HORMONE-DEPENDENT MITOCHONDRIAL LIPID METABOLISM DURING BRAIN DEVELOPMENT

ASTIZ MARIANA; ACAZ-FONSECA, ESTEFANIA; LOPEZ-RODRIGUEZ, ANA BELEN; ORTIZ-RODRIGUEZ, ANA; GARCIA-SEGURA, LUIS M

Copenhagen

Congreso; 10th FENS Forum of Neuroscience; 2016

FENS (Federation of European Neurosciences Societies)

During perinatal period, testosterone (T) released in males, plays a role in sexual dimorphic brain development. Mitochondrial metabolism is highly active during this period. We aimed to study the role of T in cardiolipin (CL) metabolism and the underlying mechanism. C57BL/6 offspring were separated by sex at different postnatal days (PND 0-10) to assess T levels in plasma, the expression of enzymes involved in CL de novo synthesis and recycling pathways and CL content and composition in cerebral cortex.A sexual dimorphism was detected in CL fatty acid composition; CL from males contains more unsaturated fatty acids than CL from females at PND 0-3. This difference is at least in part due to T-effect because is prevented by female androgenization just after birth. T also modulates the expression of iPLA2 and TAZ, both involved in the CL recycling pathway, and likely the availability of PUFAs by changing the expression of ∆5 and ∆6 desaturases.It is possible that T modulates mitochondrial function and dynamics. The activity of the mitochondrial electron transport chain complexes (I, II and IV) is similar, but the expression of fission/fusion proteins (Drp-1 and Mfn-2) is different among sexes.As there are sequences of estrogen responsive elements in the promoters of these enzymes, we are using cultured astrocytes to identify the mechanisms underlying the role of T in CL metabolism. This sexual dimorphism would be relevant to understand the role of lipids in brain development, and possible long-lasting consequences of an early exposure to any endocrine disruptors.