Neural stem cells as therapeutic agents for age‐related brain repair

Neurogenesis occurs in two germinal centres of the adult brain and persists with increasing age, although at a reduced level. This observation, that the mature brain can support neurogenesis, has given rise to the hope that neural stem cells could be used to repair the brain by repopulating regions suffering from neuronal loss as a result of injury or disease. The aging brain is vulnerable to mild cognitive impairment, increasing incidence of stroke, and a variety of neurodegenerative diseases. However, most studies to date have focused on the young adult brain, and relatively little information is available about the regulation of neurogenesis in the aged brain or the potential of using neural stem cells to repair the aged brain. This review summarizes the current state of knowledge on neurogenesis in the young adult brain and discusses the information available on age‐related changes in neurogenesis. Possible therapeutic strategies using neural stem cells for repair of the aging brain are considered.

[1]  D. Peterson Umbilical cord blood cells and brain stroke injury: bringing in fresh blood to address an old problem. , 2004, The Journal of clinical investigation.

[2]  H. Naritomi,et al.  Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. , 2004, The Journal of clinical investigation.

[3]  P. Hof,et al.  The presenilin-1 familial Alzheimer disease mutant P117L impairs neurogenesis in the hippocampus of adult mice , 2004, Experimental Neurology.

[4]  M. Gallagher,et al.  Neurogenesis in a rat model of age‐related cognitive decline , 2004, Aging cell.

[5]  P. Brundin,et al.  No evidence for new dopaminergic neurons in the adult mammalian substantia nigra. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Laurenz Wiskott,et al.  Functional significance of adult neurogenesis , 2004, Current Opinion in Neurobiology.

[7]  A. Benraiss,et al.  Adenovirally Expressed Noggin and Brain-Derived Neurotrophic Factor Cooperate to Induce New Medium Spiny Neurons from Resident Progenitor Cells in the Adult Striatal Ventricular Zone , 2004, The Journal of Neuroscience.

[8]  Marian Joëls,et al.  Prominent decline of newborn cell proliferation, differentiation, and apoptosis in the aging dentate gyrus, in absence of an age-related hypothalamus–pituitary–adrenal axis activation , 2004, Neurobiology of Aging.

[9]  Mitchel S. Berger,et al.  Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration , 2004, Nature.

[10]  Mark A Sussman,et al.  Myocardial aging and senescence: where have the stem cells gone? , 2004, Annual review of physiology.

[11]  Lin Xie,et al.  Increased hippocampal neurogenesis in Alzheimer's disease , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[12]  D. Peterson,et al.  A neurogenic theory of depression gains momentum. , 2003, Molecular interventions.

[13]  D. Abrous,et al.  Spatial memory performances of aged rats in the water maze predict levels of hippocampal neurogenesis , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[14]  M. Moskowitz,et al.  FGF-2 regulates neurogenesis and degeneration in the dentate gyrus after traumatic brain injury in mice. , 2003, The Journal of clinical investigation.

[15]  D. Peterson,et al.  Neurogenesis and brain injury: managing a renewable resource for repair. , 2003, The Journal of clinical investigation.

[16]  Michael Dragunow,et al.  Increased cell proliferation and neurogenesis in the adult human Huntington's disease brain , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[17]  M. Gallagher,et al.  Production of new cells in the rat dentate gyrus over the lifespan: relation to cognitive decline , 2003, The European journal of neuroscience.

[18]  Oleg Shupliakov,et al.  Evidence for neurogenesis in the adult mammalian substantia nigra , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[19]  K. Jin,et al.  Neurogenesis and aging: FGF‐2 and HB‐EGF restore neurogenesis in hippocampus and subventricular zone of aged mice , 2003, Aging cell.

[20]  Alan Carleton,et al.  Becoming a new neuron in the adult olfactory bulb , 2003, Nature Neuroscience.

[21]  M. Tuszynski,et al.  Hippocampal cell genesis does not correlate with spatial learning ability in aged rats , 2003, The Journal of comparative neurology.

[22]  A. Mikami,et al.  Nonrenewal of Neurons in the Cerebral Neocortex of Adult Macaque Monkeys , 2003, The Journal of Neuroscience.

[23]  M. Mattson,et al.  Disruption of neurogenesis by amyloid β‐peptide, and perturbed neural progenitor cell homeostasis, in models of Alzheimer's disease , 2002, Journal of neurochemistry.

[24]  O. Lindvall,et al.  Neuronal replacement from endogenous precursors in the adult brain after stroke , 2002, Nature Medicine.

[25]  M. Nakafuku,et al.  Regeneration of Hippocampal Pyramidal Neurons after Ischemic Brain Injury by Recruitment of Endogenous Neural Progenitors , 2002, Cell.

[26]  F. Gage,et al.  The Adult Substantia Nigra Contains Progenitor Cells with Neurogenic Potential , 2002, The Journal of Neuroscience.

[27]  G. Kempermann,et al.  Neuroplasticity in old age: Sustained fivefold induction of hippocampal neurogenesis by long‐term environmental enrichment , 2002, Annals of neurology.

[28]  Hartmut Geiger,et al.  The aging of lympho-hematopoietic stem cells , 2002, Nature Immunology.

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

[30]  A. Shetty,et al.  Combined neurotrophic supplementation and caspase inhibition enhances survival of fetal hippocampal CA3 cell grafts in lesioned CA3 region of the aging hippocampus , 2002, Neuroscience.

[31]  Fred H. Gage,et al.  Neurogenesis in the Adult Brain , 2002, The Journal of Neuroscience.

[32]  D. Peterson Stem cells in brain plasticity and repair. , 2002, Current opinion in pharmacology.

[33]  Mark P Mattson,et al.  Dietary restriction enhances neurotrophin expression and neurogenesis in the hippocampus of adult mice , 2002, Journal of neurochemistry.

[34]  P. Rakic,et al.  Cell Proliferation Without Neurogenesis in Adult Primate Neocortex , 2001, Science.

[35]  S. Bennett,et al.  Intracerebroventricular infusion of insulin-like growth factor-I ameliorates the age-related decline in hippocampal neurogenesis , 2001, Neuroscience.

[36]  A. Benraiss,et al.  Adenoviral Brain-Derived Neurotrophic Factor Induces Both Neostriatal and Olfactory Neuronal Recruitment from Endogenous Progenitor Cells in the Adult Forebrain , 2001, The Journal of Neuroscience.

[37]  Stanley J. Wiegand,et al.  Infusion of Brain-Derived Neurotrophic Factor into the Lateral Ventricle of the Adult Rat Leads to New Neurons in the Parenchyma of the Striatum, Septum, Thalamus, and Hypothalamus , 2001, The Journal of Neuroscience.

[38]  C. Gross,et al.  Adult-generated hippocampal and neocortical neurons in macaques have a transient existence , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[39]  M. Moskowitz,et al.  FGF-2 regulation of neurogenesis in adult hippocampus after brain injury , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[40]  Eric J. Nestler,et al.  Chronic Antidepressant Treatment Increases Neurogenesis in Adult Rat Hippocampus , 2000, The Journal of Neuroscience.

[41]  Blair R. Leavitt,et al.  Induction of neurogenesis in the neocortex of adult mice , 2000, Nature.

[42]  P. Eriksson,et al.  Peripheral Infusion of IGF-I Selectively Induces Neurogenesis in the Adult Rat Hippocampus , 2000, The Journal of Neuroscience.

[43]  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.

[44]  R. McKay,et al.  Restoring production of hippocampal neurons in old age , 1999, Nature Neuroscience.

[45]  I. Black,et al.  Stimulation of Neonatal and Adult Brain Neurogenesis by Subcutaneous Injection of Basic Fibroblast Growth Factor , 1999, The Journal of Neuroscience.

[46]  F. Gage,et al.  Adult‐generated neurons in the dentate gyrus send axonal projections to field CA3 and are surrounded by synaptic vesicles , 1999, The Journal of comparative neurology.

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

[48]  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.

[49]  Gerd Kempermann,et al.  Experience-Induced Neurogenesis in the Senescent Dentate Gyrus , 1998, The Journal of Neuroscience.

[50]  B. Mcewen,et al.  Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[51]  F. Gage,et al.  Epidermal Growth Factor and Fibroblast Growth Factor-2 Have Different Effects on Neural Progenitors in the Adult Rat Brain , 1997, The Journal of Neuroscience.

[52]  F. Gage,et al.  More hippocampal neurons in adult mice living in an enriched environment , 1997, Nature.

[53]  F. Gage,et al.  Differentiation of adult hippocampus-derived progenitors into olfactory neurons in vivo , 1996, Nature.

[54]  T. Palmer,et al.  Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

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

[56]  F. Gage,et al.  Proliferation, differentiation, and long-term culture of primary hippocampal neurons. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[57]  S. Weiss,et al.  Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. , 1992, Science.

[58]  A. Shetty,et al.  Fetal hippocampal CA3 cell grafts enriched with fibroblast growth factor‐2 exhibit enhanced neuronal integration into the lesioned aging rat hippocampus in a kainate model of temporal lobe epilepsy , 2003, Hippocampus.

[59]  F. Gage,et al.  Retinoic acid and neurotrophins collaborate to regulate neurogenesis in adult-derived neural stem cell cultures. , 1999, Journal of neurobiology.