Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, 38068 Rovereto, Italy.
Center for Mind/Brain Sciences (CIMeC), University of Trento, 38068 Rovereto, Italy.
Genes (Basel). 2020 Apr 1;11(4):384. doi: 10.3390/genes11040384.
Impaired function of GABAergic interneurons, and the subsequent alteration of excitation/inhibition balance, is thought to contribute to autism spectrum disorders (ASD). Altered numbers of GABAergic interneurons and reduced expression of GABA receptors has been detected in the brain of ASD subjects and mouse models of ASD. We previously showed a reduced expression of GABAergic interneuron markers parvalbumin (PV) and somatostatin (SST) in the forebrain of adult mice lacking the gene ( mice). Here, we extended this analysis to postnatal day (P) 30 by using in situ hybridization, immunohistochemistry, and quantitative RT-PCR to study the expression of GABAergic interneuron markers in the hippocampus and somatosensory cortex of and wild type (WT) mice. In addition, GABA receptor subunit mRNA expression was investigated by quantitative RT-PCR in the same brain regions of P30 and adult and WT mice. As observed in adult animals, PV and SST expression was decreased in forebrain of P30 mice. The expression of GABA receptor subunits (including the ASD-relevant ) was also altered in young and adult forebrain. Our results suggest that GABAergic neurotransmission deficits are already evident at P30, confirming that neurodevelopmental defects of GABAergic interneurons occur in the mouse model of ASD.
GABA 能中间神经元功能障碍，以及随后兴奋/抑制平衡的改变，被认为是导致自闭症谱系障碍（ASD）的原因。在 ASD 患者和 ASD 小鼠模型的大脑中，已经检测到 GABA 能中间神经元数量的改变和 GABA 受体表达的减少。我们之前曾表明，缺乏 基因（ 小鼠）的成年小鼠前脑中 GABA 能中间神经元标志物 Parvalbumin（PV）和 Somatostatin（SST）的表达减少。在这里，我们通过原位杂交、免疫组织化学和定量 RT-PCR 分析，将这种分析扩展到出生后第 30 天（P30），以研究 和野生型（WT）小鼠海马体和体感皮层中 GABA 能中间神经元标志物的表达。此外，我们还通过定量 RT-PCR 研究了同一脑区的 GABA 受体亚基 mRNA 表达。与成年动物观察到的情况一样，P30 小鼠前脑中的 PV 和 SST 表达减少。年轻和成年 前脑中 GABA 受体亚基（包括与 ASD 相关的 ）的表达也发生了改变。我们的研究结果表明，GABA 能神经传递缺陷在 P30 时就已经明显存在，证实了 GABA 能中间神经元的神经发育缺陷确实发生在 ASD 的 小鼠模型中。
