Alteration of the Dopamine Receptors’ Expression in the Cerebellum of the Lysosomal Acid Phosphatase 2 Mutant (Naked–Ataxia (<i>NAX</i>)) Mouse
A spontaneous mutation in the lysosomal acid phosphatase (<i>Acp2</i>) enzyme (<i>nax</i>: 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 p...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-04-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/8/2914 |
| _version_ | 1797570008710119424 |
|---|---|
| author | Mehdi Mehdizadeh Niloufar Ashtari Xiaodan Jiao Maryam Rahimi Balaei Asghar Marzban Farshid Qiyami-Hour Jiming Kong Saeid Ghavami Hassan Marzban |
| author_facet | Mehdi Mehdizadeh Niloufar Ashtari Xiaodan Jiao Maryam Rahimi Balaei Asghar Marzban Farshid Qiyami-Hour Jiming Kong Saeid Ghavami Hassan Marzban |
| author_sort | Mehdi Mehdizadeh |
| collection | DOAJ |
| description | A spontaneous mutation in the lysosomal acid phosphatase (<i>Acp2</i>) enzyme (<i>nax</i>: 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 <i>Acp2</i> 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 <i>nax</i> 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 <i>nax</i> cerebella but not in wt, while gene expressions of all 5 receptors were evident in PCs of both wt and <i>nax</i> cerebella. DRD3 was strongly expressed in the PCs’ somata and cerebellar nuclei neurons at P17 in <i>nax</i> 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 <i>nax</i> 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 <i>nax</i> mice in comparison to their wt littermates, and it highlights the role of <i>Acp2</i> in regulating the dopaminergic system. |
| first_indexed | 2024-03-10T20:19:09Z |
| format | Article |
| id | doaj.art-46fd025facaf48058f52604cb4a4f105 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T20:19:09Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-46fd025facaf48058f52604cb4a4f1052023-11-19T22:18:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01218291410.3390/ijms21082914Alteration of the Dopamine Receptors’ Expression in the Cerebellum of the Lysosomal Acid Phosphatase 2 Mutant (Naked–Ataxia (<i>NAX</i>)) MouseMehdi Mehdizadeh0Niloufar Ashtari1Xiaodan Jiao2Maryam Rahimi Balaei3Asghar Marzban4Farshid Qiyami-Hour5Jiming Kong6Saeid Ghavami7Hassan Marzban8Cellular and Molecular Research Center, Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran 1449614535, IranDepartment 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, CanadaDepartment 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, CanadaDepartment 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, CanadaDepartment of Pediatrics, School of Medicine, Zanjan University of Medical Sciences, Zanjan 4513956111, IranCellular and Molecular Research Center, Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran 1449614535, IranCellular and Molecular Research Center, Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran 1449614535, IranCellular and Molecular Research Center, Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran 1449614535, IranCellular and Molecular Research Center, Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran 1449614535, IranA spontaneous mutation in the lysosomal acid phosphatase (<i>Acp2</i>) enzyme (<i>nax</i>: 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 <i>Acp2</i> 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 <i>nax</i> 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 <i>nax</i> cerebella but not in wt, while gene expressions of all 5 receptors were evident in PCs of both wt and <i>nax</i> cerebella. DRD3 was strongly expressed in the PCs’ somata and cerebellar nuclei neurons at P17 in <i>nax</i> 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 <i>nax</i> 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 <i>nax</i> mice in comparison to their wt littermates, and it highlights the role of <i>Acp2</i> in regulating the dopaminergic system.https://www.mdpi.com/1422-0067/21/8/2914dopamine receptorsPurkinje cellscerebellumautophagy<i>Acp2</i> |
| spellingShingle | Mehdi Mehdizadeh Niloufar Ashtari Xiaodan Jiao Maryam Rahimi Balaei Asghar Marzban Farshid Qiyami-Hour Jiming Kong Saeid Ghavami Hassan Marzban Alteration of the Dopamine Receptors’ Expression in the Cerebellum of the Lysosomal Acid Phosphatase 2 Mutant (Naked–Ataxia (<i>NAX</i>)) Mouse International Journal of Molecular Sciences dopamine receptors Purkinje cells cerebellum autophagy <i>Acp2</i> |
| title | Alteration of the Dopamine Receptors’ Expression in the Cerebellum of the Lysosomal Acid Phosphatase 2 Mutant (Naked–Ataxia (<i>NAX</i>)) Mouse |
| title_full | Alteration of the Dopamine Receptors’ Expression in the Cerebellum of the Lysosomal Acid Phosphatase 2 Mutant (Naked–Ataxia (<i>NAX</i>)) Mouse |
| title_fullStr | Alteration of the Dopamine Receptors’ Expression in the Cerebellum of the Lysosomal Acid Phosphatase 2 Mutant (Naked–Ataxia (<i>NAX</i>)) Mouse |
| title_full_unstemmed | Alteration of the Dopamine Receptors’ Expression in the Cerebellum of the Lysosomal Acid Phosphatase 2 Mutant (Naked–Ataxia (<i>NAX</i>)) Mouse |
| title_short | Alteration of the Dopamine Receptors’ Expression in the Cerebellum of the Lysosomal Acid Phosphatase 2 Mutant (Naked–Ataxia (<i>NAX</i>)) Mouse |
| title_sort | alteration of the dopamine receptors expression in the cerebellum of the lysosomal acid phosphatase 2 mutant naked ataxia i nax i mouse |
| topic | dopamine receptors Purkinje cells cerebellum autophagy <i>Acp2</i> |
| url | https://www.mdpi.com/1422-0067/21/8/2914 |
| work_keys_str_mv | AT mehdimehdizadeh alterationofthedopaminereceptorsexpressioninthecerebellumofthelysosomalacidphosphatase2mutantnakedataxiainaximouse AT niloufarashtari alterationofthedopaminereceptorsexpressioninthecerebellumofthelysosomalacidphosphatase2mutantnakedataxiainaximouse AT xiaodanjiao alterationofthedopaminereceptorsexpressioninthecerebellumofthelysosomalacidphosphatase2mutantnakedataxiainaximouse AT maryamrahimibalaei alterationofthedopaminereceptorsexpressioninthecerebellumofthelysosomalacidphosphatase2mutantnakedataxiainaximouse AT asgharmarzban alterationofthedopaminereceptorsexpressioninthecerebellumofthelysosomalacidphosphatase2mutantnakedataxiainaximouse AT farshidqiyamihour alterationofthedopaminereceptorsexpressioninthecerebellumofthelysosomalacidphosphatase2mutantnakedataxiainaximouse AT jimingkong alterationofthedopaminereceptorsexpressioninthecerebellumofthelysosomalacidphosphatase2mutantnakedataxiainaximouse AT saeidghavami alterationofthedopaminereceptorsexpressioninthecerebellumofthelysosomalacidphosphatase2mutantnakedataxiainaximouse AT hassanmarzban alterationofthedopaminereceptorsexpressioninthecerebellumofthelysosomalacidphosphatase2mutantnakedataxiainaximouse |