Campos Kiara França, Vizuete Adriana Fernanda Kuckartz, Machado Diorlon Nunes, Carvalho Andrey Vinicios Soares, Durán-Carabali Luz Elena, Netto Carlos Alexandre
Graduate Program in Biological Sciences: Physiology, Instituto de Ciências Básicas da Saúde, Universidade Federal Do Rio Grande Do Sul (UFRGS), Porto Alegre, Brazil.
Graduate Program in Biological Sciences: Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal Do Rio Grande Do Sul (UFRGS), Porto Alegre, Brazil.
Mol Neurobiol. 2025 Jun 11. doi: 10.1007/s12035-025-05118-7.
The mammalian brain uses several energy substrates during development, such as lactate, ketone bodies, and glucose, to avoid energy imbalances that may lead to cellular dysfunction. Sex differences in brain function are well-documented, with males being more susceptible to neurodevelopmental disturbances than females; however, the underlying reason for this vulnerability is not fully elucidated. Present study aimed to investigate sex differences in energy metabolism at different postnatal ages. Wistar rats of both sexes were evaluated on postnatal days (PND) 1, 7, 14, 21, and 60. Biochemical parameters included the immunocontent of ketone bodies (KB) and glucose transporters, glucose uptake in the hippocampus, and the levels of lactate, glucose, and beta-hydroxybutyrate (BOHB) in serum and cerebrospinal fluid. Moreover, beta-hydroxybutyrate dehydrogenase (BHD) activity was evaluated in the liver and the hippocampus. Immunofluorescence staining was performed to label the distribution of monocarboxylate transporters (MCTs) in the hippocampus and the corpus callosum. Serum lactate and BOHB levels were higher at PND1 than at other ages. Animals at PND14 predominantly utilize BOHB as a substrate, followed by a transition phase to glucose during weaning. Female rats exhibited an increase in the immunocontent of MCT2, MCT1, MCT4, and GLUT1 throughout postnatal development, suggesting a metabolic advantage over males due to greater uptake efficiency of energy substrates. Present findings reveal sex-specific differences in the expression of glucose and MCTs monocarboxylate transporters during postnatal brain development. A deeper understanding of these metabolic differences among healthy individuals may elucidate crucial sex-specific features of in neurological disorders, such as hypoxia-ischemia. This understanding could facilitate the advancement of more precise and targeted therapeutic interventions.
哺乳动物大脑在发育过程中会使用多种能量底物，如乳酸、酮体和葡萄糖，以避免可能导致细胞功能障碍的能量失衡。大脑功能的性别差异已有充分记录，男性比女性更容易受到神经发育障碍的影响；然而，这种易感性的根本原因尚未完全阐明。本研究旨在调查不同出生后年龄的能量代谢性别差异。对雌雄Wistar大鼠在出生后第1、7、14、21和60天进行评估。生化参数包括酮体（KB）和葡萄糖转运蛋白的免疫含量、海马体中的葡萄糖摄取以及血清和脑脊液中乳酸、葡萄糖和β-羟基丁酸（BOHB）的水平。此外，还评估了肝脏和海马体中的β-羟基丁酸脱氢酶（BHD）活性。进行免疫荧光染色以标记海马体和胼胝体中一元羧酸转运蛋白（MCTs）的分布。出生后第1天血清乳酸和BOHB水平高于其他年龄。出生后第14天的动物主要利用BOHB作为底物，随后在断奶期间过渡到葡萄糖。雌性大鼠在整个出生后发育过程中MCT2、MCT1、MCT4和GLUT1的免疫含量增加，这表明由于能量底物的摄取效率更高，雌性大鼠比雄性大鼠具有代谢优势。目前的研究结果揭示了出生后大脑发育过程中葡萄糖和MCTs一元羧酸转运蛋白表达的性别特异性差异。深入了解健康个体之间的这些代谢差异可能有助于阐明神经系统疾病（如缺氧缺血）中关键的性别特异性特征。这种理解有助于推进更精确、更有针对性的治疗干预措施。
