Manganese-Disrupted Interaction of Dopamine D1 and NMDAR in the Striatum to Injury Learning and Memory Ability of Mice

Overview

Journal Mol Neurobiol

Specialties Molecular Biology
Neurology

Date 2015 Dec 15

PMID 26660110

Citations 13

Authors

Qifan Song

Yu Deng

Xinxin Yang

Ying Bai

Bin Xu

Wei Liu

Wenxue Zheng

Can Wang

Meng Zhang

Zhaofa Xu

Affiliations

Soon will be listed here.

Abstract

Manganese (Mn) is widely regarded as a neurotoxic heavy metal that causes learning and memory deficits. Recently, it has been proved that the striatum is related to memory and learning ability. However, no previous study focused on the effect of Mn-induced learning and memory deficits on the striatum. This study aims to investigate the probable interaction of dopamine D1 receptor (DR1) and N-methyl-D-aspartate receptor (NMDAR), two cognition-related receptors in the striatum during Mn exposure. Mice are randomly divided into four groups, including control group, 12.5 mg/kg MnCl group, 25 mg/kg MnCl group, and 50 mg/kg MnCl group. The mice receive intraperitoneal injections of 0, 12.5, 25, and 50 mg/kg MnCl once daily for 2 weeks. Then, learning and memory ability, pathological changes, expression, and interaction of DR1 and NMDAR are determined. It has been found that Mn disrupted spatial learning and memory ability of mice by Morris water maze test and the passive avoidance test. Pathological and ultrastructure were injured. Mn decreased the immunohistochemical activities, protein levels, and messenger RNA (mRNA) expression of DR1, NR1, and NR2A. Mn exposure inhibited interaction between DR1 and NMDAR in striatum by double immunofluorescent staining and co-immunoprecipitation. In conclusion, our study illustrated that Mn caused learning and memory dysfunction via injury of striatum and inhibition of interaction between DR1 and NMDAR in striatum.

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