title: 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.
authors.affiliation: Roche Pharmaceutical Research and Early Development, Neuroscience Ophthalmology and Rare Diseases (NORD), Roche Innovation Center Basel, 124 Grenzacherstrasse, 4070, Basel, Switzerland.
authors.forename: Veronica
authors.initials: V
authors.lastname: Costa
authors.forename: Sebastian
authors.initials: S
authors.lastname: Lugert
authors.forename: Ravi
authors.initials: R
authors.lastname: Jagasia
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D015195:Drug Design; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D058990:Molecular Targeted Therapy; D055495:Neurogenesis / Q000187:drug effects*; D018697:Nootropic Agents / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D015415:Biomarkers; D018697:Nootropic Agents