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Sci. Pharm. 2012, 80(3), 647-662; doi:10.3797/scipharm.1203-06

Chronic Inhibition of Central Angiotensin-Converting Enzyme Ameliorates Colchicine-Induced Memory Impairment in Mice

1
Amity University, Uttar Pradesh, India
2
Faculty of Pharmacy, Integral University, Lucknow, India
*
Author to whom correspondence should be addressed.
Received: 22 March 2012 / Accepted: 3 May 2012 / Published: 3 May 2012
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Abstract

Preclinical and clinical studies indicated involvement of the central renin-angiotensin system (RAS) in memory functions. However, the role of central angiotensin-converting enzyme (ACE) in memory function is still unclear. The present study investigated the involvement of central ACE in colchicine-induced memory impairment in the context of cholinergic function and oxidative stress. Memory impairment was induced by intracerebral colchicine administration in mice. The ACE inhibitor, perindopril (0.05 and 0.1 mg/kg/day), was administered orally for 14 days. Memory function was evaluated by the Morris water maze (MWM) test from the 14th day on after colchicine injection. Donepezil was used as a standard. Parameters of oxidative stress and cholinergic function, ACE activity in serum and the brain were estimated after the completion of behavioral studies. Colchicine caused memory impairment as revealed by no significant change in latency to reach a hidden platform in the MWM test. Furthermore, there was a significant increase in MDA, ROS, and nitrite levels with a reduction in GSH level and acetylcholinesterase (AChE) activity in the brain of colchicine-treated mice. Colchicine significantly increased brain ACE activity without affecting serum ACE. Donepezil prevented colchicine-induced memory impairment in mice. The antidementic effect of perindopril may be attributed to reduced oxidative stress and improvement in cholinergic function. Moreover, the elevated brain ACE activity was also inhibited by perindopril. The study showed that central ACE plays an important role in colchicine-induced memory deficit, corroborating a number of studies that show that treatment with ACE inhibitors could be neuroprotective.
Keywords: Perindopril; Renin angiotensin system; Acetylcholinesterase; Oxidative stress Perindopril; Renin angiotensin system; Acetylcholinesterase; Oxidative stress
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

AWASTHI, H.; KAUSHAL, D.; SIDDIQUI, H.H. Chronic Inhibition of Central Angiotensin-Converting Enzyme Ameliorates Colchicine-Induced Memory Impairment in Mice. Sci. Pharm. 2012, 80, 647-662.

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