Re-evaluating the link between neuropsychiatric disorders and dysregulated adult neurogenesis

Abstract

People diagnosed with neuropsychiatric disorders such as depression, anxiety, addiction or schizophrenia often have dysregulated memory, mood, pattern separation and/or reward processing. These symptoms are indicative of a disrupted function of the dentate gyrus (DG) subregion of the brain, and they improve with treatment and remission. The dysfunction of the DG is accompanied by structural maladaptations, including dysregulation of adult-generated neurons. An increasing number of studies using modern inducible approaches to manipulate new neurons show that the behavioral symptoms in animal models of neuropsychiatric disorders can be produced or exacerbated by the inhibition of DG neurogenesis. Thus, here we posit that the connection between neuropsychiatric disorders and dysregulated DG neurogenesis is beyond correlation or epiphenomenon, and that the regulation of adult-generated DG neurogenesis merits continued and focused attention in the ongoing effort to develop novel treatments for neuropsychiatric disorders.

What is CAR doing in the middle of the adult neurogenic road?

“…Consistent with this, AD is also associated with impaired adult neurogenesis. 14,[29][30][31][32] In hippocampal extracts from AD patients, we detected a significant decrease in CAR expression (on newborn neurons and in axons projecting from the entorhinal cortex, a region particularly affected in AD), suggesting that CAR is affected/involved in disorders where chronic inflammation, impaired adult neurogenesis, and synapse homeostasis are found. 7 Yet, it remains unclear as to why the genetic ablation of CAR expression (early in development) impacted female mice greater than male mice.…”

Whole-Body Exposure to28Si-Radiation Dose-Dependently Disrupts Dentate Gyrus Neurogenesis and Proliferation in the Short Term and New Neuron Survival and Contextual Fear Conditioning in the Long Term

“…This is useful, since the hippocampus varies in function along its longitudinal axis, as in the rodent: the more anterior/dorsal/septal hippocampus is linked to spatial learning and memory, and the more posterior/ventral/temporal hippocampus is linked to emotion and mood regulation (72–78). Because neurogenesis is linked to both spatial memory and mood (65, 78, 79), examination along the septotemporal axis allows insight into DG neurogenesis that may be associated with specific changes in function (80–83). In fact, inducible manipulation of neurogenesis in the anterior compared to posterior DG disrupts spatial versus emotionally-linked hippocampal function, respectively (83).…”

Opiate Analgesics as Negative Modulators of Adult Hippocampal Neurogenesis: Potential Implications in Clinical Practice

“…These findings have important clinical implications since they raise the possibility that cognitive dysfunction and/or mood alteration in the setting of such drug use and/or abuse may, at least in part, be related to alterations in ahNG (Yun et al, 2016). …”