title: L-type calcium channel blockade alleviates molecular and reversal spatial learning and memory alterations induced by entorhinal amyloid pathology in rats.
abstract: The entorhinal cortex (EC) is one of the most vulnerable brain regions that is affected by beta amyloid (Aβ) in the early phases of Alzheimer's disease (AD). Calcium dyshomeostasis is one reason of Aβ pathology and the role of calcium channel blockers (CCBs) in this phenomenon has not fully understood. In this study, we investigated the possible neuroprotective effect of CCBs, nimodipine and isradipine against amyloid pathogenesis in EC. The Aβ 1-42 was injected bilaterally into the EC of male rats and spatial performance was assessed between 7 and 12 days after Aβ injection by Morris water maze test. Animals were daily treated by injection of various doses of nimodipine or isradipine (both at 3, 10, or 30 μg/2 μl) or their vehicles into the lateral ventricle until the start of behavioral test. Lesion in EC was assessed by measuring some proteinases involved in calcium dependent apoptotic pathway (calpain 2, caspase 12 and 3). Despite normal performance in probe test, Aβ treated rats showed delayed acquisition in a spatial reference memory task. Aβ treated rats revealed delayed acquisition in reversal memory and had deficit in probe test. The observed impairments were attenuated by isradipine (10 and 30 μg but not 3 μg) and nimodipine (30 μg). Calpain 2, caspase 12 and 3 were increased in the Aβ treated animals which was partially antagonized by isradipine and nimodipine. It is concluded that CCBs might have beneficial therapeutic effects in AD especially in the early phases of this disease.
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran 19839, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Gholamipour-Badie
authors.forename: Nima
authors.initials: N
authors.lastname: Naderi
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Shaerzadeh
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Motamedi
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002154:Calpain / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020287:In Situ Nick-End Labeling; D017275:Isradipine / Q000627:therapeutic use; D007859:Learning Disabilities / Q000139:chemically induced* / Q000188:drug therapy*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D009553:Nimodipine / Q000627:therapeutic use; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012193:Reversal Learning / Q000187:drug effects; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D002121:Calcium Channel Blockers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D009553:Nimodipine; D002154:Calpain; D020169:Caspases; D017275:Isradipine