The Contribution of Adult Hippocampal Neurogenesis to the Progression of Psychiatric Disorders

Abstract

New neurons are continuously formed in the adult hippocampus of the human, nonhuman primate, and rodent throughout life though rates of neurogenesis precipitously decline with age to near zero levels at the end of the natural life span. Since its discovery in the 1960s, a large number of studies have documented numerous environmental and genetic factors which regulate adult neurogenesis. Chief among the positive regulators of neurogenesis are exercise and antidepressant drugs. Chief among the negative regulators of neurogenesis besides age are stress and inflammation. To the extent that many psychiatric disorders are comorbid with or causally related to stress and inflammation, decreased neurogenesis could be a partial contributor to the pathophysiology of the disorders. However, the functional significance of new neurons in behavior has yet to be established and is currently a hotly debated topic. Therefore, it is not clear whether changes in neurogenesis that occur alongside psychiatric illnesses are a cause or a consequence of the mediating factors such as stress, drug abuse, and inflammation, which are complexly involved in the disorders. It will be important moving forward to use modern technologies capable of instantaneously inactivating cohorts of new neurons to test their functional significance in behavior and the etiology of mental illnesses.

Enhanced Susceptibility to Chemoconvulsant-Induced Seizures in Ganglioside GM3 Synthase Knockout Mice

“…After extensive studies based on physiological and pathophysiological stimuli, adult hippocampal neurogenesis appears to be necessary and beneficial (Kang et al., 2016; Baptista & Andrade, 2018). In contrast, epileptic seizures led to aberrant hippocampal neurogenesis, including increased proliferation of neural progenitors, production of ectopic granule cells, and persistence of hilar basal dendrites on adult-generated granule neurons (Parent et al., 1997; Kohman & Rhodes, 2017). On the other hand, hippocampal neurogenesis also plays an important role in the development of chronic seizures (Danzer, 2019).…”

Brain microstructural changes in mice persist in adulthood and are modulated by the palmitoyl acyltransferase ZDHHC7

“…A preceding overproduction of axons and synapses is typically followed by rapid pruning (Agoglia et al, 2017; Rakic et al, 1994; Schneider, 2013) and enhanced myelination during adolescence (Paus et al, 2008), which leads to a decline of grey matter (Agoglia et al, 2017). Only few studies indicate that in adulthood, neuronal modelling through myelination and pruning continues (Forrest et al, 2018; Kohman & Rhodes, 2017). As well, neurogenesis continues but declines with age (Kohman & Rhodes, 2017) and could be modified by myelination.…”

The Analysis of Oxidative Stress Markers May Increase the Accuracy of the Differential Diagnosis of Alzheimer’s Disease with and without Depression

“… 20 In addition, MDD pathophysiology is associated with an inflammatory process due to microglial activation, increased cytokine release and increased oxidative stress, astrocyte atrophy and changes in glutamatergic regulation, which can lead to local damage. 21 The activated microglial initiates the fission of precursor forms of interleukin-1β (IL-1β) into its active form. 22 , 23 Exacerbation of the inflammatory process can result in a significant increase in the production and expression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and IL-1β, as well as reactive oxygen species (ROS) and nitric oxide, contributing to neurodegenerative processes associated with psychiatric disorders.…”