兴奋剂
多巴胺
神经科学
海马体
多巴胺能
内科学
内分泌学
链脲佐菌素
莫里斯水上航行任务
神经递质
认知功能衰退
线粒体生物发生
医学
心理学
线粒体
生物
受体
中枢神经系统
疾病
糖尿病
细胞生物学
痴呆
作者
Ling He,Yuhui Hu,Qing-Peng Xia,Chen Wang,Ling He
标识
DOI:10.1016/j.brainresbull.2021.07.015
摘要
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder characterized by irreversible cognitive deficits and memory dysfunction. Dopamine is the most abundant catecholaminergic neurotransmitter in the brain which regulates motivation, reward, movement, and cognition. Recently, increasing evidences have shown that dopaminergic system is disturbed in AD conditions, and pharmacological interventions targeting dopamine D1 receptor (DRD1) exhibit certain therapeutic benefits in AD models. However, the underlying link between DRD1 and AD remains elusive. This study sought to test whether the selective DRD1 agonist A-68930 could improve streptozotocin (STZ)-induced cognitive impairment in mice. Here we found that A-68930 treatment through intraperitoneal injection efficiently alleviated STZ-induced cognitive deficits in mice. Moreover, our mechanism researches revealed that the DRD1 signaling induced by A-68930 significantly rescued STZ-induced mitochondrial biogenesis deficit, mitochondrial dysfunction, Aβ overexpression, and tau phosphorylation in mice hippocampus and cortex and SH-SY5Y cells, which may be mediated through stimulating AMPK/PGC-1α pathway. This study indicates that DRD1 agonist A-68930 can improve STZ-induced cognitive deficits and mitochondrial dysfunction in vivo and in vitro, and DRD1 may represent an appropriate target candidate for AD drug development.
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