Exposure to GABA(A) Receptor Antagonist Picrotoxin in Pregnant Mice Causes Autism-Like Behaviors and Aberrant Gene Expression in Offspring.
Exposure to GABA(A) Receptor Antagonist Picrotoxin in Pregnant Mice Causes Autism-Like Behaviors and Aberrant Gene Expression in Offspring.
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DOI：
10.3389/fpsyt.2022.821354
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发表时间：
2022
影响因子：
4.7
通讯作者：
Ikeda K
中科院分区：
文献类型：
--
作者：
Kotajima-Murakami H;Hagihara H;Sato A;Hagino Y;Tanaka M;Katoh Y;Nishito Y;Takamatsu Y;Uchino S;Miyakawa T;Ikeda K
自闭症谱系障碍（ASD）是一种神经发育障碍，其特征在于社会互动和限制/重复行为的障碍。神经递质γ-氨基丁酸（GABA）通过GABAA受体信号传导在未成熟脑中的神经回路发育中起着关键作用。成熟大脑中的兴奋/抑制失衡已被研究为ASD的病理生理机制。然而，是否以及如何干扰GABA信号在胚胎中引起的GABAA受体抑制剂导致ASD样病理生理学知之甚少。本研究探讨是否暴露于GABAA受体拮抗剂印防己毒素导致ASD样的病理生理学在后代进行行为测试，从少年期到成年期，并在成熟的小鼠大脑中进行基因表达分析。在这里，我们发现，产前暴露于印防己毒素的雄性小鼠在青春期和成年期的社会互动测试中表现出主动互动时间的减少。基因表达分析表明，印防己毒素暴露的雄性小鼠表现出显着增加的气味受体的基因表达。加权基因共表达网络分析表明，社会相互作用和丰富的“气味结合”途径基因模块之间有很强的相关性。我们的研究结果表明，在胚胎期暴露于GABAA受体抑制剂诱导ASD样行为，气味功能的损害可能导致后代的社会缺陷。
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is characterized by impairments in social interaction and restricted/repetitive behaviors. The neurotransmitter γ-aminobutyric acid (GABA) through GABAA receptor signaling in the immature brain plays a key role in the development of neuronal circuits. Excitatory/inhibitory imbalance in the mature brain has been investigated as a pathophysiological mechanism of ASD. However, whether and how disturbances of GABA signaling in embryos that are caused by GABAA receptor inhibitors cause ASD-like pathophysiology are poorly understood. The present study examined whether exposure to the GABAA receptor antagonist picrotoxin causes ASD-like pathophysiology in offspring by conducting behavioral tests from the juvenile period to adulthood and performing gene expression analyses in mature mouse brains. Here, we found that male mice that were prenatally exposed to picrotoxin exhibited a reduction of active interaction time in the social interaction test in both adolescence and adulthood. The gene expression analyses showed that picrotoxin-exposed male mice exhibited a significant increase in the gene expression of odorant receptors. Weighted gene co-expression network analysis showed a strong correlation between social interaction and enrichment of the “odorant binding” pathway gene module. Our findings suggest that exposure to a GABAA receptor inhibitor during the embryonic period induces ASD-like behavior, and impairments in odorant function may contribute to social deficits in offspring.
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影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
4.9
作者：
Gogolla, Nadine;LeBlanc, Jocelyn J.;Quast, Kathleen B.;Sudhof, Thomas C.;Fagiolini, Michela;Hensch, Takao K.
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影响因子：
4.8
作者：
Grabrucker S;Haderspeck JC;Sauer AK;Kittelberger N;Asoglu H;Abaei A;Rasche V;Schön M;Boeckers TM;Grabrucker AM
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Grabrucker AM
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影响因子：
6.7
作者：
Ferri SL;Abel T;Brodkin ES
通讯作者：
Brodkin ES
影响因子：
3.7
作者：
Jew CP;Wu CS;Sun H;Zhu J;Huang JY;Yu D;Justice NJ;Lu HC
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Lu HC