Uehara Takashi, Sumiyoshi Tomiki, Itoh Hiroko, Kurata Koichi
Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan.
Pharmacol Biochem Behav. 2008 Aug;90(2):273-81. doi: 10.1016/j.pbb.2008.04.001. Epub 2008 Apr 8.
Recent studies have found that lactate metabolism plays a significant role in energy supply during acute neural activation in the brain. We will review evidence from microdialysis studies for a relationship between neurotransmitters and lactate production, as revealed in studies of the effects of psychotropic drugs on stress-induced enhancement of extracellular lactate concentrations. Glutamate enhances stress-induced lactate production via activation of N-methyl-D-asparate receptors, and is affected by uptake of glutamate through glutamate transporters. Findings from microdialysis studies suggest that major neurotransmitters, including norepinephrine, dopamine, serotonin, and GABA (via benzodiazepine-receptors) affect lactate production, depending on brain areas, especially during stress. Among these neurotransmitters, glutamate may principally contribute to the regulation of lactate production, with other neurotransmitter systems affecting the extracellular lactate levels in a glutamate-mediated manner. The role for anaerobic metabolism in the supply of energy, as represented by lactate dynamics, deserves further clarification. Monitoring with intracerebral microdialysis is a reliable method for this purpose. Research into this area is likely to provide a novel insight into the mode of action of psychotropic drugs, and the pathophysiology of some of the stress-related mental disorders as well.
最近的研究发现,乳酸代谢在大脑急性神经激活过程中的能量供应中起着重要作用。我们将回顾微透析研究中的证据,以探讨神经递质与乳酸生成之间的关系,这在精神药物对应激诱导的细胞外乳酸浓度升高的影响研究中有所揭示。谷氨酸通过激活N-甲基-D-天冬氨酸受体增强应激诱导的乳酸生成,并受谷氨酸转运体对谷氨酸摄取的影响。微透析研究结果表明,包括去甲肾上腺素、多巴胺、5-羟色胺和γ-氨基丁酸(通过苯二氮䓬受体)在内的主要神经递质会影响乳酸生成,这取决于脑区,尤其是在应激期间。在这些神经递质中,谷氨酸可能主要参与乳酸生成的调节,其他神经递质系统则以谷氨酸介导的方式影响细胞外乳酸水平。以乳酸动态为代表的无氧代谢在能量供应中的作用值得进一步阐明。为此,脑内微透析监测是一种可靠的方法。该领域的研究可能会为精神药物的作用模式以及一些与应激相关的精神障碍的病理生理学提供新的见解。