Okadaic acid induced Tau phosphorylation in rat brain: Role of NMDA receptor
IR@CDRI: CSIR-Central Drug Research Institute, Lucknow
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| Creator |
Kamat, P K
Rai, Shivika Swarnkar, Supriya Shukla, Rakesh Ali, Shakir Najmi, A K Nath, Chandishwar |
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| Date |
2013-10-07T10:18:02Z
2013-10-07T10:18:02Z 2013 |
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| Identifier |
Neuroscience, 2013, 238, 97–113
http://hdl.handle.net/123456789/1132 |
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| Description |
Okadaic acid (OKA) is potent inhibitor of protein phosphatases 1/2A (PP2A). Inhibition of PP2A leads to hyperphosphorylation of Tau protein. Hyperphosphorylated Tau protein is present in intraneuronal neurofibrillary tangles a characteristic feature of neuropathology of Alzheimer’s disease. Intracerebroventricular (ICV) administration of OKA causes neurotoxicity, which is associated with increased intracellular Ca2+ level, oxidative stress, and mitochondrial dysfunction in the brain areas. The present study explored Tau phosphorylation in OKA treated rats in relation to memory function, PP2A activity, intracellular Ca2+, GSK-3β and NMDA receptor After 13 days of OKA (200ng, ICV) administration in rats, memory was found impaired in water maze test. OKA induced memory-impaired rats showed increased mRNA and protein expression of Tau, CaMKII, Calpain and GSK3β in hippocampus and cerebral cortex. On the other hand, mRNA expression and activity of PP2A was reduced in these brain areas. OKA treatment also, resulted into decrease in mRNA expression of C and N terminal of Tau. Treatment with NMDA antagonist, MK801 (0.05mg/kg, i.p) for 13 days significantly prevented OKA induced changes in expression of PP2A, Tau, GSK3β, CaMKII and Calpain. Further, daily administration of anticholinergic drug, Donepezil (5mg/kg, p.o), and NMDA receptor antagonist, Memantine (10mg/kg, p.o) initiated after OKA administration for 13 days significantly attenuated OKA induced variation in Tau, Tau-C terminal, Tau-N terminal CaMKII, Calpain, PP2A and GSK3β. These results infer that NMDA antagonist MK801 and memantine are effective against OKA induced neurotoxicity. Therefore, present study clearly indicates the involvement of NMDA receptor in OKA (ICV) induced Tau hyperphosphorylation.
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606879 bytes
application/pdf |
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| Language |
en
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| Relation |
CDRI Communication No. 8399
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| Subject |
Okadaic acid
Alzheimer’s disease Tau NMDA Donepezil Memantine |
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| Title |
Okadaic acid induced Tau phosphorylation in rat brain: Role of NMDA receptor
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Article
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