雌雄 Fmr1 KO 小鼠的行为、神经递质和转录组分析

IF 2.6 3区 医学 Q2 BEHAVIORAL SCIENCES
Deirdre M. McCarthy, Cynthia Vied, Mia X. Trupiano, Angeli J. Canekeratne, Yuan Wang, Christopher Schatschneider, Pradeep G. Bhide
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引用次数: 0

摘要

导言脆弱X综合征是一种遗传性X连锁疾病,与智力障碍有关,从儿童时期开始并持续终生。其症状与自闭症谱系障碍重叠,且主要影响男性。因此,FXS 研究倾向于分析雄性的社会行为,而对其他行为特征,尤其是雌性行为特征的了解则存在空白。结果我们的行为测定显示了运动过动症、运动冲动、接近-回避测定中 "接近 "行为的增加以及筑巢行为的缺陷。对大脑神经递质含量的分析表明,纹状体中的 GABA、谷氨酸和血清素含量存在缺陷。腹侧纹状体的 RNA 测序揭示了与神经传递以及动机和药物使用途径相关的表达变化。总之,我们的研究确定了特定行为、神经递质和基因表达表型的性别差异,基因组富集分析确定了与动机和药物奖赏相关的通路的显著富集。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Behavioral, neurotransmitter and transcriptomic analyses in male and female Fmr1 KO mice
IntroductionFragile X syndrome is an inherited X-linked disorder associated with intellectual disabilities that begin in childhood and last a lifetime. The symptoms overlap with autism spectrum disorder, and the syndrome predominantly affects males. Consequently, FXS research tends to favor analysis of social behaviors in males, leaving a gap in our understanding of other behavioral traits, especially in females.MethodsWe used a mouse model of FXS to analyze developmental, behavioral, neurochemical, and transcriptomic profiles in males and females.ResultsOur behavioral assays demonstrated locomotor hyperactivity, motor impulsivity, increased “approach” behavior in an approach-avoidance assay, and deficits in nest building behavior. Analysis of brain neurotransmitter content revealed deficits in striatal GABA, glutamate, and serotonin content. RNA sequencing of the ventral striatum unveiled expression changes associated with neurotransmission as well as motivation and substance use pathways. Sex differences were identified in nest building behavior, striatal neurotransmitter content, and ventral striatal gene expression.DiscussionIn summary, our study identified sex differences in specific behavioral, neurotransmitter, and gene expression phenotypes and gene set enrichment analysis identified significant enrichment of pathways associated with motivation and drug reward.
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来源期刊
Frontiers in Behavioral Neuroscience
Frontiers in Behavioral Neuroscience BEHAVIORAL SCIENCES-NEUROSCIENCES
CiteScore
4.70
自引率
3.30%
发文量
506
审稿时长
6-12 weeks
期刊介绍: Frontiers in Behavioral Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the neural mechanisms underlying behavior. Field Chief Editor Nuno Sousa at the Instituto de Pesquisa em Ciências da Vida e da Saúde (ICVS) is supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide. This journal publishes major insights into the neural mechanisms of animal and human behavior, and welcomes articles studying the interplay between behavior and its neurobiological basis at all levels: from molecular biology and genetics, to morphological, biochemical, neurochemical, electrophysiological, neuroendocrine, pharmacological, and neuroimaging studies.
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