Rifampicin Decreases Neuroinflammation to Maintain Mitochondrial Function and Calcium Homeostasis in Rotenone-Treated Zebrafish
Abstract
Among the mechanisms underlying Parkinson's disease, many pathogenic mechanisms are suggested to be effective such as oxidative stress, mitochondrial dysfunction, disruption of the ubiquitin-proteasome system, and neuroinflammation. Calcium is very important for neuronal and glial cells, neurodegenerative disease mechanisms are closely related to disturbed calcium homeostasis. Recent studies strongly support the role of inflammation in nigrostriatal degeneration in PD. In recent years, Rifampicin, a macrocyclic antibiotic has been shown to have a protective effect on neurons. This study aims to evaluate the effects of rifampicin in the experimental PD model induced by rotenone in zebrafish focusing on the relationship between calcium-dependent mitochondrial dysfunction and inflammation. Adult zebrafish were exposed to rotenone and rifampicin for 3 weeks. Locomotor activity was determined as the total distance that the zebrafish traveled for 5 min. Neuroinflammation and PD-related gene expressions were determined by RT-PCR. Mitochondrial calcium levels were determined using inductively coupled plasma-optical emission spectrometry (ICP-OES). Gamma synuclein, Park 7, Sigma-1 receptor expressions were determined by Western Blot. Our results show that rifampicin may be effective in reducing neuroinflammation, which may be an effective strategy to reduce mitochondrial dysfunction due to impaired calcium homeostasis in PD.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Rotenone-induced PD in zebrafish benefits from rifampicin administration due to a decrease in neuroinflammation.
“More recently, rotenone-induced PD in zebrafish has shown benefit from rifampicin administration due to the decrease in neuroinflammation [299].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [299]
Cites
The Roles of PINK1, Parkin, and Mitochondrial Fidelity in Parkinson’s Disease
Pickrell, A. M., & Youle, R. J. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.007 · Cited by 2,310 · see citing works
Hayashi, T., & Su, T.-P. (2007) · Cell · doi:10.1016/j.cell.2007.08.036 · Cited by 1,826 · 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
VDAC, a multi-functional mitochondrial protein regulating cell life and death
Shoshan‐Barmatz, V., Pinto, V. D., Zweckstetter, M., Raviv, Z., Keinan, N., & Arbel, N. (2010) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2010.03.002 · Cited by 792 · see citing works
Toxin-induced models of Parkinson’s disease
Bové, J., Prou, D., Perier, C., & Przedborski, S. (2005) · NeuroRX · doi:10.1602/neurorx.2.3.484 · Cited by 739 · see citing works
Ding, W.-X., Ni, H., Li, M., Liao, Y., Chen, X., Stolz, D. B., Dorn, G. W., & Yin, X. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.119537 · Cited by 586 · see citing works
p62/SQSTM1 cooperates with Parkin for perinuclear clustering of depolarized mitochondria
Okatsu, K., Saisho, K., Shimanuki, M., Nakada, K., Shitara, H., Sou, Y., Kimura, M., Sato, S., Hattori, N., Komatsu, M., et al. (2010) · Genes to Cells · doi:10.1111/j.1365-2443.2010.01426.x · Cited by 397 · cited 2× · see citing works
“By accumulating in the outer membrane of the damaged mitochondria, PINK1 marks the damaged mitochondria for destruction (Ding et al. 2010, Okatsu et al. 2010).”
BackgroundJin, H., Kanthasamy, A., Ghosh, A., Anantharam, V., Kalyanaraman, B., & Kanthasamy, A. G. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.09.007 · Cited by 362 · see citing works
Targeting Alpha-Synuclein as a Therapy for Parkinson’s Disease
Fields, C. R., Bengoa‐Vergniory, N., & Wade‐Martins, R. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00299 · Cited by 336 · see citing works
Sensitivity of zebrafish to environmental toxins implicated in Parkinson's disease
Bretaud, S., Lee, S., & Guo, S. (2004) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2004.06.014 · Cited by 306 · see citing works
Neuroinflammatory processes in Parkinson's disease
Hirsch, É. C., Hunot, S., & Hartmann, A. (2005) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2004.10.013 · Cited by 298 · see citing works
Wilson, J. M., Bunte, R. M., & Carty, A. J. (2009) · PubMed · Cited by 284 · see citing works
Molecular mechanisms of pesticide-induced neurotoxicity: Relevance to Parkinson's disease
Franco, R., Li, S., Rodríguez‐Rocha, H., Burns, M., & Panayiotidis, M. I. (2010) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2010.06.003 · Cited by 262 · see citing works
Parkin Deficiency Increases Vulnerability to Inflammation-Related Nigral Degeneration
Frank-Cannon, T. C., Tran, T. A. T., Ruhn, K. A., Martinez, T. N., Hong, J. J., Marvin, M. A., Hartley, M., Treviño, I., O’Brien, D. E., Casey, B. H., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.3001-08.2008 · Cited by 262 · see citing works
Nitrated alpha‐synuclein‐activated microglial profiling for Parkinson’s disease
Reynolds, A. D., Glanzer, J. G., Kadiu, I., Ricardo-Dukelow, M., Chaudhuri, A., Ciborowski, P. S., Cerny, R. L., Gelman, B. B., Thomas, M. P., Mosley, R. L., et al. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.05087.x · Cited by 244 · see citing works
Sun, Y., Vashisht, A. A., Tchieu, J. H., Wohlschlegel, J. A., & Dreier, L. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.419721 · Cited by 244 · see citing works
Calcium, Bioenergetics, and Neuronal Vulnerability in Parkinson's Disease
Surmeier, D. J., & Schumacker, P. T. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r112.410530 · Cited by 233 · see citing works
Role of sigma-1 receptors in neurodegenerative diseases
Nguyen, L., Lucke-Wold, B. P., Mookerjee, S. A., Cavendish, J. Z., Robson, M. J., Scandinaro, A. L., & Matsumoto, R. R. (2014) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2014.12.005 · Cited by 231 · see citing works
Leonard, W. J., & Wan, C.-K. (2016) · F1000Research · doi:10.12688/f1000research.7634.1 · Cited by 184 · see citing works
Voltage‐dependent anion‐selective channel (VDAC) in the plasma membrane
Pinto, V. D., Messina, A. A., Lane, D. J. R., & Lawen, A. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.02.049 · Cited by 174 · see citing works
Alpha-Synuclein: From Early Synaptic Dysfunction to Neurodegeneration
Ghiglieri, V., Calabrese, V., & Calabresi, P. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00295 · Cited by 158 · see citing works
Helical α-Synuclein Forms Highly Conductive Ion Channels
Zakharov, L. N., Hulleman, J. D., Dutseva, E. A., Antonenko, Y. N., Rochet, J., & Cramer, W. A. (2007) · Biochemistry · doi:10.1021/bi701275p · Cited by 131 · see citing works
Parkinson’s disease-like motor and non-motor symptoms in rotenone-treated zebrafish
Wang, Y., Liu, W., Yang, J., Wang, F., Sima, Y., Zhong, Z., Wang, H., Hu, L., & Liu, C. (2016) · NeuroToxicology · doi:10.1016/j.neuro.2016.11.006 · Cited by 125 · see citing works
Omura, T., Kaneko, M., Okuma, Y., Matsubara, K., & Nomura, Y. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/239854 · Cited by 113 · see citing works
The Role of α‐Synuclein in Both Neuroprotection and Neurodegeneration
Sidhu, A., Wersinger, C., Moussa, C., & Vernier, P. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1332.016 · Cited by 110 · see citing works
Subcellular localization of VDAC in mitochondria and ER in the cerebellum
Shoshan‐Barmatz, V., Zalk, R., Gincel, D., & Vardi, N. (2004) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2004.02.009 · Cited by 109 · see citing works
de Sousa, S. C., Maciel, E. N., Vercesi, A. E., & Castilho, R. F. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00421-6 · Cited by 109 · see citing works
The involvement of the sigma-1 receptor in neurodegeneration and neurorestoration
Ruscher, K., & Wieloch, T. W. (2014) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2014.11.011 · Cited by 107 · see citing works
Transcriptional Factor NF- κ B as a Target for Therapy in Parkinson's Disease
Flood, P. M., Li, Q., Peterson, L. J., Zhang, F., Shi, J., Gao, H., & Hong, J. (2011) · Parkinson s Disease · doi:10.4061/2011/216298 · Cited by 103 · see citing works
Hypokinesia and Reduced Dopamine Levels in Zebrafish Lacking β- and γ1-Synucleins
Milanese, C., Sager, J. J., Bai, Q., Farrell, T. C., Cannon, J. R., Greenamyre, J. T., & Burton, E. A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.308312 · Cited by 92 · 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
Selective vulnerability in α-synucleinopathies
Alegre‐Abarrategui, J., Brimblecombe, K. R., Roberts, R. F., Velentza‐Almpani, E., Tilley, B. S., Bengoa‐Vergniory, N., & Proukakis, C. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02010-2 · Cited by 89 · see citing works
Identification of a nuclear protein that promotes NF-κB activation
Chen, D., Li, Z., Yang, Q., Zhang, J., Zhai, Z., & Shu, H. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.09.074 · Cited by 85 · see citing works
Wang, X.-J., & Xu, J.-X. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.11.041 · Cited by 73 · see citing works
Frei, B. B., & Richter, C. (1986) · FEBS Letters · doi:10.1016/0014-5793(86)81192-9 · Cited by 71 · see citing works
K+‐Dependent Na+/Ca2+ Exchangers in the Brain
Lytton, J., Li, X., Dong, H., et al. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb04765.x · Cited by 66 · see citing works
NF-κB in transplantation: friend or foe?
Tsoulfas, G., & Geller, D. A. (2001) · Transplant Infectious Disease · doi:10.1034/j.1399-3062.2001.30405.x · Cited by 66 · see citing works
Rifampicin Attenuates the MPTP-Induced Neurotoxicity in Mouse Brain
Oida, Y., Kitaichi, K., Nakayama, H., Ito, Y., Fujimoto, Y., Shimazawa, M., Nagai, H., & Hara, H. (2006) · Brain Research · doi:10.1016/j.brainres.2006.01.116 · Cited by 47 · see citing works
Rifampicin and Parkinson’s disease
Bi, W., Zhu, L., Jing, X., Liang, Y., & Tao, E. (2012) · Neurological Sciences · doi:10.1007/s10072-012-1156-0 · Cited by 46 · see citing works
Endolysosomal dysfunction in Parkinson's disease: Recent developments and future challenges
Kett, L. R., & Dauer, W. T. (2016) · Movement Disorders · doi:10.1002/mds.26797 · Cited by 42 · see citing works
Rotenone impairs oxidant/antioxidant balance both in brain and intestines in zebrafish
Ünal, İ., Üstündağ, Ü. V., Ateş, P. S., Eğilmezer, G., Alturfan, A. A., Yiğitbaşı, T., & Emekli‐Alturfan, E. (2018) · International Journal of Neuroscience · doi:10.1080/00207454.2018.1538141 · Cited by 42 · see citing works
Self-citationFishing for Parkinson’s Disease: A review of the literature
Ünal, İ., & Emekli‐Alturfan, E. (2019) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2019.01.015 · Cited by 25 · see citing works
Self-citationAlteration of Dynein Function Affects α-Synuclein Degradation via the Autophagosome-Lysosome Pathway
Li, D., Shi, J., Mao, C., Liu, S., Wang, J.-D., Chen, J., Wang, F., Yang, Y., Hu, W., Hu, L., et al. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms141224242 · Cited by 20 · see citing works
Sigma-1 receptor: a potential new target for Parkinson′s disease?
Francardo, V. (2014) · Neural Regeneration Research · doi:10.4103/1673-5374.145351 · Cited by 19 · see citing works
Choi, I.-Y., Lim, J. H., Kim, C., et al. (2013) · Experimental Neurobiology · doi:10.5607/en.2013.22.3.200 · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
- Authors
- Yurtsever, İ., Üstündağ, Ü. V., Ünal, İ., Ateş, P. S., & Emekli-Alturfan, E.
- Affiliations
- Istanbul Medipol University (TR)
- Marmara University (TR)
- Faculty of Dentistry, Department of Basic Medical Sciences, Marmara University
- Corresponding author
- Yurtsever, İlknur
- Venue
- Drug and Chemical Toxicology
- Publisher
- Informa UK Limited
- Published
- 2020-11-13
- Volume
- 45
- Issue
- 4
- Pages
- 1544-1551
- ISSN
- 0148-0545 (ISSN-L)
- 1525-6014
- OpenAlex
- W3104756285
- Cited by
- 39
- References
- 45
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 6 · 2023: 11 · 2022: 9 · 2021: 5
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drug and Chemical Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Dspace Repository (Marmara Üniversitesi) (submittedVersion)
- Funders
- Marmara University Scientific Research and Project Commission (SAG-C-DRP-241018-0572)
- 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
- rifampicin, Parkinson's disease, neuroinflammation, mitochondrial dysfunction, calcium homeostasis, rotenone, zebrafish, nigrostriatal degeneration, locomotor activity, gamma-synuclein, DJ-1, sigma-1 receptor, neuroprotection
- MeSH terms
- Neuroinflammatory Diseases, Animals, Calcium, Homeostasis, Inflammation, Mitochondria, Rifampin, Rotenone, Zebrafish, Oxidative Stress, Neurodegenerative Diseases
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