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Vandenberg 2022 Am J Physiol Cell Physiol

From Bioblast
Publications in the MiPMap
Vandenberg GG, Thotakura A, Scott AL (2022) Mitochondrial bioenergetics of astrocytes in Fragile X syndrome: new perspectives on culture conditions and sex effects. Am J Physiol Cell Physiol 322:C125-35.

Β» PMID: 34817267 Open Access

Vandenberg GG, Thotakura A, Scott AL (2022) Am J Physiol Cell Physiol

Abstract: Fragile X syndrome (FXS) is a genetic disorder that is characterized by a range of cognitive and behavioral deficits, including mild-moderate intellectual disability. The disease is characterized by an X-linked mutation of the Fmr1 gene, which causes silencing of the gene coding for fragile X mental retardation protein (FMRP), a translational regulator integral for neurodevelopment. Mitochondrial dysfunction has been recently associated with FXS, with reports of increases in oxidative stress markers, reactive oxygen species, and lipid peroxidation being present in the brain tissue. Astrocytes, a prominent glial cell within the central nervous system (CNS), play a large role in regulating oxidative homeostasis within the developing brain and dysregulation of astrocyte redox balance in FXS, which may contribute to oxidative stress. Astrocyte function and mitochondrial bioenergetics are significantly influenced by oxygen availability and circulating sex hormones; yet, these parameters are rarely considered during in vitro experimentation. Given that the brain normally develops in a range of hypoxic conditions and FXS is a sex-linked genetic disorder, we investigated how different oxygen levels (normoxic vs. hypoxic) and biological sex affected mitochondrial bioenergetics of astrocytes in FXS. Our results demonstrate that both mitochondrial respiration capacity and reactive oxygen species emission are altered with Fmr1 deletion in astrocytes and these changes were dependent upon both sexual dimorphism and oxygen availability.

β€’ Bioblast editor: Gnaiger E β€’ O2k-Network Lab: CA Hamilton Scott GR

Labels: MiParea: Respiration, Genetic knockout;overexpression, Gender  Pathology: Neurodegenerative  Stress:Oxidative stress;RONS, Hypoxia  Organism: Mouse  Tissue;cell: Nervous system  Preparation: Permeabilized cells 

Regulation: Oxygen kinetics  Coupling state: LEAK, OXPHOS  Pathway: N, S, CIV, NS, ROX  HRR: Oxygraph-2k, O2k-Fluorometer