Department of Pathology and Laboratory Medicine, UC Davis; Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children Northern California, Sacramento, USA.
Department of Psychiatry and Behavioral Sciences, UC Davis, Sacramento, USA.
Cereb Cortex. 2018 Feb 1;28(2):411-420. doi: 10.1093/cercor/bhw349.
An interneuron alteration has been proposed as a source for the modified balance of excitation / inhibition in the cerebral cortex in autism. We previously demonstrated a decreased number of parvalbumin (PV)-expressing interneurons in prefrontal cortex in autism. PV-expressing interneurons include chandelier (Ch) and basket (Bsk) cells. We asked whether the decreased PV+ interneurons affected both Ch cells and Bsk cells in autism. The lack of single markers to specifically label Ch cells or Bsk cells presented an obstacle for addressing this question. We devised a method to discern between PV-Ch and PV-Bsk cells based on the differential expression of Vicia villosa lectin (VVA). VVA binds to N-acetylgalactosamine, that is present in the perineuronal net surrounding some cell types where it plays a role in intercellular communication. N-acetylgalactosamine is present in the perineuronal net surrounding Bsk but not Ch cells. We found that the number of Ch cells is consistently decreased in the prefrontal cortex of autistic (n = 10) when compared with control (n = 10) cases, while the number of Bsk cells is not as severely affected. This finding expand our understanding of GABAergic system functioning in the human cerebral cortex in autism, which will impact translational research directed towards providing better treatment paradigms for individuals with autism.
一种观点认为，自闭症患者大脑皮层中兴奋性/抑制性平衡的改变源自中间神经元的改变。我们先前已经证明，自闭症患者前额叶皮层中的 Parvalbumin（PV）表达中间神经元数量减少。PV 表达中间神经元包括 Chandelier（Ch）和 Basket（Bsk）细胞。我们想知道 PV+中间神经元数量的减少是否会影响自闭症患者的 Ch 细胞和 Bsk 细胞。缺乏能够特异性标记 Ch 细胞或 Bsk 细胞的单一标志物，给解决这个问题带来了困难。我们设计了一种方法，根据黑腹绒猴豆凝集素（VVA）的差异表达，来区分 PV-Ch 和 PV-Bsk 细胞。VVA 与 N-乙酰半乳糖胺结合，后者存在于一些细胞类型的周围神经丛中，在细胞间通讯中发挥作用。N-乙酰半乳糖胺存在于 Bsk 细胞的周围神经丛中，但不存在于 Ch 细胞周围。我们发现，与对照组（n=10）相比，自闭症患者（n=10）前额叶皮层中的 Ch 细胞数量持续减少，而 Bsk 细胞数量受影响较小。这一发现扩展了我们对自闭症患者大脑皮层中 GABA 能系统功能的理解，这将影响针对自闭症患者提供更好治疗方案的转化研究。
