Lundquist Adam J, Gallagher Tyler J, Petzinger Giselle M, Jakowec Michael W
Department of Neurology, University of Southern California, Los Angeles, CA, USA.
Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, CA, USA.
J Neurosci Res. 2021 May;99(5):1433-1447. doi: 10.1002/jnr.24804. Epub 2021 Feb 25.
l-Lactate is an energetic and signaling molecule that may be produced through astrocyte-specific aerobic glycolysis and is elevated in striatal muscle during intensive exercise. l-Lactate has been shown to promote neurotrophic gene expression through astrocytes within the hippocampus, however, its role in neuroplasticity within the striatum remains unknown. This study sought to investigate the role of peripheral sources of l-lactate in promoting astrocyte-specific gene expression and morphology as well as its role in neuroplasticity within the striatum of healthy animals. Using in vitro primary astrocyte cell culture, administration of l-lactate increased the expression of the neurotrophic factors Bdnf, Gdnf, Cntf, and the immediate early gene cFos. l-Lactate's promotion of neurotrophic factor expression was mediated through the lactate receptor HCAR1 since application of the HCAR1 agonist 3,5-DHBA also increased expression of Bdnf in primary astrocytes. Similar to our previous report demonstrating exercise-induced changes in astrocytic structure within the striatum, l-lactate administration to healthy mice led to increased astrocyte morphological complexity as well as astrocyte-specific neurotrophic expression within the striatum. Our study failed to demonstrate an effect of peripheral l-lactate on synaptogenesis or motor behavior. Insufficient levels and/or inadequate delivery of l-lactate through regional cerebral blood flow within the striatum may account for the lack of these benefits. Taken together, these novel findings suggest a potential framework that links peripheral l-lactate production within muscle and intensive exercise with neuroplasticity of specific brain regions through astrocytic function.
左旋乳酸是一种能量和信号分子，可通过星形胶质细胞特异性有氧糖酵解产生，在剧烈运动时纹状肌中含量会升高。已有研究表明，左旋乳酸可通过海马体中的星形胶质细胞促进神经营养基因表达，然而，其在纹状体神经可塑性中的作用尚不清楚。本研究旨在探讨外周来源的左旋乳酸在促进星形胶质细胞特异性基因表达和形态方面的作用，以及其在健康动物纹状体神经可塑性中的作用。通过体外原代星形胶质细胞培养，给予左旋乳酸可增加神经营养因子Bdnf、Gdnf、Cntf以及即刻早期基因cFos的表达。左旋乳酸对神经营养因子表达的促进作用是通过乳酸受体HCAR1介导的，因为应用HCAR1激动剂3,5-二羟基苯甲酸也可增加原代星形胶质细胞中Bdnf的表达。与我们之前报道的运动诱导纹状体内星形胶质细胞结构变化相似，给健康小鼠注射左旋乳酸可导致纹状体内星形胶质细胞形态复杂性增加以及星形胶质细胞特异性神经营养表达增加。我们的研究未能证明外周左旋乳酸对突触形成或运动行为有影响。纹状体内通过局部脑血流输送的左旋乳酸水平不足和/或输送不充分可能是缺乏这些益处的原因。综上所述，这些新发现提出了一个潜在的框架，将肌肉内外周左旋乳酸的产生和剧烈运动与特定脑区通过星形胶质细胞功能实现的神经可塑性联系起来。
