Functional imaging and neurochemistry identify in vivo neuroprotection mechanisms counteracting excitotoxicity and neurovascular changes in the hippocampus and visual cortex of obese and type 2 diabetic animal models.

Functional MRI (fMRI) with 1 H-MRS were combined on the hippocampus and visual cortex of animal models of obesity (high-fat diet, HFD) and type 2 diabetes (T2D) to identify the mechanisms involved and the temporal evolution of neurometabolic changes in these disorders that could serve as potentially reliable clinical biomarkers. HFD rats presented elevated levels of N-acetylaspartylglutamate (NAAG) (p=0.0365 vs standard diet, SD) and glutathione (GSH) (p=0.0494 vs SD) in the hippocampus. NAAG and GSH levels in this structure proved to be correlated (r = 0.4652, p = 0.0336). This mechanism was not observed in diabetic rats. Combining MRS and fMRI-evaluated blood-oxygen-level-dependent (BOLD) response, elevated taurine (p=0.0326 vs HFD) and GABA type A receptor (GABA A R) (p=0.0211 vs SD and p=0.0153 vs HFD) were observed in the visual cortex of only diabetic rats, counteracting elevated BOLD and suggesting an adaptative mechanism against hyperexcitability observed in the primary visual cortex (V1) (p = 0.0226 vs SD). BOLD amplitude was correlated with the glutamate levels (r=0.4491; p=0.0316). Therefore, here we found evidence for several biological dichotomies regarding excitotoxicity and neuroprotection in different brain regions, identifying putative markers of their different susceptibility and response to the metabolic and vascular insults of obesity and diabetes.