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The objective of the present study was to examine the beneficial effect of the calcium channel blocker, nimodipine, on diabetes\u2010induced cognitive deficits and altered calcium homeostasis in the cerebral cortex. Diabetes was induced in mice by intraperitoneal injection of streptozotocin (40 mg\/kg body wt) for 5 days. Nimodipine (10 mg\/kg body weight) was administered intraperitoneally to the animals every 48 hr for 8 weeks. A significant impairment in spatial learning and memory was observed in diabetic animals, which was reversed by nimodipine treatment. Diabetic animals showed increased CaV1.2 mRNA and protein expression, which might be responsible for enhanced synaptosomal calcium uptake. Nimodipine treatment was found to lower CaV1.2 mRNA, protein expression, and calcium uptake. Mitochondrial Ca<jats:sup>2+<\/jats:sup> uptake was reduced in diabetic brains, which was reversed with nimodipine treatment. Plasma membrane and sarcoplasmic reticulum Ca<jats:sup>2+<\/jats:sup>\u2010ATPase activity was found to be significantly decreased in diabetic animals, whereas nimodipine supplementation restored the activity of both Ca<jats:sup>2+<\/jats:sup>\u2010ATPases nearly to control values. Nimodipine treatment was shown to normalize intracellular free Ca<jats:sup>2+<\/jats:sup> levels in diabetic animals. Nimodipine was shown to attenuate increased calpain activity measured in terms of hydrolysis of fluorogenic substrate and \u03b1II\u2010spectrin degradation. Nimodipine supplementation also reduced reactive oxygen species production and lipid peroxidation in diabetic animals. The data suggests that L\u2010type calcium channel blocker is beneficial in preventing cognitive deficits associated with diabetic encephalopathy through modulation of dysregulated calcium homeostasis. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jnr.23478","type":"journal-article","created":{"date-parts":[[2014,9,30]],"date-time":"2014-09-30T04:45:56Z","timestamp":1412052356000},"page":"296-308","source":"Crossref","is-referenced-by-count":12,"title":["L\u2010type calcium channel blocker ameliorates diabetic encephalopathy by modulating dysregulated calcium homeostasis"],"prefix":"10.1002","volume":"93","author":[{"given":"Kirti","family":"Singhal","sequence":"first","affiliation":[{"name":"Department of Biochemistry Panjab University Chandigarh India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajat","family":"Sandhir","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Panjab University Chandigarh 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