Abstract:
Mothers exposed to infections during pregnancy disproportionally birth children who develop autism and schizophrenia, disorders associated with altered GABAergic function. The maternal immune activation (MIA) model recapitulates this risk factor, with many studies also reporting disruptions to GABAergic interneuron expression, protein, cellular density and function. However, it is unclear if there are species, sex, age, region, or GABAergic subtype specific vulnerabilities to MIA. Furthermore, to fully comprehend the impact of MIA on the GABAergic system a synthesised account of molecular, cellular, electrophysiological and behavioural findings was required. To this end we conducted a systematic review of GABAergic interneuron changes in the MIA model, focusing on the prefrontal cortex and hippocampus. We reviewed 102 articles that revealed robust changes in a number of GABAergic markers that present as gestationally-specific, region-specific and sometimes sex-specific. Disruptions to GABAergic markers coincided with distinct behavioural phenotypes, including memory, sensorimotor gating, anxiety, and sociability. Findings suggest the MIA model is a valid tool for testing novel therapeutics designed to recover GABAergic function and associated behaviour.
摘要:
怀孕期间暴露于感染的母亲不成比例地生育患有自闭症和精神分裂症的孩子,与GABA能功能改变相关的疾病。母体免疫激活(MIA)模型概括了这一危险因素,许多研究也报道了GABA能中间神经元表达的中断,蛋白质,细胞密度和功能。然而,尚不清楚是否有物种,性别,年龄,区域,或针对MIA的GABA能亚型特定漏洞。此外,为了充分理解MIA对GABA能系统的影响,细胞,需要电生理和行为检查结果。为此,我们对MIA模型中GABA能中间神经元的变化进行了系统评价,专注于前额叶皮层和海马体。我们回顾了102篇文章,这些文章揭示了许多GABA能标志物的强烈变化,这些标志物表现为妊娠特异性,地区特异性,有时性别特异性。对GABA能标记物的破坏与不同的行为表型相吻合,包括记忆,感觉运动门控,焦虑,和社交能力。研究结果表明,MIA模型是测试旨在恢复GABA能功能和相关行为的新型疗法的有效工具。