Hypoxia-ischemia and sexual dimorphism: modeling mitochondrial dysfunction using brain organoids

Abstract Hypoxic–ischemic encephalopathy (HIE) is a leading cause of neurodevelopmental morbidities in full-term infants. There is strong evidence of sexual differences in hypoxic-ischemic (HI) injury where male neonates are at higher risk as they are subject to more pronounced neurological deficits...

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Bibliographic Details
Main Authors: Romane Gaston-Breton, Clémence Disdier, Henrik Hagberg, Aloïse Mabondzo
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Cell & Bioscience
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Online Access:https://doi.org/10.1186/s13578-025-01402-0
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Summary:Abstract Hypoxic–ischemic encephalopathy (HIE) is a leading cause of neurodevelopmental morbidities in full-term infants. There is strong evidence of sexual differences in hypoxic-ischemic (HI) injury where male neonates are at higher risk as they are subject to more pronounced neurological deficits and death than females. The cellular and molecular mechanisms underlying these sexual discrepancies in HI injury are poorly understood. Mitochondrial dysregulation has been increasingly explored in brain diseases and represents a major target during HI events. In this review, we discuss (1) different mitochondrial functions in the central nervous system (2), mitochondrial dysregulation in the context of HI injury (3), sex-dependent mitochondrial pathways in HIE and (4) modeling of mitochondrial dysfunction using human brain organoids. Gaining insight into these novel aspects of mitochondrial function will offer valuable understanding of brain development and neurological disorders such as HI injury, paving the way for the discovery and creation of new treatment approaches.
ISSN:2045-3701