Role of Adult Hippocampal Neurogenesis in Cognition in Physiology and Disease: Pharmacological Targets and Biomarkers

Abstract

Adult hippocampal neurogenesis is a remarkable form of brain structural plasticity by which new functional neurons are generated from adult neural stem cells/precursors. Although the precise role of this process remains elusive, adult hippocampal neurogenesis is important for learning and memory and it is affected in disease conditions associated with cognitive impairment, depression, and anxiety. Immature neurons in the adult brain exhibit an enhanced structural and synaptic plasticity during their maturation representing a unique population of neurons to mediate specific hippocampal function. Compelling preclinical evidence suggests that hippocampal neurogenesis is modulated by a broad range of physiological stimuli which are relevant in cognitive and emotional states. Moreover, multiple pharmacological interventions targeting cognition modulate adult hippocampal neurogenesis. In addition, recent genetic approaches have shown that promoting neurogenesis can positively modulate cognition associated with both physiology and disease. Thus the discovery of signaling pathways that enhance adult neurogenesis may lead to therapeutic strategies for improving memory loss due to aging or disease. This chapter endeavors to review the literature in the field, with particular focus on (1) the role of hippocampal neurogenesis in cognition in physiology and disease; (2) extrinsic and intrinsic signals that modulate hippocampal neurogenesis with a focus on pharmacological targets; and (3) efforts toward novel strategies pharmacologically targeting neurogenesis and identification of biomarkers of human neurogenesis.

Resveratrol promotes hUC-MSCs engraftment and neural repair in a mouse model of Alzheimer’s disease

“…Mesenchymal stem cells have been demonstrated to secret several factors, BDNF, bFGF, CNTF, FGF-2, GDNF, HGF, IGF, NGF, NT-3, VEGF, to regulate the microenvironment in the brain [33]. We explored neurotropic factors, BDNF, NGF, and NT-3, which were known to be important for neurogenesis [34], learning and memory [35]. We found that hUC-MSCs upregulated the expression of BDNF, NGF, and NT-3 in the hippocampus, and the effects were further enhanced when hUC-MSCs was combined with resveratrol, therefore, hippocampal neurogenesis and cognition were enhanced.…”

Glypican-2 levels in cerebrospinal fluid predict the status of adult hippocampal neurogenesis

“…A plethora of animal studies have implicated adult-born hippocampal neurons, which have different physiological properties than mature neurons, in many non-mutually exclusive roles in brain function, such as formation, spatial memory, pattern separation and the regulation of stress and affective states. Furthermore, in animal models of neurodevelopmental disorders, Alzheimer’s disease, stress and depression, alterations in neurogenesis that correlate with behavioral and cognitive symptoms have been observed and are modulated with pro- or anti-neurogenic stimuli45. Ultimately, the ability to track neurogenesis in longitudinal studies of living human brains will allow researchers to establish the importance of this process in physiology and disease, ultimately impacting the diagnosis and therapy of CNS disorders.…”

Adult neurogenesis and neurodegenerative diseases: A systems biology perspective

“…Even though the molecular mechanisms underlying this process remain unclear, adult hippocampal neurogenesis plays a significant role in learning and memory formation, and it is affected by environmental changes and disease conditions [Costa et al, 2015]. There are multiple modulators that affect the formation of newborn neurons such as neurotrophic factors, cytokines and chemokines, epigenetic factors, and signaling pathways.…”