The Number of Chandelier and Basket Cells Are Differentially Decreased in Prefrontal Cortex in Autism

The Number of Chandelier and Basket Cells Are Differentially Decreased in Prefrontal Cortex in Autism
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DOI:
10.1093/cercor/bhw349
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发表时间:
2018-02-01
期刊:
影响因子:
3.7
通讯作者:
Martinez-Cerdeno, Veronica
Martinez-Cerdeno, Veronica
中科院分区:
医学2区
文献类型:
--
作者:
Ariza, Jeanelle;Rogers, Haille;Martinez-Cerdeno, Veronica

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一种中间神经元的改变被认为是自闭症患者大脑皮层兴奋/抑制平衡改变的来源。我们之前证明了自闭症患者前额皮质中表达小白蛋白(PV)的中间神经元数量减少。表达pv的中间神经元包括chandelier (Ch)和basket (Bsk)细胞。我们询问减少的PV+中间神经元是否同时影响自闭症患者的Ch细胞和Bsk细胞。缺乏单个标记物特异性标记Ch细胞或Bsk细胞是解决这一问题的障碍。我们设计了一种基于绒毛凝集素(VVA)表达差异的PV-Ch和PV-Bsk细胞鉴别方法。VVA与n -乙酰半乳糖胺结合,n -乙酰半乳糖胺存在于围绕某些细胞类型的神经元周围网络中,在细胞间通讯中起作用。n -乙酰半乳糖胺存在于Bsk周围的神经网络中,而不存在于Ch细胞中。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Ch细胞的数量持续减少,而Bsk细胞的数量则没有受到严重影响。这一发现扩大了我们对自闭症患者大脑皮层gaba能系统功能的理解,这将影响转化研究,为自闭症患者提供更好的治疗范例。
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.