title: Inhibition of central angiotensin converting enzyme ameliorates scopolamine induced memory impairment in mice: role of cholinergic neurotransmission, cerebral blood flow and brain energy metabolism.
abstract: Evidences indicate that inhibition of central Renin angiotensin system (RAS) ameliorates memory impairment in animals and humans. Earlier we have reported involvement of central angiotensin converting enzyme (ACE) in streptozotocin induced neurodegeneration and memory impairment. The present study investigated the role of central ACE in cholinergic neurotransmission, brain energy metabolism and cerebral blood flow (CBF) in model of memory impairment induced by injection of scopolamine in mice. Perindopril (0.05 and 0.1 mg/kg, PO) was given orally for one week before administration of scopolamine (3mg/kg, IP). Then, memory function was evaluated by Morris water maze and passive avoidance tests. CBF was measured by laser Doppler flowmetry. Biochemical and molecular parameters were estimated after the completion of behavioral studies. Scopolamine caused impairment in memory which was associated with reduced CBF, acetylcholine (ACh) level and elevated acetylcholinesterase (AChE) activity and malondialdehyde (MDA) level. Perindopril ameliorated scopolamine induced amnesia in both the behavioral paradigms. Further, perindopril prevented elevation of AChE and MDA level in mice brain. There was a significant increase in CBF and ACh level in perindopril treated mice. However, scopolamine had no significant effect on ATP level and mRNA expression of angiotensin receptors and ACE in cortex and hippocampus. But, perindopril significantly decreased ACE activity in brain without affecting its mRNA expression. The study clearly showed the interaction between ACE and cholinergic neurotransmission and beneficial effect of perindopril can be attributed to improvement in central cholinergic neurotransmission and CBF.
authors.affiliation: Division of Pharmacology, Central Drug Research Institute, Lucknow (UP), India.
authors.forename: Santoshkumar
authors.initials: S
authors.lastname: Tota
authors.forename: Chandishwar
authors.initials: C
authors.lastname: Nath
authors.forename: Abul Kalam
authors.initials: AK
authors.lastname: Najmi
authors.forename: Rakesh
authors.initials: R
authors.lastname: Shukla
authors.forename: Kashif
authors.initials: K
authors.lastname: Hanif
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000517:prevention & control* / Q000523:psychology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis / Q000502:physiology*; D020913:Perindopril / Q000008:administration & dosage / Q000494:pharmacology; D012601:Scopolamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D018727:Muscarinic Antagonists; D000255:Adenosine Triphosphate; D012601:Scopolamine; D000110:Acetylcholinesterase; D007703:Peptidyl-Dipeptidase A; D020913:Perindopril