Journal
JOURNAL OF PHYSIOLOGICAL SCIENCES
Volume 68, Issue 1, Pages 69-75Publisher
SPRINGER JAPAN KK
DOI: 10.1007/s12576-016-0508-6
Keywords
Astrocyte-neuron lactate shuttle; Brain glycogen; Hippocampus; Monocarboxylate transporter; Type 2 diabetes mellitus
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Funding
- Japan Society for the Promotion of Science [15H01828, 23650384]
- Global Initiative for Sports Neuroscience (GISN): For Development of Exercise Prescription Enhancing Cognitive Functions
- special funds for Education and Research of the Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- Grants-in-Aid for Scientific Research [16H06405] Funding Source: KAKEN
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Astrocyte-neuron lactate shuttle (ANLS) is a pathway that supplies glycogen-derived lactate to active neurons via monocarboxylate transporter 2 (MCT2), and is important for maintaining brain functions. Our study revealed alterations of ANLS with hippocampal hyper-glycogen levels and downregulated MCT2 protein levels underlying hippocampal dysfunctions as a complication in type 2 diabetic (T2DM) animals. Since T2DM rats exhibit brain dysfunctions involving several brain regions, we examined whether there might also be T2DM effects on ANLS's disturbances in other brain loci. OLETF rats exhibited significantly higher glycogen levels in the hippocampus, hypothalamus, and cerebral cortex than did LETO rats. MCT2 protein levels in OLETF rats decreased significantly in the hippocampus and hypothalamus compared to their controls, but a significant correlation with glycogen levels was only observed in the hippocampus. This suggests that the hippocampus may be more vulnerable to T2DM compared to other brain regions in the context of ANLS disruption.
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