Nimodipine's protection against corticosterone-induced morphological changes in the hippocampus of young rats

Abstract

Sustained high levels of corticosterone (CORT), one of the major stress-induced hormones in the rat, were suggested as generating `accelerated brain aging' and were shown to induce both specific brain changes in the hippocampus and learning impairments in young and middle-aged Fischer-344 rats. Evidence that altered calcium (Ca) homeostasis may play a major role in brain aging has accumulated over the last decade. Recently, new data established a connection between glucocorticoids and voltage-activated Ca influx in aged hippocampal neurons. In the present study, an attempt was made to block the CORT-induced `accelerated aging' by the simultaneous administration of the L-type Ca channel blocker nimodipine. CORT or placebo sustained-release (SR) pellets were implanted subcutaneously in 3 months old Fischer male rats. Each group was further sub-divided between nimodipine and placebo SR treatments. Characteristic CORT-induced morphological changes were observed in pyramidal hippocampal cells, such as at the CA1 and CA4 sub-regions (22.2%±7.7 and 28.6%±8.4 of pyknotic cells without clear nuclei, respectively). Concomitant treatment with nimodipine conferred full protection against CORT-induced morphological changes (e.g. 3.2%±0.8 and 2.1%±1.9 of pyknotic cells in CA1 and CA4, n=7 rats in each group; P<0.04). The neuroprotective efficacy of nimodipine supports the theory of Ca involvement in CORT related `accelerated brain aging'.