Glial monocarboxylate transporters (MCTs) pathway in neurodegeneration.

In my postdoctoral research, I found that monocarboxylate transporter 1 (MCT-1) was expressed predominantly in oligodendroglia and a subset of neurons in vivo. Further study indicated that MCT-1 protein was present in the myelin sheath. Deficient MCT-1 expression in MCT-1 heterozygote knockout mice induced significant axonopathy and gliosis. This finding was the first experimental evidence of energy coupling between the axon and its ensheathing myelin, adding a role for myelin as an energy supplier for the axon. Interestingly, MCT-1 expression is significantly reduced in both ALS patients and at the disease end stage in Cu/Zn superoxide dismutase 1 mutant mice, a mouse model of ALS, indicating that MCT-1 is strongly associated with ALS pathogenesis. MCT-1’s role in establishing and maintaining metabolic coupling between the axon and myelin at each developmental stage is critical information yet to be elucidated. Since homozygous null MCT-1 mice are embryonically lethal, I have constructed conditional MCT-1 Knockout mice via Cre/LoxP technology. I have analyzed a PLP-CreERT x MCT-1 (LoxP/LoxP) –, and MOGi-Cre x MCT-1 (LoxP/LoxP)- double transgenic mouse lines to understand in detail role of oligodendroglial MCT-1 in neurodegeneration.