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大麻素受体 1 型敲除小鼠海马神经元和突触形态改变。

Neuronal and synaptic morphological alterations in the hippocampus of cannabinoid receptor type 1 knockout mice.

机构信息

Universidad de Buenos Aires. Facultad de Medicina. 1° Unidad Académica del Departamento de Histología, Embriología, Biología Celular y Genética. Buenos Aires. Argentina., Buenos Aires, Argentina.

Instituto de Biología Celular y Neurociencia Prof. E. De Robertis (IBCN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina.

出版信息

J Neurosci Res. 2020 Nov;98(11):2245-2262. doi: 10.1002/jnr.24694. Epub 2020 Jul 30.

DOI:10.1002/jnr.24694
PMID:32729959
Abstract

Cannabinoid receptor type 1 (CB1R) modulates synaptic activity and is widely distributed in brain areas such as the hippocampus, cerebellum, cerebral cortex, and striatum, among others. CB1R is involved in processes such as memory, learning, motor coordination, and mood. Genetic deletion of CB1R causes behavioral alterations. In this work, we evaluated neuronal morphology and synaptic structure in the hippocampus of adult male CB1R knockout mice (CB1R ). Morphological changes in the CB1R hippocampus evidenced a decrease in the expression of cytoskeletal proteins neurofilaments 160 KDa, neurofilaments 200 KDa, and microtubule-associated protein 2. CA1 neurons showed decreased arborization and changes in synaptic structure such as lower thickness of postsynaptic density and a reduction in synaptophysin levels. Results obtained in the present work provide evidence of the participation of CB1R in the establishment of neuronal structure and networks that could have an important role in neuronal plasticity. In addition, these changes observed in CB1R could be correlated with behavioral alterations reported.

摘要

大麻素受体 1 型(CB1R)调节突触活动,广泛分布于大脑区域,如海马体、小脑、大脑皮层和纹状体等。CB1R 参与记忆、学习、运动协调和情绪等过程。CB1R 的基因缺失会导致行为改变。在这项工作中,我们评估了成年雄性 CB1R 敲除小鼠(CB1R)海马体中的神经元形态和突触结构。CB1R 海马体的形态变化表明细胞骨架蛋白神经丝 160 kDa、神经丝 200 kDa 和微管相关蛋白 2 的表达减少。CA1 神经元的树突分支减少,突触结构发生变化,如突触后密度变薄,突触小泡蛋白水平降低。本工作的结果提供了 CB1R 参与神经元结构和网络建立的证据,这可能在神经元可塑性中起重要作用。此外,在 CB1R 中观察到的这些变化可能与报道的行为改变有关。

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