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Okadaic acid induced neurotoxicity leads to central cholinergic dysfunction in rats.
Eur J Pharmacol. 2012 Sep 05; 690(1-3):90-8.EJ

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 (200ng, 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; 5mg/kg, p.o) and memantine (NMDA receptor antagonist; 10mg/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.

Authors+Show Affiliations

Division of Pharmacology, CSIR-Central Drug Research Institute, PO Box 173, Lucknow (UP) 226001, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22749976

Citation

Kamat, Pradeep Kumar, et al. "Okadaic Acid Induced Neurotoxicity Leads to Central Cholinergic Dysfunction in Rats." European Journal of Pharmacology, vol. 690, no. 1-3, 2012, pp. 90-8.
Kamat PK, Tota S, Rai S, et al. Okadaic acid induced neurotoxicity leads to central cholinergic dysfunction in rats. Eur J Pharmacol. 2012;690(1-3):90-8.
Kamat, P. K., Tota, S., Rai, S., Shukla, R., Ali, S., Najmi, A. K., & Nath, C. (2012). Okadaic acid induced neurotoxicity leads to central cholinergic dysfunction in rats. European Journal of Pharmacology, 690(1-3), 90-8. https://doi.org/10.1016/j.ejphar.2012.06.006
Kamat PK, et al. Okadaic Acid Induced Neurotoxicity Leads to Central Cholinergic Dysfunction in Rats. Eur J Pharmacol. 2012 Sep 5;690(1-3):90-8. PubMed PMID: 22749976.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Okadaic acid induced neurotoxicity leads to central cholinergic dysfunction in rats. AU - Kamat,Pradeep Kumar, AU - Tota,Santoshkumar, AU - Rai,Shivika, AU - Shukla,Rakesh, AU - Ali,Shakir, AU - Najmi,Abul Kalam, AU - Nath,Chandishwar, Y1 - 2012/06/29/ PY - 2012/03/13/received PY - 2012/05/29/revised PY - 2012/06/08/accepted PY - 2012/7/4/entrez PY - 2012/7/4/pubmed PY - 2012/12/18/medline SP - 90 EP - 8 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 690 IS - 1-3 N2 - 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 (200ng, 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; 5mg/kg, p.o) and memantine (NMDA receptor antagonist; 10mg/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. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/22749976/Okadaic_acid_induced_neurotoxicity_leads_to_central_cholinergic_dysfunction_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(12)00518-3 DB - PRIME DP - Unbound Medicine ER -