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Expression of Nampt in Hippocampal and Cortical Excitatory Neurons Is Critical for Cognitive Function.
- Source :
-
Journal of Neuroscience . 4/23/2014, Vol. 34 Issue 17, p5800-5815. 16p. - Publication Year :
- 2014
-
Abstract
- 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. NAD+ can be synthesized from several different precursors, among which nicotinamide is the substrate predominantly used in mammals. The rate-limiting step in the NAD+ biosynthetic pathway from nicotinamide is performed by nicotinamide phosphoribosyltransferase (Nampt). Here, we tested the hypothesis that neurons use intracellular Nampt-mediated NAD+ biosynthesis by generating and evaluating mice lacking Nampt in forebrain excitatory neurons (CaMKIIαNampt-/- mice). CaMKIIαNampt-/- mice showed hippocampal and cortical atrophy, astrogliosis, microgliosis, and abnormal CA1 dendritic morphology by 2-3 months of age. Importantly, these histological changes occurred with altered intrahippocampal connectivity and abnormal behavior; including hyperactivity, some defects in motor skills, memory impairment, and reduced anxiety, but in the absence of impaired sensory processes or long-term potentiation of the Schaffer collateral pathway. These results clearly demonstrate that forebrain excitatory neurons mainly use intracellular Nampt-mediated NAD+ biosynthesis to mediate their survival and function. Studying this particular NAD+ biosynthetic pathway in these neurons provides critical insight into their vulnerability to pathophysiological stimuli and the development of therapeutic and preventive interventions for their preservation. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 02706474
- Volume :
- 34
- Issue :
- 17
- Database :
- Academic Search Index
- Journal :
- Journal of Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 95736634
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.4730-13.2014