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腹侧被盖区多巴胺神经元连接组和转译组的性一致性。

Sexual congruency in the connectome and translatome of VTA dopamine neurons.

机构信息

Department of Pharmacology, University of Washington, Seattle, WA, 98195, USA.

Department of Anatomy and Neurobiology, University of California, Irvine, CA, 92697, USA.

出版信息

Sci Rep. 2017 Sep 11;7(1):11120. doi: 10.1038/s41598-017-11478-5.

DOI:10.1038/s41598-017-11478-5
PMID:28894175
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5593921/
Abstract

The ventral tegmental area (VTA) dopamine system is important for reward, motivation, emotion, learning, and memory. Dysfunctions in the dopamine system are linked to multiple neurological and neuropsychiatric disorders, many of which present with sex differences. Little is known about the extent of heterogeneity in the basic organization of VTA dopamine neurons with regard to sex. Here, we characterized the cell-specific connectivity of VTA dopamine neurons, their mRNA translational profile, and basic electrophysiological characteristics in a common strain of mice. We found no major differences in these metrics, except for differential expression of a Y-chromosome associated mRNA transcript, Eif2s3y, and the X-linked, X-inactivation transcript Xist. Of note, Xist transcript was significantly enriched in dopamine neurons, suggesting tight regulation of X-linked gene expression to ensure sexual congruency. These data indicate that the features that make dopamine neurons unique are highly concordant and not a principal source of sexual dimorphism.

摘要

腹侧被盖区(VTA)多巴胺系统对奖励、动机、情感、学习和记忆很重要。多巴胺系统的功能障碍与多种神经和神经精神疾病有关,其中许多疾病表现出性别差异。关于 VTA 多巴胺神经元的基本组织在性别方面的异质性程度,人们知之甚少。在这里,我们描述了常见品系小鼠 VTA 多巴胺神经元的细胞特异性连接、它们的 mRNA 翻译谱和基本电生理特征。我们发现这些指标没有重大差异,除了 Y 染色体相关 mRNA 转录本 Eif2s3y 和 X 连锁、X 失活转录本 Xist 的差异表达。值得注意的是,Xist 转录本在多巴胺神经元中明显富集,这表明 X 连锁基因表达受到严格调控,以确保性别一致性。这些数据表明,使多巴胺神经元具有独特性的特征高度一致,不是性别二态性的主要来源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c636/5593921/b352a4c842c7/41598_2017_11478_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c636/5593921/a18fe52c630a/41598_2017_11478_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c636/5593921/76755df86d5e/41598_2017_11478_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c636/5593921/e835de9424a8/41598_2017_11478_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c636/5593921/30f4ccb6730a/41598_2017_11478_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c636/5593921/764e0c58d692/41598_2017_11478_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c636/5593921/b352a4c842c7/41598_2017_11478_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c636/5593921/a18fe52c630a/41598_2017_11478_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c636/5593921/76755df86d5e/41598_2017_11478_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c636/5593921/e835de9424a8/41598_2017_11478_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c636/5593921/30f4ccb6730a/41598_2017_11478_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c636/5593921/764e0c58d692/41598_2017_11478_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c636/5593921/b352a4c842c7/41598_2017_11478_Fig6_HTML.jpg

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