title: Central angiotensin converting enzyme facilitates memory impairment in intracerebroventricular streptozotocin treated rats.
abstract: Preclinical and clinical studies indicated involvement of renin angiotensin system (RAS) in memory functions. However, exact role of RAS in cognition is still ambiguous. Our aim was to explore how angiotensin converting enzyme (ACE) modulates memory in experimental model of memory impairment. Memory deficit was induced by intracerebroventricular administration of streptozotocin (STZ, 3mg/kg) in rats. Perindopril, an ACE inhibitor, was given for 21 days and memory function was evaluated by Morris water maze test. Cerebral blood flow (CBF) was measured by laser doppler flowmetry. The biochemical and expression studies were done in cortex and hippocampus of rat brain after the completion of behavioral studies. STZ caused impairment in memory along with significant reduction in CBF, ATP level and elevated oxidative and nitrosative stress. The activity and mRNA expression of acetylcholinesterase (AChE) and ACE were also increased in rat brain regions following STZ administration. However, serum ACE activity remained unaffected. Treatment with perindopril dose dependently improved memory by increasing energy metabolism and CBF. Perindopril also decreased oxidative and nitrosative stress, activity and mRNA expression of AChE and ACE in STZ treated rat. Further, ACE inhibition mitigated STZ induced neurodegeneration as observed in histopathological studies. Moreover, perindopril per se improved memory and CBF, decreased oxidative stress with no effect on AChE activity and expression. However, perindopril per se significantly reduced ACE activity but increased mRNA expression of ACE in rat brain. These results suggest that ACE occupies a pivotal role in STZ induced memory deficit thus implicating central RAS in cognition.
authors.affiliation: Division of Pharmacology, Central Drug Research Institute, Lucknow U.P.India.
authors.forename: Santoshkumar
authors.initials: S
authors.lastname: Tota
authors.forename: Pradeep Kumar
authors.initials: PK
authors.lastname: Kamat
authors.forename: Gunjan
authors.initials: G
authors.lastname: Saxena
authors.forename: Kashif
authors.initials: K
authors.lastname: Hanif
authors.forename: Abul Kalam
authors.initials: AK
authors.lastname: Najmi
authors.forename: Chandishwar
authors.initials: C
authors.lastname: Nath
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000201:enzymology* / Q000523:psychology; D009043:Motor Activity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D020913:Perindopril / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000008:administration & dosage
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D013311:Streptozocin; D000110:Acetylcholinesterase; D007703:Peptidyl-Dipeptidase A; D005978:Glutathione; D020913:Perindopril