Gandhi Tanya, Liu Chin-Chi, Adeyelu Tolulope T, Canepa Cade R, Lee Charles C
Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA, United States.
Department of Veterinary Clinical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA, United States.
Front Behav Neurosci. 2023 Mar 14;17:1114789. doi: 10.3389/fnbeh.2023.1114789. eCollection 2023.
Autism spectrum disorders (ASDs) arise from altered development of the central nervous system, and manifest behaviorally as social interaction deficits and restricted and repetitive behaviors. Alterations to parvalbumin (PV) expressing interneurons have been implicated in the neuropathological and behavioral deficits in autism. In addition, perineuronal nets (PNNs), specialized extracellular matrix structures that enwrap the PV-expressing neurons, also may be altered, which compromises neuronal function and susceptibility to oxidative stress. In particular, the prefrontal cortex (PFC), which regulates several core autistic traits, relies on the normal organization of PNNs and PV-expressing cells, as well as other neural circuit elements. Consequently, we investigated whether PNNs and PV-expressing cells were altered in the PFC of the CNTNAP2 knockout mouse model of ASD and whether these contributed to core autistic-like behaviors in this model system. We observed an overexpression of PNNs, PV-expressing cells, and PNNs enwrapping PV-expressing cells in adult CNTNAP2 mice. Transient digestion of PNNs from the prefrontal cortex (PFC) by injection of chondroitinase ABC in CNTNAP2 mutant mice rescued some of the social interaction deficits, but not the restricted and repetitive behaviors. These findings suggest that the neurobiological regulation of PNNs and PVs in the PFC contribute to social interaction behaviors in neurological disorders including autism.
自闭症谱系障碍（ASD）源于中枢神经系统发育异常，行为表现为社交互动缺陷以及局限的重复行为。表达小白蛋白（PV）的中间神经元的改变与自闭症的神经病理学和行为缺陷有关。此外，神经周网（PNN），即包裹表达PV的神经元的特殊细胞外基质结构，也可能发生改变，这会损害神经元功能以及对氧化应激的易感性。特别是，调节多种核心自闭症特征的前额叶皮质（PFC）依赖于PNN和表达PV的细胞以及其他神经回路元件的正常组织。因此，我们研究了在ASD的接触蛋白相关蛋白2（CNTNAP2）基因敲除小鼠模型的PFC中PNN和表达PV的细胞是否发生改变，以及这些是否导致了该模型系统中的核心自闭症样行为。我们观察到成年CNTNAP2小鼠中PNN、表达PV的细胞以及包裹表达PV细胞的PNN均有过表达。通过向CNTNAP2突变小鼠的前额叶皮质（PFC）注射软骨素酶ABC对PNN进行短暂消化，挽救了一些社交互动缺陷，但没有挽救局限的重复行为。这些发现表明，PFC中PNN和PV的神经生物学调节有助于包括自闭症在内的神经疾病中的社交互动行为。
