xu, S., Qian, Y., He, X., Mo, C., Yang, X., & Xiao, Q. (2022) · Brain Research · doi:10.1016/j.brainres.2021.147749 · Cited by 34 · see citing works
- Authors
- St. Laurent, R., O’Brien, L. M., & Ahmad, S. T.
- Affiliations
- Colby College (US)
- Corresponding author
- Ahmad, S.T.
- ORCID
- O’Brien, L.M.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 246
- Pages
- 382-390
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC3721507
- OpenAlex
- W2032519397
- Cited by
- 199
- References
- 39
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 19 · 2023: 18 · 2022: 30 · 2021: 28 · 2020: 22 · 2019: 10 · 2018: 7 · 2017: 11 · 2016: 11 · 2015: 13 · 2014: 9 · 2013: 3
- FWCI
- 7.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Center for Research Resources
- INBRE (5P20RR016463-12)
- National Institutes of Health (8 P20 GM103423-12)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- Parkinson's disease, sodium butyrate, histone deacetylase inhibitors, rotenone, Drosophila model, locomotor impairment, early mortality, dopaminergic neuron loss, SIN3A, dopamine levels, neuroprotection
- MeSH terms
- Animals, Disease Models, Animal, Drosophila, Motor Activity, Parkinson Disease, Secondary, Pesticides, Rotenone, Butyric Acid, Animals, Genetically Modified, Histone Deacetylase Inhibitors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
