Functional Role of Adult Hippocampal Neurogenesis as a Therapeutic Strategy for Mental Disorders

Abstract

Adult neurogenesis, the process of generating new neurons from neural stem cells, plays significant roles in synaptic plasticity, memory, and mood regulation. In the mammalian brain, it continues to occur well into adulthood in discrete regions, namely, the hippocampus and olfactory bulb. During the past decade, significant progress has been made in understanding the mechanisms regulating adult hippocampal neurogenesis and its role in the etiology of mental disorders. In addition, adult hippocampal neurogenesis is highly correlated with the remission of the antidepressant effect. In this paper, we discuss three major psychiatric disorders, depression, schizophrenia, and drug addiction, in light of preclinical evidence used in establishing the neurobiological significance of adult neurogenesis. We interpret the significance of these results and pose questions that remain unanswered. Potential treatments which include electroconvulsive therapy, deep brain stimulation, chemical antidepressants, and exercise therapy are discussed. While consensus lacks on specific mechanisms, we highlight evidence which indicates that these treatments may function via an increase in neural progenitor proliferation and changes to the hippocampal circuitry. Establishing a significant role of adult neurogenesis in the pathogenicity of psychiatric disorders may hold the key to potential strategies toward effective treatment.

How to make a hippocampal dentate gyrus granule neuron

“…As cognitive dysfunction associated with aberrant hippocampal neurogenesis has been implicated in CNS disorders, generation of DG granule neurons from patient cells may offer a unique opportunity for disease modeling and drug discovery (Jun et al, 2012). Although translation of these findings to a clinical setting is still far away, it is still possible to gain insight into the physiological processes that manifest in certain neuropathological diseases, perhaps hinting at possible targets for pharmaceutical intervention.…”

“…Aberrant hippocampal neurogenesis is implicated in a number of neurological pathologies, and interventions aimed at regulating neurogenesis have been proposed as potential therapeutic strategies (Jun et al, 2012). Epileptic seizures have been shown to affect neurogenesis and the emergence of abnormal hilar basal dendrites in newborn granule neurons.…”

A natural diarylheptanoid promotes neuronal differentiation via activating ERK and PI3K-Akt dependent pathways

“…Adult neurogenesis plays crucial roles in learning and memory and mood control, and has been shown as an important therapeutic target for neurodegenerative diseases and mental disorders (Sailor et al, 2006;Jun et al, 2012;Schoenfeld and Cameron, 2014). Importantly, Cpd 1 promoted the differentiation and maturation of adult-born neurons in the dentate gyrus.…”

“…Dentate neurogenesis is crucial to maintain homeostatic plasticity of hippocampal circuitry, and its disruption is tightly linked with a number of neurological diseases, including Alzheimer's disease and depression (Drew et al, 2013). Hence, developing therapeutic approaches that target on neuronal differentiation and adult neurogenesis will be greatly beneficial for the regeneration of neurons or reconstruction of synaptic networks in neurological diseases such as neurodegenerative diseases, brain injuries and mood disorders (Sailor et al, 2006;Jun et al, 2012;Kim and Jin, 2012).…”

Connexin and pannexin signaling pathways, an architectural blueprint for CNS physiology and pathology?

“…Hence, Panx1 does play a channel-dependent as well as channel-independent role in postnatal/adult neurogenesis. The insight that both Cxs and Panxs can contribute to adult neurogenesis might be of interest for the treatment of neurodegenerative and mental disorders [188,189].…”