Abstract
Neurogenesis continues to occur in the mature rodent brain with one of the most prominent sources for new neurons being the subgranular layer (SGL) of the dentate gyrus (DG) in the hippocampus. A number of factors can stimulate this process including synaptic activity and injury. To determine if this process would occur upon a direct injury to the dentate region, we exposed young, 21 day old male CD-1 mice to the hippocampal toxicant, trimethyltin (TMT). An acute i.p. injection of TMT (2 mg/kg) produced extensive damage and loss of dentate granule neurons within 72 h. This active period of degeneration was accompanied by an increase in the generation of progenitor cells within the SGL as identified by BrdU uptake and Ki-67 immunostaining. As additional markers for neurogenesis, both nestin and doublecortin showed increased staining patterns within the blades of the dentate. In these young weanling mice, the level of proliferation was sufficient to significantly repopulate the dentate region by 4 weeks post-TMT, suggesting a high level of regenerative potential. Our data indicate a significant level of neurogenesis occurring during the active process of degeneration and in an environment of microglia activation. The TMT-induced injury offers a model system for further examination of the process of neurogenesis, neural adaptation, and the influence of inflammatory factors and glia interactions.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Bruccoleri A and GJ Harry (2000) Chemicla-induced hippocampal neurodegeneration and elevations in TNFalpha, TNFbeta, IL-1alpha, IP-10, and MCP-1 mRNA in osteopetrotic (op/op) mice.J. Neurosci. Res. 62, 146–155.
Bruccoleri A, H Brown and GJ Harry (1998) Cellular localization and temporal elevation of tumor necrosis factor-alpha, interleukin-1 alpha, and transforming growth factor-beta mRNA in hippocampal injury response induced by trimethyltin.J. Neurochem. 71, 1577–1587.
Cameron HA and RD McKay (2001) Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus.J. Comp. Neurol. 435, 406–417.
Covolan L, LT Riberiro, BM Longo and LE Mello (2000) Cell damage and neurogenesis in the dentate granule cell layer of adult rats after pilocarpine-or kainate-induced status epilepticus.Hippocampus 10, 169–180.
Eskes C, L Juillerat-Jeanneret, G Leuba, P Honegger and F Monnet-Tschudi (2003) Involvement of microglia-neuron interactions in the tumor necrosis factor-alpha release, microglial activation, and neurodegeneration induced by trimethyltin.J. Neurosci. Res. 71, 583–590.
Fiedorowicz A, I Figiel, B Kaminska, M Zaremba, S Wilk, B Oderfeld-Nowak (2001) Dentate granule neuron apoptosis and glia activation in murine hippocampus induced by trimethyltin exposure.Brain Res. 912, 116–127.
Freeman RS, S Estus and EM Johnson Jr (1994) Analysis of cell cycle-related gene expression in postmitotic neurons: selective induction of cyclin D1 during programmed cell death.Neuron 12, 343–355.
Gage FH (2002) Neurogenesis in the adult brain.J. Neurosci. 22, 612–613.
Geloso M, A Vercelli, V Corvino, M Repici, M. Boca, Z Haglid, G Zelano and F Michetti (2002) Cyclooxygenase-2 and caspase 3 expression in trimethyltin-induced apoptosis in the mouse hippocampus.Exp. Neurol. 175, 152–160.
Harry GJ and C Lefebvre d'Hellencourt (2003) The neuroinflammatory components of the trimethyltin (TMT) model of hippocampal neurodegeneration, In:Neuroinflammation, 2nd Edition, Mechanisms and Management, Wood PL, Ed. (Humana Press, Totowa, NJ, USA), pp 301–329.
Jin K, M Minami, JQ Lan, XO Mao, S Batteur, RP Simon and DA Greenberg (2001) Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat.Proc. Natl. Acad. Sci. USA 98, 4710–4715.
Kee N, S Sivalingam, R Boonstra and JM Wojtowicz (2002) The utility of Ki-67 and BrdU as proliferative markers of adult neurogenesis.J. Neurosci. Meth. 115, 97–105.
Kempermann G, D Gast, G Kronenberg, M Yamaguchi and FH Gage (2003) Early determination and long-term persistence of adult-generated new neurons in the hippocampus of mice.Development 130, 391–399.
Kennea NL and H Mehmet (2002) Neural stem cells.J. Pathol. 197, 536–550.
Markakis EA and FH Gage (1999) Adult-generated neurons in the dentate gyrus send axonal projections to field CA3 and are surrounded by synaptic vesicles.J. Comp. Neurol. 406, 449–460.
McPherson CA, J Kubik, RN Wine, C Lefebvre d'Hellencourt and GJ Harry (2003) Alterations in cyclin A, B, and D1 in mouse dentate gyrus following TMT-induced hippocampal damage.Neurotoxicity Res. 5, 339–354.
Padmanabhan J, DS Park, LA Greene and ML Shelanski (1999) Role of cell cycle regulatory proteins in cerebellar granule neuron apoptosis.J. Neurosci. 19, 8747–8756.
Parent JM and DH Lowenstein (2002) Seizure-induced neurogenesis: are more new neurons good for an adult brain?.Prog. Brain Res. 135, 121–131.
Reuhl KR, EA Smallridge, LW Chang and BA Mackenzie (1983) Devleopmental effects of trimethyltin intoxication in the neonatal mouse. I. Light microscopic studies.Neurotoxicology 4, 19–28.
Streit WJ, SD Hurley, TS McGraw and SL Semple-Rowland (2000) Comparative evaluation of cytokine profiles and reactive gliosis supports a critical role for interleukin-6 in neuron-glia signaling during regeneration.J. Neurosci. Res. 61, 10–20.
Takagi Y, K Nozaki, J Takahashi, J Yodoi, M Ishikawa and N Hashimoto (1999) Proliferation of neuronal precursor cells in the dentate gyrus is accelerated after transient forebrain ischemia in mice.Brain Res. 831, 283–287.
van Praag H, AF Schinder, BR Christie, N Toni, TD Palmer and FH Gage (2002) Functional neurogenesis in the adult hippocampus.Nature 415, 1030–1034.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Harry, G.J., McPherson, C.A., Wine, R.N. et al. Trimethyltin-induced neurogenesis in the murine hippocampus. neurotox res 5, 623–627 (2003). https://doi.org/10.1007/BF03033182
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF03033182