Prediabetes and type 2 diabetes implication in central proliferation and neurogenesis

Abstract

Type 2 diabetes (T2D) is an important risk factor for developing dementias, including Alzheimer's disease (AD). Hyperinsulinemia and glucose intolerance, as features of T2D, might increase the neurodegeneration process, synaptic loss and brain atrophy, leading to cognitive impairment observed in AD. Also, adult neurogenesis seems to be impaired in AD models. Therefore, we have studied morphological alterations, cell proliferation and neurogenesis in the central nervous system (CNS) from a classical model of T2D, the db/db mouse, and in a prediabetes insulin-resistant model, obtained after long-term high fat diet (HFD) administration to C57Bl/6 mice. Db/db mice showed an age-dependent cortical and hippocampal atrophy, whereas in HFD mice cortex and hippocampus were preserved. Neurogenesis and cell proliferation were increased in young db/db mice, when compared with control mice, whereas no differences were detected in the prediabetic model. We also detected significant correlations between metabolic parameters and central atrophy, altered proliferation and neurogenesis in the central nervous system. Altogether these data support that glycaemia control in elderly patients, could help to control central alterations and improve dementia prognosis.