Behavioral regulation by perineuronal nets in the prefrontal cortex of the CNTNAP2 mouse model of autism spectrum disorder.
Behavioral regulation by perineuronal nets in the prefrontal cortex of the CNTNAP2 mouse model of autism spectrum disorder.
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DOI：
10.3389/fnbeh.2023.1114789
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发表时间：
2023
影响因子：
3
通讯作者：
中科院分区：
文献类型：
--
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自闭症谱系障碍（ASD）是由中枢神经系统发育的改变引起的，表现为社会互动缺陷和限制性和重复性行为。表达小清蛋白（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，神经元束膜网（perineuronal nets，PNN），包裹PV表达神经元的特化细胞外基质结构，也可能被改变，这会损害神经元功能和对氧化应激的敏感性。特别是，调节几个核心自闭症特征的前额叶皮层（PFC）依赖于PNN和PV表达细胞以及其他神经回路元件的正常组织。因此，我们研究了CNTNAP 2敲除ASD小鼠模型的前额叶皮质中PNN和PV表达细胞是否发生改变，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CNTNAP 2小鼠中PNN、PV表达细胞和包裹PV表达细胞的PNN过表达。通过在CNTNAP 2突变小鼠中注射软骨素酶ABC从前额叶皮层（PFC）瞬时消化PNN，挽救了一些社会互动缺陷，但没有限制和重复行为。这些发现表明，PFC中PNN和PV的神经生物学调节有助于神经系统疾病（包括自闭症）的社会互动行为。
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.
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影响因子：
4.7
作者：
Canitano R;Pallagrosi M
通讯作者：
Pallagrosi M
影响因子：
14.5
作者：
Bailey, A;Luthert, P;Lantos, P
通讯作者：
Lantos, P
影响因子：
4.7
作者：
Beggiato, Anita;Peyre, Hugo;Delorme, Richard
通讯作者：
Delorme, Richard
影响因子：
3.3
作者：
Bukalo, O;Schachner, M;Dityatev, A
通讯作者：
Dityatev, A
DOI：
10.1073/pnas.0609440103
发表时间：
2006-12-26
影响因子：
11.1
作者：
Cho, R. Y.;Konecky, R. O.;Carter, C. S.
通讯作者：
Carter, C. S.