Alteration of the Dopamine Receptors' Expression in the Cerebellum of the Lysosomal Acid Phosphatase 2 Mutant (Naked-Ataxia ( NAX )) Mouse.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, [2000-
    • Subject Terms:
      Gene Expression* ; Mutation*; Acid Phosphatase/*genetics ; Cerebellum/*metabolism ; Receptors, Dopamine/*genetics; Acid Phosphatase/metabolism ; Animals ; Autophagy/genetics ; Immunohistochemistry ; Mice ; Purkinje Cells/metabolism ; Receptors, Dopamine/metabolism
    • Abstract:
      A spontaneous mutation in the lysosomal acid phosphatase ( Acp2 ) enzyme ( nax : 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 Acp2 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 nax 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 nax cerebella but not in wt, while gene expressions of all 5 receptors were evident in PCs of both wt and nax cerebella. DRD3 was strongly expressed in the PCs' somata and cerebellar nuclei neurons at P17 in nax 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 nax 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 nax mice in comparison to their wt littermates, and it highlights the role of Acp2 in regulating the dopaminergic system.
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    • Grant Information:
      RGPIN-2018-06040 Natural Sciences and Engineering Research Council of Canada
    • Contributed Indexing:
      Keywords: Acp2; Purkinje cells; autophagy; cerebellum; dopamine receptors
    • Accession Number:
      0 (Receptors, Dopamine)
      EC 3.1.3.2 (Acid Phosphatase)
      EC 3.1.3.2 (Acp2 protein, mouse)
    • Publication Date:
      Date Created: 20200425 Date Completed: 20210125 Latest Revision: 20231111
    • Publication Date:
      20231215
    • Accession Number:
      PMC7215910
    • Accession Number:
      10.3390/ijms21082914
    • Accession Number:
      32326360