Expression of Nampt in Hippocampal and Cortical Excitatory Neurons Is Critical for Cognitive Function

摘要: Nicotinamide adenine dinucleotide (NAD+) is an enzyme cofactor or cosubstrate in many essential biological pathways. To date, the primary source of neuronal NAD+ has been unclear. can be synthesized from several different precursors, among which nicotinamide substrate predominantly used mammals. The rate-limiting step biosynthetic pathway performed by phosphoribosyltransferase (Nampt). Here, we tested hypothesis that neurons use intracellular Nampt-mediated biosynthesis generating and evaluating mice lacking Nampt forebrain excitatory (CaMKIIαNampt−/− mice). CaMKIIαNampt−/− showed hippocampal cortical atrophy, astrogliosis, microgliosis, abnormal CA1 dendritic morphology 2–3 months age. Importantly, these histological changes occurred with altered intrahippocampal connectivity behavior; including hyperactivity, some defects motor skills, memory impairment, reduced anxiety, but absence impaired sensory processes long-term potentiation Schaffer collateral pathway. These results clearly demonstrate mainly to mediate their survival function. Studying this particular provides critical insight into vulnerability pathophysiological stimuli development therapeutic preventive interventions for preservation.