Role of the cholinergic system in regulating survival of newborn neurons in the adult mouse dentate gyrus and olfactory bulb

Neurogenesis in the subgranular zone of the hippocampal dentate gyrus and olfactory bulbs continues into adulthood and has been implicated in the cognitive function of the adult brain. The basal forebrain cholinergic system has been suggested to play a role in regulating neurogenesis as well as learning and memory in these regions. Herein, we report that highly polysialylated neural cell adhesion molecule (PSA‐NCAM)‐positive immature cells as well as neuronal nuclei (NeuN)‐positive mature neurons in the dentate gyrus and olfactory bulb express multiple acetylcholine receptor subunits and make contact with cholinergic fibers. To examine the function of acetylcholine in neurogenesis, we used donepezil (Aricept), a potent and selective acetylcholinesterase inhibitor that improves cognitive impairment in Alzheimer's disease. Intraperitoneal administrations of donepezil significantly enhanced the survival of newborn neurons, but not proliferation of neural progenitor cells in the subgranular zone or the subventricular zone of normal mice. Moreover, donepezil treatment reversed the chronic stress‐induced decrease in neurogenesis. Taken together, these results suggest that activation of the cholinergic system promotes survival of newborn neurons in the adult dentate gyrus and olfactory bulb under both normal and stressed conditions.

[1]  O. Lindvall,et al.  Forebrain acetylcholine regulates adult hippocampal neurogenesis and learning , 2005, Neurobiology of Aging.

[2]  S. Rogers,et al.  Age-related loss of neuronal nicotinic receptor expression in the aging mouse hippocampus corresponds with cyclooxygenase-2 and PPAR gamma expression and is altered by long-term NS398 administration. , 2005, Journal of neurobiology.

[3]  M. Picciotto,et al.  Alteration of hippocampal cell proliferation in mice lacking the β2 subunit of the neuronal nicotinic acetylcholine receptor , 2004, Synapse.

[4]  J. Winkler,et al.  Decreased neurogenesis after cholinergic forebrain lesion in the adult rat , 2004, Journal of neuroscience research.

[5]  G. Wenk,et al.  The toxicity of tumor necrosis factor-α upon cholinergic neurons within the nucleus basalis and the role of norepinephrine in the regulation of inflammation: implications for alzheimer's disease , 2003, Neuroscience.

[6]  S. Scheff,et al.  Chronic intermittent nicotine administration attenuates traumatic brain injury-induced cognitive dysfunction , 2003, Neuroscience.

[7]  T. Madsen,et al.  Arrested neuronal proliferation and impaired hippocampal function following fractionated brain irradiation in the adult rat , 2003, Neuroscience.

[8]  H. Cameron,et al.  Short‐term and long‐term survival of new neurons in the rat dentate gyrus , 2003, The Journal of comparative neurology.

[9]  L. Calzà,et al.  Neural stem cells and cholinergic neurons: Regulation by immunolesion and treatment with mitogens, retinoic acid, and nerve growth factor , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[10]  F. Gage,et al.  Enriched environment and physical activity stimulate hippocampal but not olfactory bulb neurogenesis , 2003, The European journal of neuroscience.

[11]  David A. Johnson,et al.  Estrogen enhances potassium-stimulated acetylcholine release in the rat hippocampus , 2003, Brain Research.

[12]  P. Hof,et al.  Repeated restraint stress suppresses neurogenesis and induces biphasic PSA‐NCAM expression in the adult rat dentate gyrus , 2003, The European journal of neuroscience.

[13]  M. Mattson,et al.  Meal size and frequency affect neuronal plasticity and vulnerability to disease: cellular and molecular mechanisms , 2003, Journal of neurochemistry.

[14]  M. Gallagher,et al.  Effects of cholinergic lesions produced by infusions of 192 IgG-saporin on glucocorticoid receptor mRNA expression in hippocampus and medial prefrontal cortex of the rat , 2002, Neuroscience.

[15]  S. Scheff,et al.  Time-dependent changes in rat brain cholinergic receptor expression after experimental brain injury. , 2002, Journal of neurotrauma.

[16]  N. Toschi,et al.  Chronic psychosocial stress and concomitant repetitive transcranial magnetic stimulation: effects on stress hormone levels and adult hippocampal neurogenesis , 2002, Biological Psychiatry.

[17]  M. Gallagher,et al.  Decreased glucocorticoid receptor mRNA and dysfunction of HPA axis in rats after removal of the cholinergic innervation to hippocampus. , 2002, The European journal of neuroscience.

[18]  M. Mattson,et al.  Evidence that brain‐derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice , 2002, Journal of neurochemistry.

[19]  Taeck-Hyun Lee,et al.  Alcohol and nicotine reduce cell proliferation and enhance apoptosis in dentate gyrus , 2002, Neuroreport.

[20]  Arturo Alvarez-Buylla,et al.  Maturation and Death of Adult-Born Olfactory Bulb Granule Neurons: Role of Olfaction , 2002, The Journal of Neuroscience.

[21]  C. Cotman,et al.  Hippocampal brain‐derived neurotrophic factor gene regulation by exercise and the medial septum , 2002, Journal of neuroscience research.

[22]  D. Abrous,et al.  Nicotine Self-Administration Impairs Hippocampal Plasticity , 2002, The Journal of Neuroscience.

[23]  Christelle Rochefort,et al.  Enriched Odor Exposure Increases the Number of Newborn Neurons in the Adult Olfactory Bulb and Improves Odor Memory , 2002, The Journal of Neuroscience.

[24]  F. Gage,et al.  Functional neurogenesis in the adult hippocampus , 2002, Nature.

[25]  M. Banasr,et al.  Serotonin mediates oestrogen stimulation of cell proliferation in the adult dentate gyrus , 2001, The European journal of neuroscience.

[26]  E Gould,et al.  Exposure to fox odor inhibits cell proliferation in the hippocampus of adult rats via an adrenal hormone‐dependent mechanism , 2001, The Journal of comparative neurology.

[27]  H. Shibasaki,et al.  α7 Nicotinic Receptor Transduces Signals to Phosphatidylinositol 3-Kinase to Block A β-Amyloid-induced Neurotoxicity* , 2001, The Journal of Biological Chemistry.

[28]  E. Gould,et al.  Neurogenesis in the adult is involved in the formation of trace memories , 2001, Nature.

[29]  Bernhard Hennig,et al.  Nicotine protects against arachidonic‐acid‐induced caspase activation, cytochrome c release and apoptosis of cultured spinal cord neurons , 2001, Journal of neurochemistry.

[30]  T. Insel,et al.  Increased Number of BrdU-Labeled Neurons in the Rostral Migratory Stream of the Estrous Prairie Vole , 2001, Hormones and Behavior.

[31]  M. Prendergast,et al.  Chronic nicotine exposure reduces N-methyl-d-aspartate receptor-mediated damage in the hippocampus without altering calcium accumulation or extrusion: evidence of calbindin-D28K overexpression , 2001, Neuroscience.

[32]  J. Nyengaard,et al.  Cellular Expression of α7 Nicotinic Acetylcholine Receptor Protein in the Temporal Cortex in Alzheimer's and Parkinson's Disease— A Stereological Approach , 2000, Neurobiology of Disease.

[33]  J. Langston,et al.  Localization of nicotinic receptor subunit mRNAs in monkey brain by in situ hybridization , 2000, The Journal of comparative neurology.

[34]  L. Thal,et al.  Nicotinic receptor losses in dementia with Lewy bodies: comparisons with Alzheimer’s disease , 2000, Neurobiology of Aging.

[35]  C. Barnes,et al.  Chronic treatment of old rats with donepezil or galantamine: effects on memory, hippocampal plasticity and nicotinic receptors , 2000, Neuroscience.

[36]  F. Jourdan,et al.  Acetylcholine induces neuritic outgrowth in rat primary olfactory bulb cultures , 2000, Neuroscience.

[37]  J. Barker,et al.  Acetylcholine stimulates cortical precursor cell proliferation in vitro via muscarinic receptor activation and MAP kinase phosphorylation , 2000, The European journal of neuroscience.

[38]  H. Schröder,et al.  Quantitative assessment of nicotinic acetylcholine receptor proteins in the cerebral cortex of Alzheimer patients. , 2000, Brain research. Molecular brain research.

[39]  J. Vincent,et al.  Importance of newly generated neurons in the adult olfactory bulb for odor discrimination. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[40]  T J Sejnowski,et al.  Running enhances neurogenesis, learning, and long-term potentiation in mice. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[41]  Y. Endo,et al.  A long-term stress exposure impairs maze learning performance in rats , 1999, Neuroscience Letters.

[42]  Y. Kuriya,et al.  Effect of donepezil hydrochloride (E2020) on basal concentration of extracellular acetylcholine in the hippocampus of rats. , 1999, European journal of pharmacology.

[43]  E. Gould,et al.  Learning enhances adult neurogenesis in the hippocampal formation , 1999, Nature Neuroscience.

[44]  A. Levey,et al.  Muscarinic receptor subtypes involved in hippocampal circuits. , 1999, Life sciences.

[45]  F. Gage,et al.  Neurogenesis in the adult human hippocampus , 1998, Nature Medicine.

[46]  F. Gage,et al.  Nicotinic Receptor-Induced Apoptotic Cell Death of Hippocampal Progenitor Cells , 1998, The Journal of Neuroscience.

[47]  Stanley J. Wiegand,et al.  Intraventricular Administration of BDNF Increases the Number of Newly Generated Neurons in the Adult Olfactory Bulb , 1998, Molecular and Cellular Neuroscience.

[48]  N. Birdsall,et al.  International Union of Pharmacology. XVII. Classification of muscarinic acetylcholine receptors. , 1998, Pharmacological reviews.

[49]  J. Changeux,et al.  Brain nicotinic receptors: structure and regulation, role in learning and reinforcement 1 Published on the World Wide Web on 24 October 1997. 1 , 1998, Brain Research Reviews.

[50]  S. Shimohama,et al.  Nicotinic α7 receptors protect against glutamate neurotoxicity and neuronal ischemic damage , 1998, Brain Research.

[51]  R. Mohs,et al.  A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease , 1998, Neurology.

[52]  S. Shimohama,et al.  Nicotinic receptor stimulation protects neurons against β‐amyloid toxicity , 1997 .

[53]  M. Sekiguchi.  Genes to cells: edited by Jun-ichi Tomizawa, Blackwell Science Ltd. Institutional: £218.00 (Europe), £242.00 (Rest of World), US$382.00 (USA and Canada). Individual: £65.00 (Europe), £72.00 (Rest of World), US$114.00 (USA and Canada) ISSN 1356 9597 , 1997 .

[54]  E. Gould,et al.  Neurogenesis in the Dentate Gyrus of the Adult Tree Shrew Is Regulated by Psychosocial Stress and NMDA Receptor Activation , 1997, The Journal of Neuroscience.

[55]  A. Álvarez-Buylla,et al.  Network of tangential pathways for neuronal migration in adult mammalian brain. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[56]  L. Friedhoff,et al.  The efficacy and safety of donepezil in patients with Alzheimer's disease: Results of a US multicentre, randomized, double-blind, placebo-controlled trial , 1996 .

[57]  T. Seki,et al.  Age‐related production of new granule cells in the adult dentate gyrus , 1995, Neuroreport.

[58]  F. Jourdan,et al.  Comparative laminar distribution of various autoradiographic cholinergic markers in adult rat main olfactory bulb , 1995, Journal of Chemical Neuroanatomy.

[59]  H. Cameron,et al.  Regulation of adult neurogenesis by excitatory input and NMDA receptor activation in the dentate gyrus , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[60]  A. Levey,et al.  Expression of m1-m4 muscarinic acetylcholine receptor proteins in rat hippocampus and regulation by cholinergic innervation , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[61]  A. Björklund,et al.  Selective Lesioning of the Basal Forebrain Cholinergic System by Intraventricular 192 IgG–saporin: Behavioural, Biochemical and Stereological Studies in the Rat , 1995, The European journal of neuroscience.

[62]  M. Meaney,et al.  Enduring effects of chronic corticosterone treatment on spatial learning, synaptic plasticity, and hippocampal neuropathology in young and mid-aged rats , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[63]  N. Ravel,et al.  Scopolamine injection into the olfactory bulb impairs short-term olfactory memory in rats. , 1994, Behavioral neuroscience.

[64]  Bruce S. McEwen,et al.  Repeated stress causes reversible impairments of spatial memory performance , 1994, Brain Research.

[65]  H. Cameron,et al.  Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat , 1993, Neuroscience.

[66]  Maria B. Luskin,et al.  Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone , 1993, Neuron.

[67]  T. Seki,et al.  Highly polysialylated neural cell adhesion molecule (NCAM-H) is expressed by newly generated granule cells in the dentate gyrus of the adult rat , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[68]  J. Patrick,et al.  Molecular cloning, functional properties, and distribution of rat brain alpha 7: a nicotinic cation channel highly permeable to calcium , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[69]  L. Bonfanti,et al.  Mapping of the distribution of polysialylated neural cell adhesion molecule throughout the central nervous system of the adult rat: An immunohistochemical study , 1992, Neuroscience.

[70]  L. Butcher,et al.  Impairment of radial-arm maze performance in rats following lesions involving the cholinergic medial pathway: Reversal by arecoline and differential effects of muscarinic and nicotinic antagonists , 1991, Neuroscience.

[71]  Y. Endo,et al.  Acetylcholine release in the rat hippocampus as measured by the microdialysis method correlates with motor activity and exhibits a diurnal variation , 1991, Neuroscience.

[72]  H. Fibiger.  Cholinergic mechanisms in learning, memory and dementia: a review of recent evidence , 1991, Trends in Neurosciences.

[73]  H. Fibiger,et al.  Cholinergic activity in the rat hippocampus, cortex and striatum correlates with locomotor activity: An in vivo microdialysis study , 1991, Pharmacology Biochemistry and Behavior.

[74]  A. Nordberg,et al.  Tetrahydroaminoacridine induces opposite changes in muscarinic and nicotinic receptors in rat brain. , 1990, European journal of pharmacology.

[75]  J Patrick,et al.  Distribution of alpha2, alpha3, alpha4, and beta2 neuronal nicotinic receptor subunit mRNAs in the central nervous system: A hybridization histochemical study in the rat , 1989, The Journal of comparative neurology.

[76]  F. Gage,et al.  Continuous infusion of nerve growth factor prevents basal forebrain neuronal death after fimbria fornix transection. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[77]  F. Hefti,et al.  Nerve growth factor promotes survival of septal cholinergic neurons after fimbrial transections , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[78]  L. Heimer,et al.  Cholinergic and GABAergic afferents to the olfactory bulb in the rat with special emphasis on the projection neurons in the nucleus of the horizontal limb of the diagonal band , 1986, The Journal of comparative neurology.

[79]  Michael Frotscher,et al.  Cholinergic innervation of the rat hippocampus as revealed by choline acetyltransferase immunocytochemistry: A combined light and electron microscopic study , 1985, The Journal of comparative neurology.

[80]  S. Marotta,et al.  Cholinergic influences on hypothalamic-pituitary-adrenocortical activity of stressed rats: an approach utilizing agonists and antagonists. , 1978, Acta endocrinologica.

[81]  U. Meyer,et al.  Centrifugal cholinergic connections in the olfactory system of rats , 1977, Neuroscience.

[82]  J. Hinds,et al.  Neurogenesis in the adult rat: electron microscopic analysis of light radioautographs. , 1977, Science.

[83]  J. Altman.  Autoradiographic and histological studies of postnatal neurogenesis. IV. Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb , 1969, The Journal of comparative neurology.

[84]  Nihon Hassei Seibutsu Gakkai,et al.  Genes to cells , 1996 .

[85]  L. Friedhoff,et al.  The efficacy and safety of donepezil in patients with Alzheimer's disease: results of a US Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial. The Donepezil Study Group. , 1996, Dementia.

[86]  M. Frotscher,et al.  The cholinergic innervation of the rat fascia dentata: Identification of target structures on granule cells by combining choline acetyltransferase immunocytochemistry and Golgi impregnation , 1986, The Journal of comparative neurology.