Minocycline Rescues from Zinc-Induced Nigrostriatal Dopaminergic Neurodegeneration: Biochemical and Molecular Interventions
Abstract
Accumulation of zinc (Zn) in dopaminergic neurons is implicated in Parkinson's disease (PD), and microglial activation plays a critical role in toxin-induced Parkinsonism. Oxidative stress is accused in Zn-induced dopaminergic neurodegeneration; however, its connection with microglial activation is still not known. This study was undertaken to elucidate the role and underlying mechanism of microglial activation in Zn-induced nigrostriatal dopaminergic neurodegeneration. Male Wistar rats were treated intraperitoneally with/without zinc sulphate (20 mg/kg) in the presence/absence of minocycline (30 mg/kg), a microglial activation inhibitor, for 2-12 weeks. While neurobehavioral and biochemical indexes of PD and number of dopaminergic neurons were reduced, the number of microglial cells was increased in the substantia nigra of the Zn-exposed animals. Similarly, Zn elevated lipid peroxidation (LPO) and activities of superoxide dismutase (SOD) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; however, catalase activity was reduced. Besides, Zn increased an association of NADPH oxidase subunit p67(phox) with membrane, cytochrome c release from the mitochondria and cleavage of pro-caspase 3. Zn attenuated the expression of tyrosine hydroxylase (TH) and vesicular monoamine transporter-2 (VMAT-2) while augmented the expression of dopamine transporter (DAT) and heme oxygenase-1 (HO-1). Minocycline alleviated Zn-induced behavioural impairments, loss of TH-positive neurons, activated microglial cells and biochemical indexes and modulated the expression of studied genes/proteins towards normalcy. The results demonstrate that minocycline reduces the number of activated microglial cells and oxidative stress, which rescue from Zn-induced changes in the expression of monoamine transporter and nigrostriatal dopaminergic neurodegeneration.
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?
Minocycline suppresses microglia activation.
“This effect is mainly ascribable to the minocycline-dependent suppression of microglia activation, which has been reported by several in vivo studies [251,258,259,260,261,262,263].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [263]
Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 315,771 · see citing works
Mechanisms underlying inflammation in neurodegeneration
Glass, C. K., Saijo, K., Winner, B., Marchetto, M. C., & Gage, F. H. (2010) · Cell · doi:10.1016/j.cell.2010.02.016 · Cited by 3,580 · see citing works
Wu, D. C., Jackson-Lewis, V., Vila, M., Tieu, K., Teismann, P., Vadseth, C., Choi, D.-K., Ischiropoulos, H., & Przedborski, S. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-05-01763.2002 · Cited by 1,183 · see citing works
Zhu, S., Stavrovskaya, I. G., Drozda, M., Kim, B. Y. S., Ona, V. O., Li, M., Sarang, S. S., Liu, A. S., Hartley, D. M., Wu, D. C., et al. (2002) · Nature · doi:10.1038/417074a · Cited by 1,071 · see citing works
DEXTER, D. T., CARAYON, A., JAVOY-AGID, F., AGID, Y., WELLS, F. R., DANIEL, S. E., LEES, A. J., JENNER, P., & MARSDEN, C. D. (1991) · Brain · doi:10.1093/brain/114.4.1953 · Cited by 1,043 · cited 1× · see citing works
“Increased accumulation of heavy metals, such as iron (Fe), zinc (Zn) and manganese (Mg) in the brain of PD patients emphasizes their possible role in PD [3].”
BackgroundDu, Y., Ma, Z., Lin, S., Dodel, R. C., Gao, F., Bales, K. R., Triarhou, L. C., Chernet, E., Perry, K. W., Nelson, D. L. G., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.251341998 · Cited by 789 · see citing works
Wu, D., Teismann, P., Tieu, K., Vila, M., Jackson-Lewis, V. R., Ischiropoulos, H., & Przedborski, S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0937239100 · Cited by 634 · see citing works
Dopamine transporters and neuronal injury
Miller, G. W., Gainetdinov, R. R., Levey, A. I., & Caron, M. G. (1999) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(99)01379-6 · Cited by 371 · see citing works
Critical Role for Microglial NADPH Oxidase in Rotenone-Induced Degeneration of Dopaminergic Neurons
Gao, H., Liu, B., & Hong, J. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-15-06181.2003 · Cited by 338 · see citing works
Induction and Activation by Zinc of NADPH Oxidase in Cultured Cortical Neurons and Astrocytes
Noh, K., & Koh, J. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-23-j0001.2000 · Cited by 335 · see citing works
Kraus, R. L., Pasieczny, R., Lariosa-Willingham, K. D., Turner, M. S., Jiang, A., & Trauger, J. W. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03219.x · Cited by 322 · see citing works
Oxidative and Inflammatory Pathways in Parkinson’s Disease
Miller, R. L., James-Kracke, M., Sun, G. Y., & Sun, A. Y. (2009) · Neurochemical Research · doi:10.1007/s11064-008-9656-2 · Cited by 306 · see citing works
Heme oxygenase-1 and neurodegeneration: expanding frontiers of engagement
Schipper, H. M., Song, W., Zukor, H., Hascalovici, J. R., & Zeligman, D. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06160.x · Cited by 298 · see citing works
Microglial activation as a priming event leading to paraquat-induced dopaminergic cell degeneration
Purisai, M. G., McCormack, A. L., Cumine, S., Li, J., Isla, M. Z., & Monte, D. A. D. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.10.008 · Cited by 255 · see citing works
Pathology of Parkinson's Disease
Jellinger, K. A. (2006) · doi:10.5040/9798216029700.0007 · Cited by 207 · see citing works
Singhal, N. K., Srivastava, G., Patel, D. K., Jain, S. K., & Singh, M. P. (2010) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2010.00819.x · Cited by 166 · see citing works
Self-citationCristóvão, A. C., Choi, D.-H., Baltazar, G., Beal, M. F., & Kim, Y.-S. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2459 · Cited by 165 · see citing works
The Role of Microglia in Paraquat-Induced Dopaminergic Neurotoxicity
Wu, X.-F., Block, M. L., Zhang, W., Qin, L., Wilson, B. C., Zhang, W.-Q., Veronesi, B., & Hong, J. (2005) · Antioxidants and Redox Signaling · doi:10.1089/ars.2005.7.654 · Cited by 158 · see citing works
Zhao, F., Cai, T., Liu, M., Zheng, G., Luo, W., & Chen, J. (2008) · Toxicological Sciences · doi:10.1093/toxsci/kfn213 · Cited by 157 · see citing works
Hung, S., Liou, H., Kang, K., Wu, R., Wen, C.-C., & Fu, W. (2008) · Molecular Pharmacology · doi:10.1124/mol.108.048611 · Cited by 133 · see citing works
Hong, H., Zeng, J.-S., Kreulen, D. L., Kaufman, D. I., & Chen, A. F. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01270.2005 · Cited by 131 · see citing works
Bartels, A. L., & Leenders, K. L. (2007) · Movement Disorders · doi:10.1002/mds.21552 · Cited by 127 · see citing works
Tanaka, S., Ishii, A., Ohtaki, H., Shioda, S., Yoshida, T., & Numazawa, S. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-143 · Cited by 118 · see citing works
Heo, K., Cho, Y., Cho, K., Kim, H., Kim, H., Shin, H. Y., Lee, B. I., & Kim, G. W. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.01.027 · Cited by 97 · see citing works
Zhang, W., Yan, Z., Gao, J., Sun, L., Huang, X., Liu, Z., Yu, S., Cao, C.-J., Zuo, L.-J., Chen, Z., et al. (2013) · Molecular Neurobiology · doi:10.1007/s12035-013-8586-4 · Cited by 90 · see citing works
Yokoyama, H., Kuroiwa, H., Yano, R., & Araki, T. (2008) · Neurological Sciences · doi:10.1007/s10072-008-0986-2 · Cited by 85 · see citing works
Zinc-induced apoptosis in substantia nigra of rat brain: neuroprotection by vitamin D3
Lin, A. M., Fan, S., Yang, D., Hsu, L. L., & Yang, J. C. (2003) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(03)00105-9 · Cited by 78 · see citing works
Agrawal, S., Singh, A. K., Tripathi, P., Mishra, M., Singh, P. K., & Singh, M. P. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-8696-7 · Cited by 76 · see citing works
Kumar, A., Singh, B. K., Ahmad, I., Shukla, S., Patel, D. K., Srivastava, G., Kumar, V., Pandey, H. P., & Singh, C. (2011) · Brain Research · doi:10.1016/j.brainres.2011.12.028 · Cited by 68 · see citing works
Self-citationZhang, P., Wong, T. A., Lokuta, K. M., Turner, D. E., Vujisic, K., & Liu, B. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.02.013 · Cited by 68 · see citing works
Kumar, A., Ahmad, I., Shukla, S., Singh, B. K., Patel, D. K., Pandey, H. P., & Singh, C. (2010) · Free Radical Research · doi:10.3109/10715762.2010.492832 · Cited by 65 · see citing works
Self-citationSrivastava, G., Dixit, A., Yadav, S., Patel, D. K., Prakash, O., & Singh, M. P. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.02.005 · Cited by 65 · see citing works
Self-citationDixit, A., Srivastava, G., Verma, D., Mishra, M., Singh, P. K., Prakash, O., & Singh, M. P. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.03.019 · Cited by 64 · see citing works
Minocycline attenuates iron neurotoxicity in cortical cell cultures
Chen‐Roetling, J., Chen, L., & Regan, R. F. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.06.026 · Cited by 62 · see citing works
Jourdain, S., Morissette, M., Morin, N., & Paolo, T. D. (2005) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2005.01337.x · Cited by 56 · see citing works
Singh, A. K., Tiwari, M. N., Dixit, A., Upadhyay, G., Patel, D. K., Singh, D., Prakash, O., & Singh, M. P. (2011) · Toxicological Sciences · doi:10.1093/toxsci/kfr115 · Cited by 56 · see citing works
Self-citationSingh, C., Ahmad, I., & Kumar, A. (2007) · PubMed · Cited by 54 · see citing works
Self-citationSingh, S., Singh, K., Patel, S., Patel, D. K., Singh, M. P., Nath, C., & Singh, M. P. (2008) · Brain Research · doi:10.1016/j.brainres.2008.02.023 · Cited by 42 · see citing works
Self-citationChien, W., Lee, T.-R., Hung, S., Kang, K., Lee, M., & Fu, W. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07229.x · Cited by 38 · see citing works
Singh, B. K., Kumar, A., Ahmad, I., Kumar, V., Patel, D. K., Jain, S. K., & Singh, C. (2011) · Free Radical Research · doi:10.3109/10715762.2011.607164 · Cited by 32 · see citing works
Self-citation
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
Wong, K. A., & Benowitz, L. I. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231710179 · Cited by 66 · see citing works
- Authors
- Kumar, V., Singh, B. K., Chauhan, A. K., Singh, D., Patel, D. K., & Singh, C.
- Affiliations
- Council of Scientific and Industrial Research (IN)
- Indian Institute of Toxicology Research (IN)
- Corresponding author
- Singh, Chetna
- Venue
- Molecular Neurobiology
- Published
- 2015-03-13
- Volume
- 53
- Issue
- 5
- Pages
- 2761-2777
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- OpenAlex
- W2137385714
- Cited by
- 37
- References
- 40
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 4 · 2022: 6 · 2021: 6 · 2020: 5 · 2019: 1 · 2018: 1 · 2017: 5 · 2016: 2 · 2015: 1
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Molecular Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- minocycline, zinc neurotoxicity, Parkinson's disease, microglial activation, oxidative stress, lipid peroxidation, NADPH oxidase, p67phox, cytochrome c release, caspase-3, tyrosine hydroxylase, dopamine transporter, vesicular monoamine transporter 2, heme oxygenase-1, substantia nigra, neurobehavioral impairment
- MeSH terms
- Animals, Behavior, Animal, Dopamine, Gene Expression Regulation, Male, Minocycline, Mitochondria, Motor Activity, Nerve Degeneration, Nerve Tissue Proteins, Substantia Nigra, Tyrosine 3-Monooxygenase, Zinc, Lipid Peroxidation, Rats, Wistar, Microglia, Oxidative Stress, NADPH Oxidases, Membrane Transport Proteins, Antigens, Nuclear, CD11b Antigen, Cytochromes c, Rotarod Performance Test, Heme Oxygenase-1, Caspase 3, Metabolome, Dopaminergic Neurons
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
