Kert Mätlik

Background: Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder caused by an abnormally long polyglutamine‐encoding CAG repeat in the ATXN3 gene. Objectives: We aimed to determine whether somatic expansion of the mutant ATXN3 ( mATXN3 ) CAG repeat is present in the output cell of the cerebellar cortex, the Purkinje cell (PC), in individuals affected with SCA3. Methods: We combined sorting of cell nuclei from post‐mortem brain tissue, transcriptome analysis‐based confirmation of sample purity, and high‐depth sequencing of ATXN3 exon 10 amplicons to analyze the stability of mATXN3 CAG repeat in PCs in individuals with SCA3. Results: We demonstrated that the expansion of mATXN3 CAG repeat in PCs is minimal, comparable with cerebellar granule neurons, and the repeat is more stable in PCs compared with striatal medium spiny neurons. Conclusion: The modest somatic expansion of the mATXN3 CAG repeat observed in PCs is likely not responsible for their loss in individuals with SCA3. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Delayed delivery of MANF to rat brain after ischemic stroke promotes functional recovery and recruits phagocytic immune cells.

Ischemic stroke is the leading cause of disability, and effective therapeutic strategies are needed to promote complete recovery. Neuroinflammation plays a significant role in stroke pathophysiology, and there is limited understanding of how it affects recovery. The aim of this study was to characterize the spatiotemporal expression profile of microglial activation and whether dampening microglial/macrophage activation post-stroke facilitates the recovery. For dampening microglial/macrophage activation, we chose intranasal administration of naloxone, a drug that is already in clinical use for opioid overdose and is known to decrease microglia/macrophage activation. We characterized the temporal progression of microglia/macrophage activation following cortical ischemic injury in rat and found the peak activation in cortex 7 d post-stroke. Unexpectedly, there was a chronic expression of phagocytic cells in the thalamus associated with neuronal loss. (+)-Naloxone, an enantiomer that reduces microglial activation without antagonizing opioid receptors, was administered intranasally starting 1 d post-stroke and continuing for 7 d. (+)-Naloxone treatment decreased microglia/macrophage activation in the striatum and thalamus, promoted behavioral recovery during the 14-d monitoring period, and reduced neuronal death in the lesioned cortex and ipsilateral thalamus. Our results are the first to show that post-stroke intranasal (+)-naloxone administration promotes short-term functional recovery and reduces microglia/macrophage activation. Therefore, (+)-naloxone is a promising drug for the treatment of ischemic stroke, and further studies should be conducted.