Department of Molecular Physiology and Neurobiology, University of Wroclaw, Sienkiewicza 21, Wroclaw, 50-335, Poland.
Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, Martinsried, 82152, Germany.
Glia. 2018 Jul;66(7):1481-1495. doi: 10.1002/glia.23319. Epub 2018 Mar 1.
Lactate derived from astrocytic glycogen has been shown to support memory formation in hippocampi of young animals, inhibiting it in old animals. Here we show, using quantitative mass spectrometry-based proteomics, immunofluorescence, and qPCR that aging is associated with an increase of glycogen metabolism enzymes concentration and shift in their localization from astrocytes to neurons. These changes are accompanied with reorganization of hippocampal energy metabolism which is manifested by elevated capacity of aging neurons to oxidize glucose in glycolysis and mitochondria, and decreased ability for fatty acids utilization. Our observations suggest that astrocyte-to-neuron lactate shuttle may operate in young hippocampi, however, during aging neurons become independent on astrocytic lactate and the metabolic crosstalk between the brain's cells is disrupted.
已有研究表明，星形胶质细胞糖原衍生的乳酸能够支持年轻动物海马体中的记忆形成，而抑制老年动物海马体中的记忆形成。在这里，我们使用基于定量质谱的蛋白质组学、免疫荧光和 qPCR 方法表明，衰老与糖原代谢酶浓度的增加以及其从星形胶质细胞向神经元的定位转变有关。这些变化伴随着海马体能量代谢的重新组织，表现为衰老神经元在糖酵解和线粒体中氧化葡萄糖的能力提高，以及利用脂肪酸的能力降低。我们的观察表明，星形胶质细胞到神经元的乳酸穿梭可能在年轻的海马体中起作用，然而，随着衰老的发生，神经元变得不依赖于星形胶质细胞的乳酸，大脑细胞之间的代谢串扰被打破。
