NDLI: Role of Secondary Mediators in Caffeine-Mediated Neuroprotection in Maneb- and Paraquat-Induced Parkinson’s Disease Phenotype in the Mouse

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Role of Secondary Mediators in Caffeine-Mediated Neuroprotection in Maneb- and Paraquat-Induced Parkinson’s Disease Phenotype in the Mouse

Content Provider	Springer Nature Link
Author	Yadav, Sharawan Gupta, Satya Prakash Srivastava, Garima Srivastava, Pramod Kumar Singh, Mahendra Pratap
Copyright Year	2011
Abstract	Maneb and paraquat are known to induce Parkinson’s disease (PD) phenotype, however, caffeine offers neuroprotection. Nitric oxide (NO) acts an important mediator in PD phenotype and tyrosine kinase (TK), nuclear factor kappa B (NF-kB), p38 mitogen activated protein kinase (p38 MAPK) are known to regulate its production. The present study aimed to elucidate the role of caffeine in the regulation of NO production and microglial activation and their subsequent contribution in dopaminergic neuroprotection. The animals were treated with caffeine and/or maneb and paraquat along with controls. In a few sets of experiments, the animals were also treated with aminoguanidine, an inhibitor of inducible NO synthase, pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-kB, genistein, an inhibitor of TK or SB202190, an inhibitor of p38 MAPK. Tyrosine hydroxylase (TH)-immunoreactivity and anti-integrin αM (OX-42) staining were performed to assess the number of dopaminergic neurons and activation of microglia, respectively. NO was measured in terms of nitrite, however, the expressions of p38 MAPK, interleukin (IL)-1β, NF-kB and TK were checked by western blot analyses. Maneb and paraquat induced the number of degenerating dopaminergic neurons, microglial cells, nitrite content, expressions of IL-1β, p38 MAPK, NF-kB and TK and caffeine co-treatment reduced the level of such alterations. Reductions were more pronounced in the animals co-treated with aminoguanidine, PDTC, genistein or SB202190. The results obtained thus demonstrate that caffeine down-regulates NO production, neuroinflammation and microglial activation, which possibly contribute to neuroprotection.
Starting Page	875
Ending Page	884
Page Count	10
File Format	PDF
ISSN	03643190
Journal	Neurochemical Research
Volume Number	37
Issue Number	4
e-ISSN	15736903
Language	English
Publisher	Springer US
Publisher Date	2011-12-27
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Parkinson’s disease Maneb Paraquat Caffeine Nitric oxide Neuroprotection Neurochemistry Neurology Cell Biology Biochemistry Neurosciences
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Cellular and Molecular Neuroscience

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