Okadaic acid induced neurotoxicity leads to central cholinergic dysfunction in rats

Pradeep Kumar Kamat, Santoshkumar Tota, Shivika Rai, Rakesh Shukla, Shakir Ali, Abul Kalam Najmi, Chandishwar Nath

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Central cholinergic system is involved in regulation of memory and disturbances in these results in memory loss. Previously, we examined the effect of okadaic acid, OKA (200 ng, i.c.v.) on memory impairment and mitochondrial dysfunction in rats. In the present study, we investigated effect of OKA (i.c.v) on cholinergic function by observing acetylcholine level (ACh), acetylcholinestrase (AChE) activity, and mRNA expression of acetylcholinestrase and α7nicotinic receptor (α7-nAChR) as a cholinergic markers in brain areas (cerebellum, striatum cortex and hippocampus). In present work OKA, caused a significant decrease in acetylcholine level, acetylcholinestrase activity and mRNA expression of acetylcholinestrase and α7-nicotinic receptor in rat but these changes were mainly observed in cortex and hippocampus. Further, histopathological study by cresyl violet staining showed neuronal loss in cortex and hippocampus after OKA administration indicating neurotoxicity. Pretreatment with anti-dementic drugs donepezil (AChE inhibitor; 5 mg/kg, p.o) and memantine (NMDA receptor antagonist; 10 mg/kg, p.o) daily for 13 day prevented cholinergic dysfunction and neuronal loss in cortex and hippocampus of OKA treated rat. Daily per se treatment for 13 day with donepezil decreased acetylcholinestrase activity and increased mRNA expression of acetylcholinestrase and α7-nicotinic receptor. Whereas, per se treatment with memantine daily for 13 day did not affect acetylcholinestrase activity, mRNA expression of acetylcholinestrase and α7-nicotinic receptor. Findings of this work shows that OKA (i.c.v.), apart from memory impairment and mitochondrial dysfunction, as our previous study showed, also induced cholinergic dysfunction and neuronal loss, which can be addressed by antidementic drugs like donepezil and memantine.

Original languageEnglish (US)
Pages (from-to)90-98
Number of pages9
JournalEuropean Journal of Pharmacology
Volume690
Issue number1-3
DOIs
StatePublished - Sep 5 2012
Externally publishedYes

Keywords

  • Cholinergic dysfunction
  • Memory
  • Okadaic acid
  • α7-nicotinic acetylcholine receptor

ASJC Scopus subject areas

  • Pharmacology

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