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性别和自闭症谱系障碍对人类黑质致密部多巴胺能神经元中催产素受体结合和 mRNA 表达的影响。

Effect of sex and autism spectrum disorder on oxytocin receptor binding and mRNA expression in the dopaminergic pars compacta of the human substantia nigra.

机构信息

Department of Biology, Utah State University, Logan, UT 84322, USA.

California National Primate Research Center, University of California Davis, Davis, CA 95616, USA.

出版信息

Philos Trans R Soc Lond B Biol Sci. 2022 Aug 29;377(1858):20210118. doi: 10.1098/rstb.2021.0118. Epub 2022 Jul 11.

Abstract

Oxytocin is an endogenous neuropeptide hormone that influences social behaviour and bonding in mammals. Variations in oxytocin receptor (OXTR) expression may play a role in the social deficits seen in autism spectrum disorder. Previous studies from our laboratory found a dense population of OXTR in the human substantia nigra (SN), a basal ganglia structure in the midbrain that is important in both movement and reward pathways. Here, we explore whether differences in OXTR can be identified in the dopaminergic SN pars compacta of individuals with autism. Postmortem human brain tissue specimens were processed for OXTR autoradiography from four groups: males with autism, females with autism, typically developing (TD) males and TD females. We found that females with autism had significantly lower levels of OXTR than the other groups. To examine potential gene expression differences, we performed hybridization in adjacent slides to visualize and quantify OXTR mRNA as well as mRNA for tyrosine hydroxylase. We found no differences in mRNA levels for either gene across the four groups. These results suggest that a dysregulation in local OXTR protein translation or increased OXTR internalization/recycling may contribute to the differences in social symptoms seen in females with autism. This article is part of the theme issue 'Interplays between oxytocin and other neuromodulators in shaping complex social behaviours'.

摘要

催产素是一种内源性神经肽激素,影响哺乳动物的社会行为和联系。催产素受体 (OXTR) 表达的变异可能在自闭症谱系障碍中所见的社会缺陷中发挥作用。我们实验室的先前研究发现,人类黑质 (SN) 中有大量的 OXTR,SN 是中脑的基底神经节结构,在运动和奖励途径中都很重要。在这里,我们探讨是否可以在自闭症患者的多巴胺能 SN 致密部中识别出 OXTR 的差异。我们从四个组的尸检人脑组织标本中进行了 OXTR 放射自显影处理:自闭症男性、自闭症女性、典型发育 (TD) 男性和 TD 女性。我们发现自闭症女性的 OXTR 水平明显低于其他组。为了检查潜在的基因表达差异,我们在相邻的幻灯片上进行了杂交,以可视化和量化 OXTR mRNA 以及酪氨酸羟化酶 mRNA。我们发现这两个基因在四个组中的 mRNA 水平均无差异。这些结果表明,局部 OXTR 蛋白翻译的失调或 OXTR 内化/回收的增加可能导致自闭症女性所见社会症状的差异。本文是主题为“催产素和其他神经调质在塑造复杂社会行为中的相互作用”的特刊的一部分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a57d/9272142/524e4925de8f/rstb20210118f03.jpg

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