Chunk #26 — Potential Biological Mechanism of Hippocampal Sensitivity to AUDs: Impact of Altered GluN and GABAR Signaling in the Hippocampus on Adult Neurogenesis — Regulation of Neurogenesis by GluNs
Glutamatergic signaling via GluNs is of critical importance in regulating neural stem cells in the hippocampus, particularly in the withdrawal/abstinence period in alcohol-dependent subjects. Under basal conditions, some stages of immature neural progenitors (proliferating and differentiating cells) in the hippocampus express GluNs (158). When coupled with the evidence that GluN-dependent long-term potentiation in the DG can increase progenitor proliferation (159, 160) and survival (159), these findings imply that regulation of hippocampal neurogenesis is sensitive to GluN stimulation on newly born granule cells. Alcohol’s long-term actions via GluNs would, therefore, affect proliferation, survival, and function of the newly born neurons in a dynamic manner which would change over the course of abstinence from alcohol. Alcohol, as described previously, has the consequence of maintaining GluNs at the synapse, effectively impairing cycling of receptors back into the cell for degradation or reuse. Therefore, the role of alcohol on hippocampal neurogenesis would be mediated by either GluN dysregulation, GABA-ergic dysregulation, or a balance of both.
