Marullo, Chiara;
Croci, Laura;
Giupponi, Iris;
Rivoletti, Claudia;
Zuffetti, Sofia;
Bettegazzi, Barbara;
Cremona, Ottavio;
... Codazzi, Franca; + view all
(2025)
Altered Ca²⁺ responses and antioxidant properties in Friedreich's ataxia-like cerebellar astrocytes.
Journal of Cell Science
, 138
(1)
, Article jcs263446. 10.1242/jcs.263446.
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Abstract
Friedreich's ataxia (FRDA) is a neurodegenerative disorder characterized by severe neurological signs, affecting the peripheral and central nervous system, caused by reduced frataxin protein (FXN) levels. While several studies highlight cellular dysfunctions in neurons, there is limited information on the effects of FXN depletion in astrocytes and on the potential non-cell autonomous mechanisms affecting neurons in FRDA. In this study, we generated a model of FRDA cerebellar astrocytes to unveil phenotypic alterations that might contribute to cerebellar atrophy. We treated primary cerebellar astrocytes with an RNA interference-based approach, to achieve a reduction of FXN comparable to that observed in patients. These FRDA-like astrocytes display some typical features of the disease, such as an increase of oxidative stress and a depletion of glutathione content. Moreover, FRDA-like astrocytes exhibit decreased calcium responses to purinergic stimuli. Our findings shed light on cellular changes caused by FXN downregulation in cerebellar astrocytes, likely impairing their complex interaction with neurons. The potentially impaired ability to provide neuronal cells with glutathione or to release neuromodulators in a calcium-dependent manner could affect neuronal function, contributing to neurodegeneration.
| Type: | Article |
|---|---|
| Title: | Altered Ca²⁺ responses and antioxidant properties in Friedreich's ataxia-like cerebellar astrocytes |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1242/jcs.263446 |
| Publisher version: | https://doi.org/10.1242/jcs.263446 |
| Language: | English |
| Additional information: | Copyright © 2025. Published by The Company of Biologists. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
| Keywords: | Calcium signalling, Cerebellar astrocytes, Friedreich's ataxia, Mitochondria, Oxidative stress |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10201517 |
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