Purkinje cell loss associated with specific ultrastructural alterations in a mouse model with transgenic expression of mutated ataxin-2

Authors

Keywords:

Ataxia, Spinocerebellar Ataxia type 2, ataxin-2, transgenic mice, polyglutamine disorders, Purkinje cells

Abstract

Introduction: The expression of ataxin-2 protein with an N-terminal expanded polyglutamine domain is the cause of Spinocerebellar Ataxia type 2 (SCA2), acting primarily on cerebellar Purkinje cells. The morphological study of cerebellar Purkinje cells expressing polyglutamine-expanded ataxin-2 might provide information on the pathogenic mechanisms underlying the disease process and contribute to the identification of potential therapeutic targets.

Objective: To identify changes in the cellularity and ultrastructure of Purkinje cells associated with the expression of polyglutamine-expanded ataxin-2.

Material and Methods: Three groups of transgenic mice (F066) aged two, five, and 12 months, expressing the polyglutamine-expanded ataxin-2 and a group of 12-month-old wild type mice, were studied. Histological slides of the Purkinje cell layer were prepared from each group for conventional and electron microscopic analysis.

Results: Consistent with previous validation studies, a significant reduction (p<0.05) of Purkinje cell density was observed in F066 mice at five (14.82±2.61) and 12 (13.9±0.58) months of age relative to the control group (23.77±0.46). Similarly, ultrastructural alterations consisting of the loss of mitochondrial cristae, dilation of the rough endoplasmic reticulum and Golgi complex were observed in all three groups of transgenic animals.

Conclusions: Transgenic expression of polyQ-expanded ataxin-2 in the F066 model is associated with progressive degeneration and Purkinje cells ultrastructural damage. Consequently, these results suggest that polyglutane-expanded ataxin-2 could exert its neurotoxic effect through functional alterations of the endoplasmic reticulum, Golgi complex, and mitochondria.

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Author Biography

Dany Amauris Cuello Almartales, Center for Research and Rehabilitation of Hereditary Ataxias, Department of Molecular Neurobiology. Holguín.

The author declare no conflicts of interest.

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Published

2025-12-21

How to Cite

1.
Cuello Almartales DA, Aguiar Santiago J, Fernández Masso JR, Falcón Cama V, Almaguer Mederos LE, Velázquez-Pérez LC. Purkinje cell loss associated with specific ultrastructural alterations in a mouse model with transgenic expression of mutated ataxin-2. Rev haban cienc méd [Internet]. 2025 Dec. 21 [cited 2026 Jan. 20];24:e5451. Available from: https://revhabanera.sld.cu/index.php/rhab/article/view/5451

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Volume 24 (2025): continuous publication

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Biomedical Basic Sciences

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