Research article summary (published 15 Jun 2008):

Involvement of angiotensin converting enzyme in cerebral hypoperfusion induced anterograde memory impairment and cholinergic dysfunction in rats.

Full Abstract

Forebrain cholinergic dysfunction is the hallmark of vascular dementia (VaD) and Alzheimer's dementia (AD) induced by cerebral hypoperfusion during aging. The aim of the present study is to evaluate the role of angiotensin converting enzyme (ACE) in cerebral hypoperfusion-induced dementia and cholinergic dysfunction. Chronic cerebral hypoperfusion (CHP) was induced by permanent bilateral common carotid artery (2VO) occlusion in rats. Chronic cerebral hypoperfusion resulted in anterograde memory impairment revealed from Morris water maze (MWM) and passive avoidance step through tasks (PA), which was significantly attenuated by ACE inhibitor, captopril. Cerebral hypoperfusion down-regulated the relative expression of cholinergic muscarinic receptor (ChM-1r) and choline acetyltransferase (ChAT) as well as up-regulated the angiotensin II type-1 receptor (AT-1) expression in hippocampus of vehicle treated CHP group on the 54th day post-hypoperfusion. The diminished number of presynaptic cholinergic neurons and the pyramidal neurons were evident from ChAT-immunofluorescence and the hematoxylin and eosin (H&E) staining studies respectively in hippocampal Cornu ammonis1 (CA1); region of vehicle-treated hypoperfused animals. Further the lipid peroxidation level was also found to be elevated in the hippocampus of the vehicle-treated group. Our results demonstrated that continuous captopril treatment (50 mg/kg, i.p. twice daily) for 15 days mitigated the hypoperfusion-induced cholinergic hypofunction and neurodegeneration in hippocampus. The present study robustly reveals that the angiotensinergic system plays a pivotal role in progression of neuronal death and memory dysfunctions during cerebral hypoperfusion.

Author information

Author/s: Kumaran, D (D); Udayabanu, M (M); Kumar, M (M); Aneja, R (R); Katyal, A (A);

Affiliation: Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi 110007, India. mdram2002(-atsign-)yahoo.co.in

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Neuroscience (Neuroscience), published in United States. (Language: eng)

Reference: 2008-Aug; vol 155 (issue 3) : pp 626-39

Dates: Created 2008/08/20; Completed 2008/12/18;

PMID: 18621107, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Acetylcholine - metabolism Amnesia, Anterograde - etiology; metabolism; pathology Analysis of Variance Animals Avoidance Learning - drug effects; physiology Behavior, Animal Captopril - pharmacology Cholinesterases - metabolism Disease Models, Animal Enzyme Inhibitors - pharmacology Gene Expression Regulation - drug effects; physiology

Hippocampus - drug effects; metabolism Infarction, Middle Cerebral Artery - complications Lipid Peroxidation - drug effects; physiology Male Malondialdehyde - metabolism Maze Learning - drug effects; physiology Peptidyl-Dipeptidase A - genetics; metabolism Rats Rats, Sprague-Dawley Reaction Time - drug effects; physiology Time Factors

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Enzyme Inhibitors (0) ; Acetylcholine (51-84-3) ; Malondialdehyde (542-78-9) ; Captopril (62571-86-2) ; Cholinesterases (EC 3.1.1.8) ; Peptidyl-Dipeptidase A (EC 3.4.15.1)

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