Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Developmental Disability Center, 713-8 Kamiya, Kasugai 480-0392, Japan.
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Biomolecules. 2023 Apr 27;13(5):763. doi: 10.3390/biom13050763.
22q11.2 deletion syndrome (22q11.2DS) is associated with a high risk of developing various psychiatric and developmental disorders, including schizophrenia and early-onset Parkinson's disease. Recently, a mouse model of this disease, Del(3.0Mb)/+, mimicking the 3.0 Mb deletion which is most frequently found in patients with 22q11.2DS, was generated. The behavior of this mouse model was extensively studied and several abnormalities related to the symptoms of 22q11.2DS were found. However, the histological features of their brains have been little addressed. Here we describe the cytoarchitectures of the brains of Del(3.0Mb)/+ mice. First, we investigated the overall histology of the embryonic and adult cerebral cortices, but they were indistinguishable from the wild type. However, the morphologies of individual neurons were slightly but significantly changed from the wild type counterparts in a region-specific manner. The dendritic branches and/or dendritic spine densities of neurons in the medial prefrontal cortex, nucleus accumbens, and primary somatosensory cortex were reduced. We also observed reduced axon innervation of dopaminergic neurons into the prefrontal cortex. Given these affected neurons function together as the dopamine system to control animal behaviors, the impairment we observed may explain a part of the abnormal behaviors of Del(3.0Mb)/+ mice and the psychiatric symptoms of 22q11.2DS.
22q11.2 缺失综合征(22q11.2DS)与多种精神和发育障碍的高风险相关,包括精神分裂症和早发性帕金森病。最近,生成了一种模拟患者中最常见的 22q11.2DS 3.0Mb 缺失的疾病小鼠模型 Del(3.0Mb)/+。对该小鼠模型的行为进行了广泛研究,发现了与 22q11.2DS 症状相关的几种异常。然而,其大脑的组织学特征尚未得到充分解决。在这里,我们描述了 Del(3.0Mb)/+ 小鼠大脑的细胞构筑。首先,我们研究了胚胎和成年大脑皮质的整体组织学,但它们与野生型没有区别。然而,从野生型对应的特定区域来看,个别神经元的形态略有但显著改变。内侧前额叶皮质、伏隔核和初级体感皮层中神经元的树突分支和/或树突棘密度降低。我们还观察到多巴胺能神经元进入前额叶皮层的轴突神经支配减少。鉴于这些受影响的神经元共同作为多巴胺系统来控制动物行为,我们观察到的损伤可能解释了 Del(3.0Mb)/+ 小鼠异常行为和 22q11.2DS 精神症状的一部分。