Department of Pathology and Laboratory Medicine, UC Davis School of Medicine; Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children, Sacramento, CA 95817, USA.
MIND Institute, UC Davis Medical Center, UC Davis School of Medicine, Sacramento, CA 95817, USA.
Cereb Cortex. 2021 May 10;31(6):2944-2951. doi: 10.1093/cercor/bhaa402.
An alteration in the balance of excitation-inhibition has been proposed as a common characteristic of the cerebral cortex in autism, which may be due to an alteration in the number and/or function of the excitatory and/or inhibitory cells that form the cortical circuitry. We previously found a decreased number of the parvalbumin (PV)+ interneuron known as Chandelier (Ch) cell in the prefrontal cortex in autism. This decrease could result from a decreased number of Ch cells, but also from decreased PV protein expression by Ch cells. To further determine if Ch cell number is altered in autism, we quantified the number of Ch cells following a different approach and different patient cohort than in our previous studies. We quantified the number of Ch cell cartridges-rather than Ch cell somata-that expressed GAT1-rather than PV. Specifically, we quantified GAT1+ cartridges in prefrontal areas BA9, BA46, and BA47 of 11 cases with autism and 11 control cases. We found that the density of GAT1+ cartridges was decreased in autism in all areas and layers. Whether this alteration is cause or effect remains unclear but could result from alterations that take place during cortical prenatal and/or postnatal development.
兴奋性-抑制性平衡的改变被认为是自闭症大脑皮层的共同特征,这可能是由于形成皮层回路的兴奋性和/或抑制性细胞的数量和/或功能发生改变所致。我们之前发现自闭症患者前额叶皮层中的 Parvalbumin(PV)+中间神经元(称为 Chandelier(Ch)细胞)数量减少。这种减少可能是由于 Ch 细胞数量减少,也可能是由于 Ch 细胞的 PV 蛋白表达减少所致。为了进一步确定自闭症中 Ch 细胞数量是否发生改变,我们采用了与之前研究不同的方法和不同的患者队列来定量 Ch 细胞的数量。我们定量了表达 GAT1 的 Ch 细胞的细胞体——而不是 PV——的 Ch 细胞盒的数量。具体来说,我们在自闭症和 11 例对照病例的前额叶区域 BA9、BA46 和 BA47 中定量了 GAT1+盒的数量。我们发现,自闭症患者所有区域和层的 GAT1+盒密度均降低。这种改变是原因还是结果尚不清楚,但可能是由于皮质产前和/或产后发育过程中的改变所致。