MAPK8 and Hyperglycemia: This hypothesis is also supported by the results showing cellular stress by increased JNK phosphorylation in T2D rats already at 3 months of age (when hyperglycaemia starts rising [24]) suggesting that the T2D-iduced brain pathology begins at early stages although it does not lead to neuronal loss and apoptosis, at least until the rats are middle-aged (13-months-old).