Laboratory of Protein Chemistry and Biochemistry, Department of Cell Biology, Institute of Biology, University of Brasília, Brasília, DF, 70910-900, Brazil.
Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, 90035-003, Brazil.
Sci Rep. 2021 Jan 28;11(1):2560. doi: 10.1038/s41598-021-82016-7.
Sex differences in the brain of mammals range from neuroarchitecture through cognition to cellular metabolism. The hippocampus, a structure mostly associated with learning and memory, presents high vulnerability to neurodegeneration and aging. Therefore, we explored basal sex-related differences in the proteome of organotypic hippocampal slice culture, a major in vitro model for studying the cellular and molecular mechanisms related to neurodegenerative disorders. Results suggest a greater prevalence of astrocytic metabolism in females and significant neuronal metabolism in males. The preference for glucose use in glycolysis, pentose phosphate pathway and glycogen metabolism in females and high abundance of mitochondrial respiration subunits in males support this idea. An overall upregulation of lipid metabolism was observed in females. Upregulation of proteins responsible for neuronal glutamate and GABA synthesis, along with synaptic associated proteins, were observed in males. In general, the significant spectrum of pathways known to predominate in neurons or astrocytes, together with the well-known neuronal and glial markers observed, revealed sex-specific metabolic differences in the hippocampus. TEM qualitative analysis might indicate a greater presence of mitochondria at CA1 synapses in females. These findings are crucial to a better understanding of how sex chromosomes can influence the physiology of cultured hippocampal slices and allow us to gain insights into distinct responses of males and females on neurological diseases that present a sex-biased incidence.
哺乳动物大脑中的性别差异范围从神经结构到认知再到细胞代谢。海马体是一个主要与学习和记忆相关的结构，对神经退行性变和衰老非常敏感。因此，我们在器官型海马切片培养的蛋白质组中探索了基础的性别相关差异，器官型海马切片培养是研究与神经退行性疾病相关的细胞和分子机制的主要体外模型。结果表明，女性中海马体细胞代谢更为活跃，而男性中神经元代谢更为显著。女性中糖酵解、磷酸戊糖途径和糖原代谢中更倾向于使用葡萄糖，而男性中富含线粒体呼吸亚基，这一结果支持了上述观点。女性的脂质代谢总体上调。男性中观察到与神经元谷氨酸和 GABA 合成以及突触相关蛋白相关的蛋白质上调。总的来说，已知在神经元或星形胶质细胞中占主导地位的显著途径谱，以及观察到的众所周知的神经元和神经胶质标志物，揭示了海马体中的性别特异性代谢差异。TEM 定性分析可能表明女性 CA1 突触中存在更多的线粒体。这些发现对于更好地理解性染色体如何影响培养海马切片的生理学至关重要，并使我们能够深入了解在具有性别偏倚发病率的神经疾病中男性和女性的不同反应。
