Astrocyte-mediated disruption of ROS homeostasis in Fragile X mouse model

Vandenberg, G. G., Dawson, N. J. , Head, A., Scott, G. R. and Scott, A. L. (2021) Astrocyte-mediated disruption of ROS homeostasis in Fragile X mouse model. Neurochemistry International, 146, 105036. (doi: 10.1016/j.neuint.2021.105036) (PMID:33785420)

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Abstract

Astrocytes, glial cells within the brain, work to protect neurons during high levels of activity by maintaining oxidative homeostasis via regulation of energy supply and antioxidant systems. In recent years, mitochondrial dysfunction has been highlighted as an underlying factor of pathology in many neurological disorders. In animal studies of Fragile X Syndrome (FXS), the leading genetic cause of autism, higher levels of reactive oxygen species, lipid peroxidation, and protein oxidation within the brain indicates that mitochondria function is also altered in FXS. Despite their integral contribution to redox homeostasis within the CNS, the role of astrocytes on the occurrence or progression of neurodevelopmental disorders in this way is rarely considered. This study specifically examines changes to astrocyte mitochondrial function and antioxidant expression that may occur in FXS. Using the Fmr1 knockout (KO) mouse model, mitochondrial respiration and reactive oxygen species (ROS) emission were analyzed in primary cortical astrocytes. While mitochondrial respiration was similar between genotypes, ROS emission was significantly elevated in Fmr1 KO astrocytes. Notably, NADPH-oxidase 2 expression in Fmr1 KO astrocytes was also enhanced but only changes in catalase antioxidant enzyme expression were noted. Characterization of astrocyte factors involved in redox imbalance is invaluable to uncovering potential sources of oxidative stress in neurodevelopmental disorders and more specifically, the intercellular mechanisms that contribute to dysfunction in FXS.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Dawson, Dr Neal
Authors: Vandenberg, G. G., Dawson, N. J., Head, A., Scott, G. R., and Scott, A. L.
Subjects:Q Science > QH Natural history
Q Science > QH Natural history > QH301 Biology
Q Science > QM Human anatomy
Q Science > QP Physiology
Q Science > QR Microbiology
Q Science > QR Microbiology > QR180 Immunology
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:Neurochemistry International
Publisher:Elsevier
ISSN:0197-0186
ISSN (Online):1872-9754
Published Online:27 March 2021

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