title: Developmental Sex Differences in the Metabolism of Cardiolipin in Mouse Cerebral Cortex Mitochondria.
abstract: Cardiolipin (CL) is a mitochondrial-specific phospholipid. CL content and acyl chain composition are crucial for energy production. Given that estradiol induces CL synthesis in neurons, we aimed to assess CL metabolism in the cerebral cortex (CC) of male and female mice during early postnatal life, when sex steroids induce sex-dimorphic maturation of the brain. Despite the fact that total amount of CL was similar, its fatty acid composition differed between males and females at birth. In males, CL was more mature (lower saturation ratio) and the expression of the enzymes involved in synthetic and remodeling pathways was higher, compared to females. Importantly, the sex differences found in CL metabolism were due to the testosterone peak that male mice experience perinatally. These changes were associated with a higher expression of UCP-2 and its activators in the CC of males. Overall, our results suggest that the perinatal testosterone surge in male mice regulates CL biosynthesis and remodeling in the CC, inducing a sex-dimorphic fatty acid composition. In male's CC, CL is more susceptible to peroxidation, likely explaining the testosterone-dependent induction of neuroprotective molecules such as UCP-2. These differences may account for the sex-dependent mitochondrial susceptibility after perinatal hypoxia/ischemia.
authors.affiliation: Instituto Cajal-CSIC. Avenida Doctor Arce 37, 28002 Madrid, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Acaz-Fonseca
authors.affiliation: Instituto Cajal-CSIC. Avenida Doctor Arce 37, 28002 Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Ortiz-Rodriguez
authors.affiliation: Instituto Cajal-CSIC. Avenida Doctor Arce 37, 28002 Madrid, Spain.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Lopez-Rodriguez
authors.affiliation: Instituto Cajal-CSIC. Avenida Doctor Arce 37, 28002 Madrid, Spain.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Garcia-Segura
authors.affiliation: Instituto Cajal-CSIC. Avenida Doctor Arce 37, 28002 Madrid, Spain.|Biochemistry Research Institute of La Plata (INIBIOLP), CONICET. 60 and 120, 1900, La Plata, Argentina.
authors.forename: Mariana
authors.initials: M
authors.lastname: Astiz
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002308:Cardiolipins / Q000378:metabolism*; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D012737:Sex Factors; D013739:Testosterone / Q000378:metabolism*; D013997:Time Factors; D000071246:Uncoupling Protein 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D002308:Cardiolipins; D005227:Fatty Acids; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D013739:Testosterone