Work

Elevated Regulator of G Protein Signaling 8 (Rgs8) Expression in Cerebellar Purkinje Cells of a Non-Manifesting SCA14 Murine Line

Year: 2025

Type: article

Abstract: 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 (PKCγ), 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 PKCγ-Gly118Asp (G118D) mutation, located in the protein’s 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 PKCγ-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 PKCγ-G118D mice suggests molecular adaptations that may underlie the non-manifesting phenotype, offering insight into the subclinical SCA14 pathophysiology.

Source: Journal of Integrative Neuroscience

DOI: 10.31083/jin40839

Authors: Qin-Wei Wu, Josef P. Kapfhammer

Institutions: Anhui University, University of Basel

Language: English

Topic: Genetic Neurodegenerative Diseases

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,900