Figure 7.

Schematic model of the possible mechanisms of BDNF/TrkB/HIF-1α involvement in maintaining brain glucose metabolism in P301S mice. Chronic LA treatment induces increased BDNF expression level in neurons and astrocytes in P301S mice brain, then BDNF binding to TrkB-FL induces the activation of TrkB-FL (autophosphorylation of tyrosine sites), BDNF and p-TrkB-FL complex translocate from the cellular membrane through forming endosomes. The complex upregulates HIF-1α protein level and contributes to HIF-1α nucleus translocation, inducing the downstream target genes expression, such as GLUT3, GLUT4, and HO-1, VEGF. The increased glucose transporters and vascular endothelium reinstate glucose metabolism in P301S mice. Also, LA administration upregulates PGC-1α expression and promotes the stabilization of HIF-1α protein level, couple with HIF-1α to induce the downstream target genes.