Genetic Ablation of Inositol 1,4,5-Trisphosphate Receptor Type 2 (IP(3)R2) Fails to Modify Disease Progression in a Mouse Model of Spinocerebellar Ataxia Type 3

• Type: Article in International Scientific Journal
• Date: 2023

Authors

Cunha-Garcia, D (Author) Other; Monteiro-Fernandes, D (Author) Other; Correia, JS (Author) Other; Neves-Carvalho, A (Author) Other; Vilaca-Ferreira, AC (Author) Other; Guerra-Gomes, S (Author) Other; Viana, JF (Author) Other; Oliveira, JF (Author) Other; Teixeira-Castro, A (Author) Other; Maciel, P (Author) Other; Duarte-Silva, S (Author) Other

Journal

Title: International Journal Of Molecular Sciences

Vol. 24 No. 2335

ISSN: 1661-6596

Publisher: MDPI

Indexing

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Other information

Authenticus ID: P-00Y-R9F

DOI: 10.3390/ijms241310606

Abstract (EN): Spinocerebellar ataxia type 3 (SCA3) is a rare neurodegenerative disease caused by an abnormal polyglutamine expansion within the ataxin-3 protein (ATXN3). This leads to neurodegeneration of specific brain and spinal cord regions, resulting in a progressive loss of motor function. Despite neuronal death, non-neuronal cells, including astrocytes, are also involved in SCA3 pathogenesis. Astrogliosis is a common pathological feature in SCA3 patients and animal models of the disease. However, the contribution of astrocytes to SCA3 is not clearly defined. Inositol 1,4,5-trisphosphate receptor type 2 (IP(3)R2) is the predominant IP3R in mediating astrocyte somatic calcium signals, and genetically ablation of IP(3)R2 has been widely used to study astrocyte function. Here, we aimed to investigate the relevance of IP(3)R2 in the onset and progression of SCA3. For this, we tested whether IP(3)R2 depletion and the consecutive suppression of global astrocytic calcium signalling would lead to marked changes in the behavioral phenotype of a SCA3 mouse model, the CMVMJD135 transgenic line. This was achieved by crossing IP(3)R2 null mice with the CMVMJD135 mouse model and performing a longitudinal behavioral characterization of these mice using well-established motor-related function tests. Our results demonstrate that IP(3)R2 deletion in astrocytes does not modify SCA3 progression.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 22