PDF(Pubmed)
Abstract：
Astrocytic receptors influence cognitive function and can promote behavioral deficits in disease. These effects may vary based on variables such as biological sex, but it is not known if the effects of astrocytic receptors are dependent on sex. We leveraged in vivo gene editing and chemogenetics to examine the roles of astrocytic receptors in spatial memory and other processes. We show that reductions in metabotropic glutamate receptor 3 (mGluR3), the main astrocytic glutamate receptor in adults, impair memory in females but enhance memory in males. Similarly, increases in astrocytic mGluR3 levels have sex-dependent effects and enhance memory in females. mGluR3 manipulations also alter spatial search strategies during recall in a sex-specific manner. In addition, acute chemogenetic stimulation of Gi/o-coupled or Gs-coupled receptors in hippocampal astrocytes induces bidirectional and sex-dimorphic effects on memory. Thus, astrocytes are sex-dependent modulators of cognitive function and may promote sex differences in aging and disease.
摘要：
星形胶质细胞受体影响认知功能并可促进疾病中的行为缺陷。这些影响可能会根据生物性别等变量而有所不同，但目前尚不清楚星形细胞受体的作用是否依赖于性别。我们利用体内基因编辑和化学遗传学来研究星形细胞受体在空间记忆和其他过程中的作用。我们显示代谢型谷氨酸受体3（mGluR3）的减少，成人主要的星形胶质细胞谷氨酸受体，削弱女性的记忆力，但增强男性的记忆力。同样，星形胶质细胞mGluR3水平的增加具有性别依赖性作用，并增强女性的记忆力。mGluR3操作也以性别特异性方式改变回忆期间的空间搜索策略。此外,海马星形胶质细胞中Gi/o偶联或Gs偶联受体的急性化学遗传学刺激可诱导对记忆的双向和性别二态效应。因此，星形胶质细胞是认知功能的性别依赖性调节剂,可能促进衰老和疾病的性别差异.
