{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:10:46Z","timestamp":1760159446857,"version":"build-2065373602"},"reference-count":16,"publisher":"IMR Press","issue":"9","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003995","name":"Anhui Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["2408085QH277"],"award-info":[{"award-number":["2408085QH277"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Natural Science Research Project of Anhui Educational Committee","award":["2024AH050075"],"award-info":[{"award-number":["2024AH050075"]}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["310030_189083"],"award-info":[{"award-number":["310030_189083"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"name":"State Scholarship Fund of China Scholarship Council, Ministry of Education of the People\u2019s Republic of China"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Integr. Neurosci."],"abstract":"<jats:p>Background: Spinocerebellar ataxia (SCA) is an autosomal dominant neurodegenerative disorder marked by progressive loss of cerebellar function. Over 40 genetically defined SCA subtypes have been identified, arising from mechanisms such as cytosine-adenine-guanine (CAG) trinucleotide repeat expansions, point mutations, and gene deletions. Spinocerebellar ataxia type 14 (SCA14) stems from mutations to the protein kinase C gamma (PRKCG) gene, which codes for protein kinase C gamma (PKC\u03b3), a signaling protein predominantly expressed in cerebellar Purkinje cells. Although the genetic basis of SCA14 is well established, the mechanisms driving Purkinje cell dysfunction remain poorly understood. Notably, transgenic mice expressing the common PKC\u03b3-Gly118Asp (G118D) mutation, located in the protein\u2019s regulatory domain, do not exhibit an overt disease phenotype, raising questions about potential compensatory changes at the molecular level. Methods: We examined the expression of regulator of G protein signaling 8 (Rgs8), a molecule implicated in SCA-related pathways. Organotypic slice cultures and primary cerebellar cell cultures were generated in vitro to assess Purkinje cells from the non-manifesting PKC\u03b3-G118D transgenic mouse line. Results: A significant increase in Rgs8 expression was observed in both slice cultures and primary cerebellar cell cultures derived from the non-manifesting SCA14 mouse line. Conclusions: Elevated Rgs8 expression in Purkinje cells from symptom-free PKC\u03b3-G118D mice suggests molecular adaptations that may underlie the non-manifesting phenotype, offering insight into the subclinical SCA14 pathophysiology.<\/jats:p>","DOI":"10.31083\/jin40839","type":"journal-article","created":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T04:40:06Z","timestamp":1760157606000},"source":"Crossref","is-referenced-by-count":0,"title":["Elevated Regulator of G Protein Signaling 8 (Rgs8) Expression in Cerebellar Purkinje Cells of a Non-Manifesting SCA14 Murine Line"],"prefix":"10.31083","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7561-308X","authenticated-orcid":true,"given":"Qin-Wei","family":"Wu","sequence":"first","affiliation":[{"name":"Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, School of Life Sciences, Anhui University, 230601 Hefei, Anhui, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2404-5778","authenticated-orcid":true,"given":"Josef P.","family":"Kapfhammer","sequence":"first","affiliation":[{"name":"Institute of Anatomy, Department of Biomedicine, University of Basel, 4056 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Klockgether T, Mariotti C, Paulson HL. Spinocerebellar ataxia. Nature Reviews. Disease Primers. 2019; 5: 24.","DOI":"10.1038\/s41572-019-0074-3"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Seidel K, Siswanto S, Brunt ERP, den Dunnen W, Korf HW, R\u00fcb U. Brain pathology of spinocerebellar ataxias. Acta Neuropathologica. 2012; 124: 1\u201321.","DOI":"10.1007\/s00401-012-1000-x"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Serra HG, Duvick L, Zu T, Carlson K, Stevens S, Jorgensen N, et al. RORalpha-mediated Purkinje cell development determines disease severity in adult SCA1 mice. Cell. 2006; 127: 697\u2013708.","DOI":"10.1016\/j.cell.2006.09.036"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Wu QW, Kapfhammer JP. The Emerging Key Role of the mGluR1-PKC\u03b3 Signaling Pathway in the Pathogenesis of Spinocerebellar Ataxias: A Neurodevelopmental Viewpoint. International Journal of Molecular Sciences. 2022; 23: 9169.","DOI":"10.3390\/ijms23169169"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Wilke C, Bender F, Hayer SN, Brockmann K, Sch\u00f6ls L, Kuhle J, et al. Serum neurofilament light is increased in multiple system atrophy of cerebellar type and in repeat-expansion spinocerebellar ataxias: a pilot study. Journal of Neurology. 2018; 265: 1618\u20131624.","DOI":"10.1007\/s00415-018-8893-9"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Wijekoon N, Gonawala L, Ratnayake P, Sirisena D, Gunasekara H, Dissanayake A, et al. Serum metabolomic signatures of patients with rare neurogenetic diseases: an insight into potential biomarkers and treatment targets. Frontiers in Molecular Neuroscience. 2025; 17: 1482999.","DOI":"10.3389\/fnmol.2024.1482999"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Wu QW, Kapfhammer JP. Modulation of Increased mGluR1 Signaling by RGS8 Protects Purkinje Cells From Dendritic Reduction and Could Be a Common Mechanism in Diverse Forms of Spinocerebellar Ataxia. Frontiers in Cell and Developmental Biology. 2021; 8: 569889.","DOI":"10.3389\/fcell.2020.569889"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Ingram M, Wozniak EAL, Duvick L, Yang R, Bergmann P, Carson R, et al. Cerebellar Transcriptome Profiles of ATXN1 Transgenic Mice Reveal SCA1 Disease Progression and Protection Pathways. Neuron. 2016; 89: 1194\u20131207.","DOI":"10.1016\/j.neuron.2016.02.011"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Gatchel JR, Watase K, Thaller C, Carson JP, Jafar-Nejad P, Shaw C, et al. The insulin-like growth factor pathway is altered in spinocerebellar ataxia type 1 and type 7. Proceedings of the National Academy of Sciences of the United States of America. 2008; 105: 1291\u20131296.","DOI":"10.1073\/pnas.0711257105"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Liu Q, Huang S, Yin P, Yang S, Zhang J, Jing L, et al. Cerebellum-enriched protein INPP5A contributes to selective neuropathology in mouse model of spinocerebellar ataxias type 17. Nature Communications. 2020; 11: 1101.","DOI":"10.1038\/s41467-020-14931-8"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Verbeek DS, Warrenburg BPCVD, Hennekam FAM, Dooijes D, Ippel PF, Verschuuren-Bemelmans CC, et al. Gly118Asp is a SCA14 founder mutation in the Dutch ataxia population. Human Genetics. 2005; 117: 88\u201391.","DOI":"10.1007\/s00439-005-1278-z"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Shimobayashi E, Kapfhammer JP. Increased biological activity of protein Kinase C gamma is not required in Spinocerebellar ataxia 14. Molecular Brain. 2017; 10: 34.","DOI":"10.1186\/s13041-017-0313-z"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Kapfhammer JP, Gugger OS. The analysis of purkinje cell dendritic morphology in organotypic slice cultures. Journal of Visualized Experiments. 2012; 3637.","DOI":"10.3791\/3637"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Wu QW, Wang K, Kapfhammer JP. SCA14-Associated PKC\u03b3-G118D Mutant Exhibits a Detrimental Effect on Cerebellar Purkinje Cell Dendritic Growth. International Journal of Molecular Sciences. 2025; 26: 3688.","DOI":"10.3390\/ijms26083688"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Wu QW, Kapfhammer JP. CRISPR-Cas13-Mediated Knockdown of Regulator of G-Protein Signaling 8 (RGS8) Does Not Affect Purkinje Cell Dendritic Development. Frontiers in Cell and Developmental Biology. 2022; 10: 854273.","DOI":"10.3389\/fcell.2022.854273"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Kapfhammer JP, Shimobayashi E. Viewpoint: spinocerebellar ataxias as diseases of Purkinje cell dysfunction rather than Purkinje cell loss. Frontiers in Molecular Neuroscience. 2023; 16: 1182431.","DOI":"10.3389\/fnmol.2023.1182431"}],"container-title":["Journal of Integrative Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/JIN\/24\/9\/10.31083\/JIN40839","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T04:40:44Z","timestamp":1760157644000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/JIN\/24\/9\/10.31083\/JIN40839"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,25]]},"references-count":16,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025]]}},"alternative-id":["S0219-6352(25)00979-9"],"URL":"https:\/\/doi.org\/10.31083\/jin40839","relation":{},"ISSN":["0219-6352","1757-448X"],"issn-type":[{"value":"0219-6352","type":"print"},{"value":"1757-448X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,25]]},"article-number":"40839"}}