Antagonistic effect of nimodipine on DBP-induced learning and memory impairment in KM mice / 中国药理学通报

ABSTRACT

Aim To explore the antagonistic effect of nimodipine (Nim) on dibutyl phthalate (DBP)-in-duced learning and memory impairment in KM mice. Methods Thirty-six male KM mice were treated with saline (control), 50 mg • kg-1 DBP, 2 mg • kg-1 Nim, and DBP + Nim lasted for 28 days. The latency of KM mice in each group was measured. Levels of calmodulin (CaM), calmodulin/calmodulin-dependent protein kinase II ( CaMKII ) , protein kinase C (PKC) , cytochrome C (Cyt C) and caspase-3 in hippocampus of KM mice in each group were detected. And expressions of ERK1/2 and p-ERKl/2 were evaluated. In addition, the pathological changes of hipp-ocampal CAI region were also analyzed by HE, Nissl staining, and TUNEL assay. Results Compared with 50 mg • kg-1 DBP group, the learning and memory im-pairment of KM mice in DBP + Nim group was alleviated, the pathological damage and apoptosis in CA1 region of hippocampus were reduced, the levels of PKC, Cyt C, caspase-3 and p-ERKl/2 decreased, while the levels of CaM and CaMKII increased accordingly (P < 0.05). Conclusions DBP affects Ca2 +-related proteins and up-regulates p-ERKl/2 expression, inducing hippocampal neuronal damage and apoptosis, whereas Nim can improve DBP-induced learning and memory impairment in KM mice, which may be related to the ability of Nim to reduce the levels of p-ERKl/2 and caspase-3 in brain tissues of mice after DBP exposure by blocking DBP-induced Ca2+ concentration.