Sex-specific behavioural deficits in adulthood following acute activation of the GABAA receptor in the neonatal mouse.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
Ane Goikolea-Vives, Cathy Fernandes, Michael S C Thomas, Claire Thornton, Helen B Stolp
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Abstract

Introduction: Sex differences exist in the prevalence of neurodevelopmental disorders (NDDs). Part of the aetiology of NDDs has been proposed to be alterations in the balance between excitatory and inhibitory neurotransmission, leading to the question of whether males and females respond differently to altered neurotransmitter balance. We investigated whether pharmacological alteration of GABAA signalling in early development results in sex-dependent changes in adult behaviours associated with NDDs.

Methods: Male and female C57BL/6J mice received intraperitoneal injections of 0.5mg/kg muscimol or saline on postnatal days (P) 3-5 and were subjected to behavioural testing, specifically open field, light dark box, marble burying, sucralose preference, social interaction and olfactory habituation/dishabituation tests between P60-90.

Results: Early postnatal administration of muscimol resulted in reduced anxiety in the light dark box test in both male and female adult mice. Muscimol reduced sucralose preference in males, but not females, whereas female mice showed reduced social behaviours. Regional alterations in cortical thickness were observed in the weeks following GABAA receptor activation, pointing to an evolving structural difference in the brain underlying adult behaviour.

Conclusions: We conclude that activation of the GABAA receptor in the first week of life resulted in long-lasting changes in a range of behaviours in adulthood following altered neurodevelopment. Sex of the individual affected the nature and severity of these abnormalities, explaining part of the varied pathophysiology and neurodevelopmental diagnosis that derive from excitatory/inhibitory imbalance.

新生小鼠 GABAA 受体急性激活后成年期行为缺陷的性别特异性
导言:神经发育障碍(NDDs)的发病率存在性别差异。神经发育障碍的部分病因被认为是兴奋性和抑制性神经递质之间的平衡发生了改变,从而引发了男性和女性是否会对神经递质平衡的改变做出不同反应的问题。我们研究了药物改变早期发育中的 GABAA 信号是否会导致与 NDDs 相关的成年行为发生性别依赖性变化:雄性和雌性C57BL/6J小鼠在出生后第3-5天腹腔注射0.5mg/kg麝香草酚或生理盐水,并在出生后第60-90天接受行为测试,特别是开阔地、光暗箱、大理石埋藏、蔗糖偏好、社会互动和嗅觉习惯化/减弱测试:结果:出生后早期服用麝香草酚可减少雄性和雌性成年小鼠在光暗箱测试中的焦虑。麝香草酚能降低雄性小鼠对蔗糖素(三氯蔗糖)的偏好,但不能降低雌性小鼠对蔗糖素(三氯蔗糖)的偏好。在 GABAA 受体激活后的几周内,观察到大脑皮层厚度发生了区域性变化,这表明成年小鼠行为背后的大脑结构差异在不断发展:我们得出的结论是,在小鼠出生后第一周激活 GABAA 受体会导致其成年后神经发育发生改变,从而引起一系列行为的长期变化。个体的性别会影响这些异常的性质和严重程度,从而部分解释了兴奋/抑制失衡导致的不同病理生理学和神经发育诊断。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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