Brain insulin resistance impairs hippocampal plasticity

Nutrient-related signals have been demonstrated to influence brain development and cognitive functions. In particular, insulin signaling has been shown to impact on molecular cascades underlying hippocampal plasticity, learning and memory. Alteration of brain insulin signaling interferes with the maintenance of neural stem cell niche and neuronal activity in the hippocampus. Brain insulin resistance is also emerging as key factor causing the cognitive impairment observed in metabolic and neurodegenerative diseases. Here, we review the molecular mechanisms involved in the insulin modulation of both adult neurogenesis and synaptic activity in the hippocampus. We also summarize the effects of altered insulin sensitivity on hippocampal plasticity. Finally, we reassume the experimental and epidemiological evidence highlighting the critical role of brain insulin resistance at the crossroad between type 2 diabetes and Alzheimer's disease.