PPARγ-mediated advanced glycation end products regulation of neural stem cells

Hyperglycemia is accompanied by an accelerated rate of advanced glycation end products (AGEs) formation, which is found to be associated with the pathogenesis of diabetic cognitive deficit, including Alzheimer's disease (AD). Peroxisome proliferator-activated receptor γ (PPARγ) plays an important role in controlling the proliferation of neural stem cells (NSCs) and their neuronal differentiation. We investigate the hypothesis that PPARγ could mediate AGEs-related regulation of NSCs, by which AGEs possibly fulfill important roles in diabetic-related cognitive impairment. We found that AGEs down-regulated the proliferation and neurogenic differentiation of NSCs, and protein level of PPARγ. PPARγ agonist reversed the proliferation through the aid of AGE-BSA, with the exclusion of the neuronal differentiation of the NSCs which were also downregulated by AGE-BSA. These findings extend our understanding of the central role of PPARγ in AGEs-related neurogenesis impairment, which probably increased risks of cognitive deficits or AD in diabetic patients.