Brandenburg Cheryl, Blatt Gene J
Hussman Institute for Autism, Baltimore, MD, United States.
Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, United States.
Front Mol Neurosci. 2022 Apr 13;15:838918. doi: 10.3389/fnmol.2022.838918. eCollection 2022.
Genetic variance in autism spectrum disorder (ASD) is often associated with mechanisms that broadly fall into the category of neuroplasticity. Parvalbumin positive neurons and their surrounding perineuronal nets (PNNs) are important factors in critical period plasticity and have both been implicated in ASD. PNNs are found in high density within output structures of the cerebellum and basal ganglia, two regions that are densely connected to many other brain areas and have the potential to participate in the diverse array of symptoms present in an ASD diagnosis. The dentate nucleus (DN) and globus pallidus (GP) were therefore assessed for differences in PNN expression in human postmortem ASD brain tissue. While Purkinje cell loss is a consistent neuropathological finding in ASD, in this cohort, the Purkinje cell targets within the DN did not show differences in number of cells with or without a PNN. However, the density of parvalbumin positive neurons with a PNN were significantly reduced in the GP internus and externus of ASD cases, which was not dependent on seizure status. It is unclear whether these alterations manifest during development or are a consequence of activity-dependent mechanisms that lead to altered network dynamics later in life.
自闭症谱系障碍（ASD）中的遗传变异通常与广泛属于神经可塑性范畴的机制相关。小白蛋白阳性神经元及其周围的神经元周网（PNN）是关键期可塑性的重要因素，二者均与ASD有关。在小脑和基底神经节的输出结构中发现PNN的高密度分布，这两个区域与许多其他脑区紧密相连，并且有可能参与ASD诊断中出现的各种症状。因此，研究人员评估了人类死后ASD脑组织中齿状核（DN）和苍白球（GP）的PNN表达差异。虽然浦肯野细胞丢失是ASD中一致的神经病理学发现，但在该队列中，DN内的浦肯野细胞靶点在有或没有PNN的细胞数量上没有差异。然而，ASD病例的内侧苍白球和外侧苍白球中带有PNN的小白蛋白阳性神经元密度显著降低，这与癫痫发作状态无关。目前尚不清楚这些改变是在发育过程中出现的，还是由活动依赖机制导致的结果，这些机制会在生命后期导致网络动态改变。
