Skip to main content
Log in

Effects of brain insults and pharmacological manipulations on the adult hippocampal neurogenesis

  • Review
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

During the last two decades, neurogenesis in the adult mammalian brain has been extensively investigated. Studies have indicated that two brain regions, the subgranular zone of the hippocampal dentate gyrus and the subventricular zone of the lateral ventricle, possess the most active progenitor cells that are capable of generating neurons throughout the lifespan of human beings. Adult hippocampal neurogenesis is the focus of this review. We intend to discuss the changes in the hippocampal neurogenesis caused by pathologic brain insults such as brain ischemia, traumatic brain injury, epileptic seizures, neurodegenerative disorder, and psychiatric diseases. Further, we discuss the stimulatory and inhibitory actions on adult hippocampal neurogenesis by biochemicals and pharmacological agents, including antidepressants, antipsychotics, agonists and antagonists of glutamate and GABA, adrenal corticoids, gonadal hormones, growth factors such as insulin-like growth factor I, erythropoietin, and drugs of abuse, including nicotine, alcohol, opiates, cocaine, methamphetamine, and 3,4-methylenedioxymethamphetamine (“ecstasy”).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Aberg, M. A., Aberg, N. D., Hedbacker, H., Oscarsson, J., and Eriksson, P. S., Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus. J. Neurosci., 20, 2896–2903 (2000).

    CAS  PubMed  Google Scholar 

  • Abrous, D. N., Adriani, W., Montaron, M. F., Aurousseau, C., Rougon, G., Le Moal, M., and Piazza, P. V., Nicotine selfadministration impairs hippocampal plasticity. J. Neurosci., 22, 3656–3662 (2002).

    CAS  PubMed  Google Scholar 

  • Altman, J., Are new neurons formed in the brains of adult mammals? Science, 135, 1127–1128 (1962).

    Article  CAS  PubMed  Google Scholar 

  • Alvarez-Buylla, A., Mechanism of neurogenesis in adult avian brain. Experientia, 46, 948–955 (1990).

    Article  CAS  PubMed  Google Scholar 

  • Alvarez-Buylla, A., Neurogenesis and plasticity in the CNS of adult birds. Exp. Neurol., 115, 110–114 (1992).

    Article  CAS  PubMed  Google Scholar 

  • Alvarez-Buylla, A. and Garcia-Verdugo, J. M., Neurogenesis in adult subventricular zone. J. Neurosci., 22, 629–634 (2002).

    CAS  PubMed  Google Scholar 

  • Amrein, I. and Slomianka, L., A morphologically distinct granule cell type in the dentate gyrus of the red fox correlates with adult hippocampal neurogenesis. Brain Res., 1328, 12–24 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Anderson, M. F., Aberg, M. A., Nilsson, M., and Eriksson, P. S., Insulin-like growth factor-I and neurogenesis in the adult mammalian brain. Brain Res. Dev. Brain Res., 134, 115–122 (2002).

    Article  CAS  PubMed  Google Scholar 

  • Banasr, M., Valentine, G. W., Li, X. Y., Gourley, S. L., Taylor, J. R., and Duman, R. S., Chronic unpredictable stress decreases cell proliferation in the cerebral cortex of the adult rat. Biol. Psychiatry, 62, 496–504 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Bayer, S. A., Yackel, J. W., and Puri, P. S., Neurons in the rat dentate gyrus granular layer substantially increase during juvenile and adult life. Science, 216, 890–892 (1982).

    Article  CAS  PubMed  Google Scholar 

  • Bengzon, J., Kokaia, Z., Elmer, E., Nanobashvili, A., Kokaia, M., and Lindvall, O., Apoptosis and proliferation of dentate gyrus neurons after single and intermittent limbic seizures. Proc. Natl. Acad. Sci. U. S. A., 94, 10432–10437 (1997).

    Article  CAS  PubMed  Google Scholar 

  • Bernabeu, R. and Sharp, F. R., NMDA and AMPA/kainate glutamate receptors modulate dentate neurogenesis and CA3 synapsin-I in normal and ischemic hippocampus. J. Cereb. Blood Flow Metab., 20, 1669–1680 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Brezun, J. M. and Daszuta, A., Depletion in serotonin decreases neurogenesis in the dentate gyrus and the subventricular zone of adult rats. Neuroscience, 89, 999–1002 (1999).

    Article  CAS  PubMed  Google Scholar 

  • Brines, M. L., Ghezzi, P., Keenan, S., Agnello, D., de Lanerolle, N. C., Cerami, C., Itri, L. M., and Cerami, A., Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury. Proc. Natl. Acad. Sci. U. S. A., 97, 10526–10531 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Bruel-Jungerman, E., Davis, S., Rampon, C., and Laroche, S., Long-term potentiation enhances neurogenesis in the adult dentate gyrus. J. Neurosci., 26, 5888–5893 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Brummelte, S. and Galea, L. A., Chronic high corticosterone reduces neurogenesis in the dentate gyrus of adult male and female rats. Neuroscience, 168, 680–690 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Cameron, H. A., Woolley, C. S., McEwen, B. S., and Gould, E., Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat. Neuroscience, 56, 337–344 (1993).

    Article  CAS  PubMed  Google Scholar 

  • Cameron, H. A. and Gould, E., Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus. Neuroscience, 61, 203–209 (1994).

    Article  CAS  PubMed  Google Scholar 

  • Cameron, H. A., McEwen, B. S., and Gould, E., Regulation of adult neurogenesis by excitatory input and NMDA receptor activation in the dentate gyrus. J. Neurosci., 15, 4687–4692 (1995).

    CAS  PubMed  Google Scholar 

  • Cameron, H. A., Hazel, T. G., and McKay, R. D., Regulation of neurogenesis by growth factors and neurotransmitters. J. Neurobiol., 36, 287–306 (1998a).

    Article  CAS  PubMed  Google Scholar 

  • Cameron, H. A., Tanapat, P., and Gould, E., Adrenal steroids and N-methyl-D-aspartate receptor activation regulate neurogenesis in the dentate gyrus of adult rats through a common pathway. Neuroscience, 82, 349–354 (1998b).

    Article  CAS  PubMed  Google Scholar 

  • Catlow, B. J., Badanich, K. A., Sponaugle, A. E., Rowe, A. R., Song, S., Rafalovich, I., Sava, V., Kirstein, C. L., and Sanchez-Ramos, J., Effects of MDMA (“ecstasy“) during adolescence on place conditioning and hippocampal neurogenesis. Eur. J. Pharmacol., 628, 96–103 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Chang, Y. S., Mu, D., Wendland, M., Sheldon, R. A., Vexler, Z. S., McQuillen, P. S., and Ferriero, D. M., Erythropoietin improves functional and histological outcome in neonatal stroke. Pediatr. Res., 58, 106–111 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Chen, G., Rajkowska, G., Du, F., Seraji-Bozorgzad, N., and Manji, H. K., Enhancement of hippocampal neurogenesis by lithium. J. Neurochem., 75, 1729–1734 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Chevallier, N. L., Soriano, S., Kang, D. E., Masliah, E., Hu, G., and Koo, E. H., Perturbed neurogenesis in the adult hippocampus associated with presenilin-1 A246E mutation. Am. J. Pathol., 167, 151–159 (2005).

    CAS  PubMed  Google Scholar 

  • Chiou, S. H., Ku, H. H., Tsai, T. H., Lin, H. L., Chen, L. H., Chien, C. S., Ho, L. L., Lee, C. H., and Chang, Y. L., Moclobemide upregulated Bcl-2 expression and induced neural stem cell differentiation into serotoninergic neuron via extracellular-regulated kinase pathway. Br. J. Pharmacol., 148, 587–598 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Chirumamilla, S., Sun, D., Bullock, M. R., and Colello, R. J., Traumatic brain injury induced cell proliferation in the adult mammalian central nervous system. J. Neurotrauma, 19, 693–703 (2002).

    Article  CAS  PubMed  Google Scholar 

  • Cho, K. O., Kim, S. K., Rhee, G. S., Kwack, S. J., Cho, D. H., Sung, K. W., and Kim, S. Y., Chronic 3,4-methylenedioxymethamphetamine treatment suppresses cell proliferation in the adult mouse dentate gyrus. Eur. J. Pharmacol., 566, 120–123 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Cho, K. O., Rhee, G. S., Kwack, S. J., Chung, S. Y., and Kim, S. Y., Developmental exposure to 3,4-methylenedioxy-methamphetamine results in downregulation of neurogenesis in the adult mouse hippocampus. Neuroscience, 154, 1034–1041 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Choi, Y. S., Lee, M. Y., Sung, K. W., Jeong, S. W., Choi, J. S., Park, H. J., Kim, O. N., Lee, S. B., and Kim, S. Y., Regional differences in enhanced neurogenesis in the dentate gyrus of adult rats after transient forebrain ischemia. Mol. Cells, 16, 232–238 (2003).

    CAS  PubMed  Google Scholar 

  • Choi, Y. S., Cho, K. O., and Kim, S. Y., Asymmetry in enhanced neurogenesis in the rostral dentate gyrus following kainic acid-induced status epilepticus in adult rats. Arch. Pharm. Res., 30, 646–652 (2007a).

    Article  CAS  PubMed  Google Scholar 

  • Choi, Y. S., Cho, K. O., and Kim, S. Y., Fluoxetine does not affect the ischemia-induced increase of neurogenesis in the adult rat dentate gyrus. Arch. Pharm. Res., 30, 641–645 (2007b).

    Article  CAS  PubMed  Google Scholar 

  • Chun, S. K., Sun, W., Park, J. J., and Jung, M. W., Enhanced proliferation of progenitor cells following long-term potentiation induction in the rat dentate gyrus. Neurobiol. Learn. Mem., 86, 322–329 (2006).

    Article  PubMed  Google Scholar 

  • Cossette, M., Bedard, A., and Parent, A., Dopaminergic neurons in human striatum and neurogenesis in adult monkey striatum. Ann. N. Y. Acad. Sci., 991, 346–349 (2003).

    Article  Google Scholar 

  • Dash, P. K., Mach, S. A., and Moore, A. N., Enhanced neurogenesis in the rodent hippocampus following traumatic brain injury. J. Neurosci. Res., 63, 313–319 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Dashtipour, K., Tran, P. H., Okazaki, M. M., Nadler, J. V., and Ribak, C. E., Ultrastructural features and synaptic connections of hilar ectopic granule cells in the rat dentate gyrus are different from those of granule cells in the granule cell layer. Brain Res., 890, 261–271 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Dawirs, R. R., Hildebrandt, K., and Teuchert-Noodt, G., Adult treatment with haloperidol increases dentate granule cell proliferation in the gerbil hippocampus. J. Neural Transm., 105, 317–327 (1998).

    Article  CAS  PubMed  Google Scholar 

  • Delgado-Gonzalez, F. J., Alonso-Fuentes, A., Delgado-Fumero, A., Garcia-Verdugo, J. M., Gonzalez-Granero, S., Trujillo-Trujillo, C. M., and Damas-Hernandez, M. C., Seasonal differences in ventricular proliferation of adult Gallotia galloti lizards. Brain Res., 1191, 39–46 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Derrick, B. E., York, A. D., and Martinez, J. L., Jr., Increased granule cell neurogenesis in the adult dentate gyrus following mossy fiber stimulation sufficient to induce long-term potentiation. Brain Res., 857, 300–307 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Dong, H., Goico, B., Martin, M., Csernansky, C. A., Bertchume, A., and Csernansky, J. G., Modulation of hippocampal cell proliferation, memory, and amyloid plaque deposition in APPsw (Tg2576) mutant mice by isolation stress. Neuroscience, 127, 601–609 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Donovan, M. H., Yazdani, U., Norris, R. D., Games, D., German, D. C., and Eisch, A. J., Decreased adult hippocampal neurogenesis in the PDAPP mouse model of Alzheimer’s disease. J. Comp. Neurol., 495, 70–83 (2006).

    Article  PubMed  Google Scholar 

  • Duman, R. S., Malberg, J., and Nakagawa, S., Regulation of adult neurogenesis by psychotropic drugs and stress. J. Pharmacol. Exp. Ther., 299, 401–407 (2001a).

    CAS  PubMed  Google Scholar 

  • Duman, R. S., Nakagawa, S., and Malberg, J., Regulation of adult neurogenesis by antidepressant treatment. Neuropsychopharmacology, 25, 836–844 (2001b).

    Article  CAS  PubMed  Google Scholar 

  • Duman, R. S., Depression: a case of neuronal life and death? Biol. Psychiatry, 56, 140–145 (2004).

    Article  PubMed  Google Scholar 

  • Eisch, A. J., Barrot, M., Schad, C. A., Self, D. W., and Nestler, E. J., Opiates inhibit neurogenesis in the adult rat hippocampus. Proc. Natl. Acad. Sci. U. S. A., 97, 7579–7584 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Eisch, A. J. and Harburg, G. C., Opiates, psychostimulants, and adult hippocampal neurogenesis: Insights for addiction and stem cell biology. Hippocampus, 16, 271–286 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Emery, D. L., Fulp, C. T., Saatman, K. E., Schutz, C., Neugebauer, E., and McIntosh, T. K., Newly born granule cells in the dentate gyrus rapidly extend axons into the hippocampal CA3 region following experimental brain injury. J. Neurotrauma, 22, 978–988 (2005).

    Article  PubMed  Google Scholar 

  • Eriksson, P. S., Perfilieva, E., Bjork-Eriksson, T., Alborn, A. M., Nordborg, C., Peterson, D. A., and Gage, F. H., Neurogenesis in the adult human hippocampus. Nat. Med., 4, 1313–1317 (1998).

    Article  CAS  PubMed  Google Scholar 

  • Fabel, K., Tam, B., Kaufer, D., Baiker, A., Simmons, N., Kuo, C. J., and Palmer, T. D., VEGF is necessary for exercise-induced adult hippocampal neurogenesis. Eur. J. Neurosci., 18, 2803–2812 (2003).

    Article  PubMed  Google Scholar 

  • Feng, Y., Weijdegard, B., Wang, T., Egecioglu, E., Fernandez-Rodriguez, J., Huhtaniemi, I., Stener-Victorin, E., Billig, H., and Shao, R., Spatiotemporal expression of androgen receptors in the female rat brain during the oestrous cycle and the impact of exogenous androgen administration: a comparison with gonadally intact males. Mol. Cell. Endocrinol., 321, 161–174 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Gage, F. H., Mammalian neural stem cells. Science, 287, 1433–1438 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Galea, L. A., Spritzer, M. D., Barker, J. M., and Pawluski, J. L., Gonadal hormone modulation of hippocampal neurogenesis in the adult. Hippocampus, 16, 225–232 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Ge, S., Goh, E. L., Sailor, K. A., Kitabatake, Y., Ming, G. L., and Song, H., GABA regulates synaptic integration of newly generated neurons in the adult brain. Nature, 439, 589–593 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Gil-Mohapel, J., Boehme, F., Kainer, L., and Christie, B. R., Hippocampal cell loss and neurogenesis after fetal alcohol exposure: Insights from different rodent models. Brain Res. Rev., 64, 283–303 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Glasper, E. R., Llorens-Martin, M. V., Leuner, B., Gould, E., and Trejo, J. L., Blockade of insulin-like growth factor-I has complex effects on structural plasticity in the hippocampus. Hippocampus, 20, 706–712 (2010).

    CAS  PubMed  Google Scholar 

  • Gould, E., Cameron, H. A., Daniels, D. C., Woolley, C. S., and McEwen, B. S., Adrenal hormones suppress cell division in the adult rat dentate gyrus. J. Neurosci., 12, 3642–3650 (1992).

    CAS  PubMed  Google Scholar 

  • Gould, E., McEwen, B. S., Tanapat, P., Galea, L. A., and Fuchs, E., Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. J. Neurosci., 17, 2492–2498 (1997).

    CAS  PubMed  Google Scholar 

  • Gould, E., Beylin, A., Tanapat, P., Reeves, A., and Shors, T. J., Learning enhances adult neurogenesis in the hippocampal formation. Nat. Neurosci., 2, 260–265 (1999a).

    Article  CAS  PubMed  Google Scholar 

  • Gould, E., Reeves, A. J., Fallah, M., Tanapat, P., Gross, C. G., and Fuchs, E., Hippocampal neurogenesis in adult Old World primates. Proc. Natl. Acad. Sci. U. S. A., 96, 5263–5267 (1999b).

    Article  CAS  PubMed  Google Scholar 

  • Gould, E. and Gross, C. G., Neurogenesis in adult mammals: some progress and problems. J. Neurosci., 22, 619–623 (2002).

    CAS  PubMed  Google Scholar 

  • Green, W., Patil, P., Marsden, C. A., Bennett, G. W., and Wigmore, P. M., Treatment with olanzapine increases cell proliferation in the subventricular zone and prefrontal cortex. Brain Res., 1070, 242–245 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Guzman-Marin, R., Suntsova, N., Methippara, M., Greiffenstein, R., Szymusiak, R., and McGinty, D., Sleep deprivation suppresses neurogenesis in the adult hippocampus of rats. Eur. J. Neurosci., 22, 2111–2116 (2005).

    Article  PubMed  Google Scholar 

  • Halim, N. D., Weickert, C. S., McClintock, B. W., Weinberger, D. R., and Lipska, B. K., Effects of chronic haloperidol and clozapine treatment on neurogenesis in the adult rat hippocampus. Neuropsychopharmacology, 29, 1063–1069 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Haughey, N. J., Nath, A., Chan, S. L., Borchard, A. C., Rao, M. S., and Mattson, M. P., Disruption of neurogenesis by amyloid beta-peptide, and perturbed neural progenitor cell homeostasis, in models of Alzheimer’s disease. J. Neurochem., 83, 1509–1524 (2002).

    Article  CAS  PubMed  Google Scholar 

  • Hernandez-Rabaza, V., Dominguez-Escriba, L., Barcia, J. A., Rosel, J. F., Romero, F. J., Garcia-Verdugo, J. M., and Canales, J. J., Binge administration of 3,4-methylenedi-oxymethamphetamine (“ecstasy”) impairs the survival of neural precursors in adult rat dentate gyrus. Neuropharmacology, 51, 967–973 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Hildebrandt, K., Teuchert-Noodt, G., and Dawirs, R. R., A single neonatal dose of methamphetamine suppresses dentate granule cell proliferation in adult gerbils which is restored to control values by acute doses of haloperidol. J. Neural Transm., 106, 549–558 (1999).

    Article  CAS  PubMed  Google Scholar 

  • Houser, C. R., Granule cell dispersion in the dentate gyrus of humans with temporal lobe epilepsy. Brain Res., 535, 195–204 (1990).

    Article  CAS  PubMed  Google Scholar 

  • Ieraci, A. and Herrera, D. G., Single alcohol exposure in early life damages hippocampal stem/progenitor cells and reduces adult neurogenesis. Neurobiol. Dis., 26, 597–605 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Isgor, C. and Watson, S. J., Estrogen receptor alpha and beta mRNA expressions by proliferating and differentiating cells in the adult rat dentate gyrus and subventricular zone. Neuroscience, 134, 847–856 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Jacobs, B. L., van Praag, H., and Gage, F. H., Adult brain neurogenesis and psychiatry: a novel theory of depression. Mol. Psychiatry, 5, 262–269 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Jin, K., Minami, M., Lan, J. Q., Mao, X. O., Batteur, S., Simon, R. P., and Greenberg, D. A., Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat. Proc. Natl. Acad. Sci. U. S. A., 98, 4710–4715 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Kaplan, M. S. and Hinds, J. W., Neurogenesis in the adult rat: electron microscopic analysis of light radioautographs. Science, 197, 1092–1094 (1977).

    Article  CAS  PubMed  Google Scholar 

  • Kaplan, M. S. and Bell, D. H., Mitotic neuroblasts in the 9-day-old and 11-month-old rodent hippocampus. J. Neurosci., 4, 1429–1441 (1984).

    CAS  PubMed  Google Scholar 

  • Kee, N., Teixeira, C. M., Wang, A. H., and Frankland, P. W., Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus. Nat. Neurosci., 10, 355–362 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Kee, N. J., Preston, E., and Wojtowicz, J. M., Enhanced neurogenesis after transient global ischemia in the dentate gyrus of the rat. Exp. Brain Res., 136, 313–320 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Keilhoff, G., Grecksch, G., Bernstein, H. G., Roskoden, T., and Becker, A., Risperidone and haloperidol promote survival of stem cells in the rat hippocampus. Eur. Arch. Psychiatry Clin. Neurosci., 260, 151–162 (2010).

    Article  PubMed  Google Scholar 

  • Kempermann, G., Kuhn, H. G., and Gage, F. H., Genetic influence on neurogenesis in the dentate gyrus of adult mice. Proc. Natl. Acad. Sci. U.S.A., 94, 10409–10414 (1997a).

    Article  CAS  PubMed  Google Scholar 

  • Kempermann, G., Kuhn, H. G., and Gage, F. H., More hippocampal neurons in adult mice living in an enriched environment. Nature, 386, 493–495 (1997b).

    Article  CAS  PubMed  Google Scholar 

  • Kempermann, G., Regulation of adult hippocampal neurogenesis — implications for novel theories of major depression. Bipolar Disord., 4, 17–33 (2002).

    Article  PubMed  Google Scholar 

  • Kempermann, G., Wiskott, L., and Gage, F. H., Functional significance of adult neurogenesis. Curr. Opin. Neurobiol., 14, 186–191 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Kernie, S. G., Erwin, T. M., and Parada, L. F., Brain remodeling due to neuronal and astrocytic proliferation after controlled cortical injury in mice. J. Neurosci. Res., 66, 317–326 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Kim, J. B., Ju, J. Y., Kim, J. H., Kim, T. Y., Yang, B. H., Lee, Y. S., and Son, H., Dexamethasone inhibits proliferation of adult hippocampal neurogenesis in vivo and in vitro. Brain Res., 1027, 1–10 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Klintsova, A. Y., Helfer, J. L., Calizo, L. H., Dong, W. K., Goodlett, C. R., and Greenough, W. T., Persistent impairment of hippocampal neurogenesis in young adult rats following early postnatal alcohol exposure. Alcohol. Clin. Exp. Res., 31, 2073–2082 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Kodama, M., Fujioka, T., and Duman, R. S., Chronic olanzapine or fluoxetine administration increases cell proliferation in hippocampus and prefrontal cortex of adult rat. Biol. Psychiatry, 56, 570–580 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Kuhn, H. G., Dickinson-Anson, H., and Gage, F. H., Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J. Neurosci., 16, 2027–2033 (1996).

    CAS  PubMed  Google Scholar 

  • Lavenex, P., Steele, M. A., and Jacobs, L. F., The seasonal pattern of cell proliferation and neuron number in the dentate gyrus of wild adult eastern grey squirrels. Eur. J. Neurosci., 12, 643–648 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Lee, J., Duan, W., and Mattson, M. P., 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. J. Neurochem., 82, 1367–1375 (2002).

    Article  CAS  PubMed  Google Scholar 

  • Lichtenwalner, R. J., Forbes, M. E., Bennett, S. A., Lynch, C. D., Sonntag, W. E., and Riddle, D. R., Intracerebroventricular infusion of insulin-like growth factor-I ameliorates the age-related decline in hippocampal neurogenesis. Neuroscience, 107, 603–613 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Liu, J., Solway, K., Messing, R. O., and Sharp, F. R., Increased neurogenesis in the dentate gyrus after transient global ischemia in gerbils. J. Neurosci., 18, 7768–7778 (1998).

    CAS  PubMed  Google Scholar 

  • Llorens-Martin, M., Torres-Aleman, I., and Trejo, J. L., Exercise modulates insulin-like growth factor 1-dependent and -independent effects on adult hippocampal neurogenesis and behaviour. Mol. Cell. Neurosci., 44, 109–117 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Lois, C. and Alvarez-Buylla, A., Long-distance neuronal migration in the adult mammalian brain. Science, 264, 1145–1148 (1994).

    Article  CAS  PubMed  Google Scholar 

  • Lois, C., Garcia-Verdugo, J.-M., and Alvarez-Buylla, A., Chain migration of neuronal precursors. Science, 271, 978–981 (1996).

    Article  CAS  PubMed  Google Scholar 

  • Lu, D., Mahmood, A., Qu, C., Goussev, A., Schallert, T., and Chopp, M., Erythropoietin enhances neurogenesis and restores spatial memory in rats after traumatic brain injury. J. Neurotrauma, 22, 1011–1017 (2005).

    Article  PubMed  Google Scholar 

  • Lucassen, P. J., Meerlo, P., Naylor, A. S., van Dam, A. M., Dayer, A. G., Fuchs, E., Oomen, C. A., and Czeh, B., Regulation of adult neurogenesis by stress, sleep disruption, exercise and inflammation: Implications for depression and antidepressant action. Eur. Neuropsychopharmacol., 20, 1–17 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Madsen, T. M., Treschow, A., Bengzon, J., Bolwig, T. G., Lindvall, O., and Tingstrom, A., Increased neurogenesis in a model of electroconvulsive therapy. Biol. Psychiatry, 47, 1043–1049 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Maekawa, M., Namba, T., Suzuki, E., Yuasa, S., Kohsaka, S., and Uchino, S., NMDA receptor antagonist memantine promotes cell proliferation and production of mature granule neurons in the adult hippocampus. Neurosci. Res., 63, 259–266 (2009).

    Article  CAS  PubMed  Google Scholar 

  • Magavi, S. S., Leavitt, B. R., and Macklis, J. D., Induction of neurogenesis in the neocortex of adult mice. Nature, 405, 951–955 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Malberg, J. E., Eisch, A. J., Nestler, E. J., and Duman, R. S., Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J. Neurosci., 20, 9104–9110 (2000).

    CAS  PubMed  Google Scholar 

  • Markwardt, S. and Overstreet-Wadiche, L., GABAergic signalling to adult-generated neurons. J. Physiol., 586, 3745–3749 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Marty, A. and Llano, I., Excitatory effects of GABA in established brain networks. Trends Neurosci., 28, 284–289 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Mello, L. E., Cavalheiro, E. A., Tan, A. M., Pretorius, J. K., Babb, T. L., and Finch, D. M., Granule cell dispersion in relation to mossy fiber sprouting, hippocampal cell loss, silent period and seizure frequency in the pilocarpine model of epilepsy. Epilepsy Res. Suppl., 9, 51–59 (1992).

    CAS  PubMed  Google Scholar 

  • Melvin, N. R., Spanswick, S. C., Lehmann, H., and Sutherland, R. J., Differential neurogenesis in the adult rat dentate gyrus: an identifiable zone that consistently lacks neurogenesis. Eur. J. Neurosci., 25, 1023–1029 (2007).

    Article  PubMed  Google Scholar 

  • Ming, G. L. and Song, H., Adult neurogenesis in the mammalian central nervous system. Annu. Rev. Neurosci., 28, 223–250 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Montaron, M. F., Petry, K. G., Rodriguez, J. J., Marinelli, M., Aurousseau, C., Rougon, G., Le Moal, M., and Abrous, D. N., Adrenalectomy increases neurogenesis but not PSANCAM expression in aged dentate gyrus. Eur. J. Neurosci., 11, 1479–1485 (1999).

    Article  CAS  PubMed  Google Scholar 

  • Montaron, M. F., Piazza, P. V., Aurousseau, C., Urani, A., Le Moal, M., and Abrous, D. N., Implication of corticosteroid receptors in the regulation of hippocampal structural plasticity. Eur. J. Neurosci., 18, 3105–3111 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Nacher, J., Alonso-Llosa, G., Rosell, D. R., and McEwen, B. S., NMDA receptor antagonist treatment increases the production of new neurons in the aged rat hippocampus. Neurobiol. Aging, 24, 273–284 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Nakagawa, S., Kim, J. E., Lee, R., Chen, J., Fujioka, T., Malberg, J., Tsuji, S., and Duman, R. S., Localization of phosphorylated cAMP response element-binding protein in immature neurons of adult hippocampus. J. Neurosci., 22, 9868–9876 (2002).

    CAS  PubMed  Google Scholar 

  • Nakatomi, H., Kuriu, T., Okabe, S., Yamamoto, S., Hatano, O., Kawahara, N., Tamura, A., Kirino, T., and Nakafuku, M., Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors. Cell, 110, 429–441 (2002).

    Article  CAS  PubMed  Google Scholar 

  • Newton, S. S. and Duman, R. S., Neurogenic actions of atypical antipsychotic drugs and therapeutic implications. CNS Drugs, 21, 715–725 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Nixon, K. and Crews, F. T., Binge ethanol exposure decreases neurogenesis in adult rat hippocampus. J. Neurochem., 83, 1087–1093 (2002).

    Article  CAS  PubMed  Google Scholar 

  • Nixon, K. and Crews, F. T., Temporally specific burst in cell proliferation increases hippocampal neurogenesis in pro tracted abstinence from alcohol. J. Neurosci., 24, 9714–9722 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Noonan, M. A., Choi, K. H., Self, D. W., and Eisch, A. J., Withdrawal from cocaine self-administration normalizes deficits in proliferation and enhances maturity of adult-generated hippocampal neurons. J. Neurosci., 28, 2516–2526 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Noonan, M. A., Bulin, S. E., Fuller, D. C., and Eisch, A. J., Reduction of adult hippocampal neurogenesis confers vulnerability in an animal model of cocaine addiction. J. Neurosci., 30, 304–315 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Ormerod, B. K., Lee, T. T., and Galea, L. A., Estradiol initially enhances but subsequently suppresses (via adrenal steroids) granule cell proliferation in the dentate gyrus of adult female rats. J. Neurobiol., 55, 247–260 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Ormerod, B. K., Lee, T. T., and Galea, L. A., Estradiol enhances neurogenesis in the dentate gyri of adult male meadow voles by increasing the survival of young granule neurons. Neuroscience, 128, 645–654 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Osredkar, D., Sall, J. W., Bickler, P. E., and Ferriero, D. M., Erythropoietin promotes hippocampal neurogenesis in in vitro models of neonatal stroke. Neurobiol. Dis., 38, 259–265 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Parent, J. M., Yu, T. W., Leibowitz, R. T., Geschwind, D. H., Sloviter, R. S., and Lowenstein, D. H., Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J. Neurosci., 17, 3727–3738 (1997).

    CAS  PubMed  Google Scholar 

  • Parent, J. M., Janumpalli, S., McNamara, J. O., and Lowenstein, D. H., Increased dentate granule cell neurogenesis following amygdala kindling in the adult rat. Neurosci. Lett., 247, 9–12 (1998).

    Article  CAS  PubMed  Google Scholar 

  • Pathania, M., Yan, L. D., and Bordey, A., A symphony of signals conducts early and late stages of adult neurogenesis. Neuropharmacology, 58, 865–876 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Perez-Martin, M., Cifuentes, M., Grondona, J. M., Lopez-Avalos, M. D., Gomez-Pinedo, U., Garcia-Verdugo, J. M., and Fernandez-Llebrez, P., IGF-I stimulates neurogenesis in the hypothalamus of adult rats. Eur. J. Neurosci., 31, 1533–1548 (2010).

    CAS  PubMed  Google Scholar 

  • Petrus, D. S., Fabel, K., Kronenberg, G., Winter, C., Steiner, B., and Kempermann, G., NMDA and benzodiazepine receptors have synergistic and antagonistic effects on precursor cells in adult hippocampal neurogenesis. Eur. J. Neurosci., 29, 244–252 (2009).

    Article  PubMed  Google Scholar 

  • Ransome, M. I. and Turnley, A. M., Systemically delivered Erythropoietin transiently enhances adult hippocampal neurogenesis. J. Neurochem., 102, 1953–1965 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Reif, A., Fritzen, S., Finger, M., Strobel, A., Lauer, M., Schmitt, A., and Lesch, K. P., Neural stem cell proliferation is decreased in schizophrenia, but not in depression. Mol. Psychiatry, 11, 514–522 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Reynolds, B. A. and Weiss, S., Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science, 255, 1707–1710 (1992).

    Article  CAS  PubMed  Google Scholar 

  • Rice, A. C., Bullock, M. R., and Shelton, K. L., Chronic ethanol consumption transiently reduces adult neural progenitor cell proliferation. Brain Res., 1011, 94–98 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Richards, L. J., Kilpatrick, T. J., and Bartlett, P. F., De novo generation of neuronal cells from the adult mouse brain. Proc. Natl. Acad. Sci. U. S. A., 89, 8591–8595 (1992).

    Article  CAS  PubMed  Google Scholar 

  • Scharfman, H. E., Goodman, J. H., and Sollas, A. L., Granulelike neurons at the hilar/CA3 border after status epilepticus and their synchrony with area CA3 pyramidal cells: functional implications of seizure-induced neurogenesis. J. Neurosci., 20, 6144–6158 (2000).

    CAS  PubMed  Google Scholar 

  • Schmidt, W. and Reymann, K. G., Proliferating cells differentiate into neurons in the hippocampal CA1 region of gerbils after global cerebral ischemia. Neurosci. Lett., 334, 153–156 (2002).

    Article  CAS  PubMed  Google Scholar 

  • Shingo, A. S. and Kito, S., Effects of nicotine on neurogenesis and plasticity of hippocampal neurons. J. Neural Transm., 112, 1475–1478 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Spritzer, M. D. and Galea, L. A., Testosterone and dihydro-testosterone, but not estradiol, enhance survival of new hippocampal neurons in adult male rats. Dev. Neurobiol., 67, 1321–1333 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Sun, D., McGinn, M. J., Zhou, Z., Harvey, H. B., Bullock, M. R., and Colello, R. J., Anatomical integration of newly generated dentate granule neurons following traumatic brain injury in adult rats and its association to cognitive recovery. Exp. Neurol., 204, 264–272 (2007).

    Article  PubMed  Google Scholar 

  • Takagi, Y., Nozaki, K., Takahashi, J., Yodoi, J., Ishikawa, M., and Hashimoto, N., Proliferation of neuronal precursor cells in the dentate gyrus is accelerated after transient forebrain ischemia in mice. Brain Res., 831, 283–287 (1999).

    Article  CAS  PubMed  Google Scholar 

  • Takasawa, K., Kitagawa, K., Yagita, Y., Sasaki, T., Tanaka, S., Matsushita, K., Ohstuki, T., Miyata, T., Okano, H., Hori, M., and Matsumoto, M., Increased proliferation of neural progenitor cells but reduced survival of newborn cells in the contralateral hippocampus after focal cerebral ischemia in rats. J. Cereb. Blood Flow Metab., 22, 299–307 (2002).

    Article  PubMed  Google Scholar 

  • Tanapat, P., Hastings, N. B., Reeves, A. J., and Gould, E., Estrogen stimulates a transient increase in the number of new neurons in the dentate gyrus of the adult female rat. J. Neurosci., 19, 5792–5801 (1999).

    CAS  PubMed  Google Scholar 

  • Tashiro, A., Sandler, V. M., Toni, N., Zhao, C., and Gage, F. H., NMDA-receptor-mediated, cell-specific integration of new neurons in adult dentate gyrus. Nature, 442, 929–933 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Teuchert-Noodt, G., Dawirs, R. R., and Hildebrandt, K., Adult treatment with methamphetamine transiently decreases dentate granule cell proliferation in the gerbil hippocampus. J. Neural Transm., 107, 133–143 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Tonchev, A. B., Yamashima, T., Zhao, L., Okano, H. J., and Okano, H., Proliferation of neural and neuronal progenitors after global brain ischemia in young adult macaque monkeys. Mol. Cell. Neurosci., 23, 292–301 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Tozuka, Y., Fukuda, S., Namba, T., Seki, T., and Hisatsune, T., GABAergic excitation promotes neuronal differentiation in adult hippocampal progenitor cells. Neuron, 47, 803–815 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Trejo, J. L., Carro, E., and Torres-Aleman, I., Circulating insulin-like growth factor I mediates exercise-induced increases in the number of new neurons in the adult hippocampus. J. Neurosci., 21, 1628–1634 (2001).

    CAS  PubMed  Google Scholar 

  • Tureyen, K., Vemuganti, R., Sailor, K. A., Bowen, K. K., and Dempsey, R. J., Transient focal cerebral ischemia-induced neurogenesis in the dentate gyrus of the adult mouse. J. Neurosurg., 101, 799–805 (2004).

    Article  PubMed  Google Scholar 

  • Van Eekelen, J. A., Jiang, W., De Kloet, E. R., and Bohn, M. C., Distribution of the mineralocorticoid and the glucocorticoid receptor mRNAs in the rat hippocampus. J. Neurosci. Res., 21, 88–94 (1988).

    Article  PubMed  Google Scholar 

  • Van Praag, H., Kempermann, G., and Gage, F. H., Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat. Neurosci., 2, 266–270 (1999).

    Article  PubMed  Google Scholar 

  • Verret, L., Jankowsky, J. L., Xu, G. M., Borchelt, D. R., and Rampon, C., Alzheimer’s-type amyloidosis in transgenic mice impairs survival of newborn neurons derived from adult hippocampal neurogenesis. J. Neurosci., 27, 6771–6780 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Vessal, M. and Darian-Smith, C., Adult neurogenesis occurs in primate sensorimotor cortex following cervical dorsal rhizotomy. J. Neurosci., 30, 8613–8623 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Wakade, C. G., Mahadik, S. P., Waller, J. L., and Chiu, F. C., Atypical neuroleptics stimulate neurogenesis in adult rat brain. J. Neurosci. Res., 69, 72–79 (2002).

    Article  CAS  PubMed  Google Scholar 

  • Wang, J. W., David, D. J., Monckton, J. E., Battaglia, F., and Hen, R., Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells. J. Neurosci., 28, 1374–1384 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Wang, L., Zhang, Z., Wang, Y., Zhang, R., and Chopp, M., Treatment of stroke with erythropoietin enhances neurogenesis and angiogenesis and improves neurological function in rats. Stroke, 35, 1732–1737 (2004a).

    Article  CAS  PubMed  Google Scholar 

  • Wang, R., Dineley, K. T., Sweatt, J. D., and Zheng, H., Presenilin 1 familial Alzheimer’s disease mutation leads to defective associative learning and impaired adult neurogenesis. Neuroscience, 126, 305–312 (2004b).

    Article  CAS  PubMed  Google Scholar 

  • Wen, P. H., Shao, X., Shao, Z., Hof, P. R., Wisniewski, T., Kelley, K., Friedrich, V. L., Jr., Ho, L., Pasinetti, G. M., Shioi, J., Robakis, N. K., and Elder, G. A., Overexpression of wild type but not an FAD mutant presenilin-1 promotes neurogenesis in the hippocampus of adult mice. Neurobiol. Dis., 10, 8–19 (2002).

    Article  CAS  PubMed  Google Scholar 

  • Wen, P. H., Hof, P. R., Chen, X., Gluck, K., Austin, G., Younkin, S. G., Younkin, L. H., DeGasperi, R., Gama Sosa, M. A., Robakis, N. K., Haroutunian, V., and Elder, G. A., The presenilin-1 familial Alzheimer disease mutant P117L impairs neurogenesis in the hippocampus of adult mice. Exp. Neurol., 188, 224–237 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Wong, E. Y. and Herbert, J., Roles of mineralocorticoid and glucocorticoid receptors in the regulation of progenitor proliferation in the adult hippocampus. Eur. J. Neurosci., 22, 785–792 (2005).

    Article  PubMed  Google Scholar 

  • Wong, E. Y. and Herbert, J., Raised circulating corticosterone inhibits neuronal differentiation of progenitor cells in the adult hippocampus. Neuroscience, 137, 83–92 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Xiong, Y., Mahmood, A., Lu, D., Qu, C., Kazmi, H., Goussev, A., Zhang, Z. G., Noguchi, C. T., Schallert, T., and Chopp, M., Histological and functional outcomes after traumatic brain injury in mice null for the erythropoietin receptor in the central nervous system. Brain Res., 1230, 247–257 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Yagita, Y., Kitagawa, K., Ohtsuki, T., Takasawa, K., Miyata, T., Okano, H., Hori, M., and Matsumoto, M., Neurogenesis by progenitor cells in the ischemic adult rat hippocampus. Stroke, 32, 1890–1896 (2001).

    CAS  PubMed  Google Scholar 

  • Yamaguchi, M., Suzuki, T., Seki, T., Namba, T., Juan, R., Arai, H., Hori, T., and Asada, T., Repetitive cocaine administration decreases neurogenesis in adult rat hippocampus. Ann. N. Y. Acad. Sci., 1025, 351–362 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Yoshimura, S., Takagi, Y., Harada, J., Teramoto, T., Thomas, S. S., Waeber, C., Bakowska, J. C., Breakefield, X. O., and Moskowitz, M. A., FGF-2 regulation of neurogenesis in adult hippocampus after brain injury. Proc. Natl. Acad. Sci. U. S. A., 98, 5874–5879 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Zhang, C., McNeil, E., Dressler, L., and Siman, R., Longlasting impairment in hippocampal neurogenesis associated with amyloid deposition in a knock-in mouse model of familial Alzheimer’s disease. Exp. Neurol., 204, 77–87 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Zhang, Y., Allodi, S., Sandeman, D. C., and Beltz, B. S., Adult neurogenesis in the crayfish brain: proliferation, migration, and possible origin of precursor cells. Dev. Neurobiol., 69, 415–436 (2009).

    Article  PubMed  Google Scholar 

  • Zhao, C., Deng, W., and Gage, F. H., Mechanisms and functional implications of adult neurogenesis. Cell, 132, 645–660 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Zhao, M., Momma, S., Delfani, K., Carlen, M., Cassidy, R. M., Johansson, C. B., Brismar, H., Shupliakov, O., Frisen, J., and Janson, A. M., Evidence for neurogenesis in the adult mammalian substantia nigra. Proc. Natl. Acad. Sci. U. S. A., 100, 7925–7930 (2003).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Seong Yun Kim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cho, KO., Kim, S.Y. Effects of brain insults and pharmacological manipulations on the adult hippocampal neurogenesis. Arch. Pharm. Res. 33, 1475–1488 (2010). https://doi.org/10.1007/s12272-010-1002-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-010-1002-y

Key words

Navigation