Cellular and Molecular Research Center, Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran 1449614535, Iran.
Department of Human Anatomy and Cell Science, The Children's Hospital Research Institute of Manitoba (CHRIM), Max Rady College of Medicine, Rady Faculty of Health science, University of Manitoba, Winnipeg, MB R3E 0J9, Canada.
Int J Mol Sci. 2020 Apr 21;21(8):2914. doi: 10.3390/ijms21082914.
A spontaneous mutation in the lysosomal acid phosphatase () enzyme (: naked-ataxia) in experimental mice results in delayed hair appearance and severe cytoarchitectural impairments of the cerebellum, such as a Purkinje cell (PC) migration defect. In our previous investigation, our team showed that Acp2 expression plans a significant role in cerebellar development. On the other hand, the dopaminergic system is also a player in central nervous system (CNS) development, including cerebellar structure and function. In the current investigation, we have explored how can be involved in the regulation of the dopaminergic pathway in the cerebellum via the regulation of dopamine receptor expression and patterning. We provided evidence about the distribution of different dopamine receptors in the developing cerebellum by comparing the expression of dopamine receptors on postnatal days (P) 5 and 17 between mice and wild-type (wt) littermates. To this aim, immunohistochemistry and Western blot analysis were conducted using five antibodies against dopamine receptors (DRD1, -2, -3, -4, and -5) accompanied by RNAseq data. Our results revealed that DRD1, -3, and -4 gene expressions significantly increased in cerebella but not in wt, while gene expressions of all 5 receptors were evident in PCs of both wt and cerebella. DRD3 was strongly expressed in the PCs' somata and cerebellar nuclei neurons at P17 in mice, which was comparable to the expression levels in the cerebella of wt littermates. In addition, DRD3 was expressed in scattered cells in a granular layer reminiscent of Golgi cells and was observed in the wt cerebella but not in mice. DRD4 was expressed in a subset of PCs and appeared to align with the unique parasagittal stripes pattern. This study contributes to our understanding of alterations in the expression pattern of DRDs in the cerebellum of mice in comparison to their wt littermates, and it highlights the role of in regulating the dopaminergic system.
实验小鼠溶酶体酸性磷酸酶（）酶（裸共济失调）中的自发突变导致毛发出现延迟和小脑严重的细胞结构损伤，如浦肯野细胞（PC）迁移缺陷。在我们之前的研究中，我们的团队表明 Acp2 表达在小脑发育中起着重要作用。另一方面，多巴胺能系统也是中枢神经系统（CNS）发育的参与者，包括小脑结构和功能。在当前的研究中，我们探索了如何通过调节多巴胺受体表达和模式来参与小脑多巴胺能途径的调节。我们通过比较 5 天和 17 天龄的突变小鼠和野生型（wt）同窝仔鼠之间的多巴胺受体表达，提供了不同多巴胺受体在发育中小脑分布的证据。为此，我们使用针对多巴胺受体（DRD1、-2、-3、-4 和-5）的五种抗体进行了免疫组织化学和 Western blot 分析，并结合 RNAseq 数据。我们的结果表明，突变小鼠小脑中 DRD1、-3 和-4 基因表达显著增加，但 wt 中则没有，而 wt 和突变小鼠小脑中的所有 5 种受体基因表达均明显。在突变小鼠的 P17 时，DRD3 在 PCs 体和小脑核神经元中强烈表达，与 wt 同窝仔鼠的表达水平相当。此外，DRD3 在颗粒层中散布的细胞中表达，类似于高尔基细胞，在 wt 小脑中有表达，但在突变小鼠中则没有。DRD4 在一小部分 PCs 中表达，似乎与独特的旁矢状条纹模式对齐。本研究有助于我们理解突变小鼠小脑中 DRD 表达模式的变化，并强调了 在调节多巴胺能系统中的作用。
