Skip to main content
PMC home page
Neuroscience Bulletin logoLink to Neuroscience Bulletin
. 2007 Dec 15;23(1):46–52. doi: 10.1007/s12264-007-0007-0

Changes of cell proliferation and differentiation in the developing brain of mouse

小鼠脑组织发育期细增生与分化的改变

Lin Qiu 1,✉, Chang-Lian Zhu 2, Xiao-Yang Wang 2, Fa-Lin Xu 2
PMCID: PMC5550568  PMID: 17592525

Abstract

Objective

To investigate the cell proliferation and differentiation in the developing brain of mouse.

Methods

C57/BL6 mice were divided into 3 groups at random. Bromodeoxyuridine (BrdU) was injected into the brains in different development periods once a day for 7 d. The brains were retrieved 4 weeks after the last BrdU injection. Immunohistochemical and immunofluorescent studies were carried out for detecting cell proliferation (BrdU) and cell differentiation (NeuN, APC, Iba1, and S100β), respectively.

Results

The number of BrdU labeled cells decreased significantly with the development of the brain. Cell proliferation was prominent in the cortex and striatum. A small portion of BrdU and NeuN double labeled cells could be detected in the cortex at the early stage of development, and in the striatum and CA of the hippocampus in all groups. The majority of BrdU labeled cells were neuroglia, and the number of neuroglia cells decreased dramatically with brain maturation. Neurogenesis is the major cytogenesis in the dentate gyrus.

Conclusion

These results demonstrated that cell proliferation, differentiation and survival were age and brain region related.

Keywords: brain development, neurogenesis, gliogenesis

References

  • [1].Barnea A., Nottebohm F. Seasonal recruitment of hippocampal neurons in adult free-ranging black-capped chickadees. Proc Natl Acad Sci USA. 1994;91:11217–11221. doi: 10.1073/pnas.91.23.11217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [2].Gould E., Beylin A., Tanapat P., Reeves A., Shors T.J. Learning enhances adult neurogenesis in the hippocampal formation. Nat Neurosci. 1999;2:260–265. doi: 10.1038/6365. [DOI] [PubMed] [Google Scholar]
  • [3].Kempermann G., Kuhn H.G., Gage F.H. More hippocampal neurons in adult mice living in an enriched environment. Nature. 1997;386:493–495. doi: 10.1038/386493a0. [DOI] [PubMed] [Google Scholar]
  • [4].van Praag H., van Praag H., Christie B.R., Sejnowski T.J., Gage F.H. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci USA. 1999;96:13427–13431. doi: 10.1073/pnas.96.23.13427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [5].van Praag H., Kempermann G., Gage F.H. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci. 1999;2:266–270. doi: 10.1038/6368. [DOI] [PubMed] [Google Scholar]
  • [6].Gould E., Tanapat P., McEwen B.S., Flugge G., Fuchs E. Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress. Proc Natl Acad Sci USA. 1998;95:3168–3171. doi: 10.1073/pnas.95.6.3168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [7].Eriksson P.S., Perfilieva E., Bjork-Eriksson T., Alborn A.M., Nordborg C., Peterson D.A., et al. Neurogenesis in the adult human hippocampus. Nat Med. 1998;4:1313–1317. doi: 10.1038/3305. [DOI] [PubMed] [Google Scholar]
  • [8].Kuhn H.G., Dickinson-Anson H., Gage F.H. Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci. 1996;16:2027–2033. doi: 10.1523/JNEUROSCI.16-06-02027.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [9].Sun D., Colello R.J., Daugherty W.P., Kwon T.H., McGinn M.J., Harvey H.B., et al. Cell proliferation and neuronal differentiation in the dentate gyrus in juvenile and adult rats following traumatic brain injury. J Neurotrauma. 2005;22:95–105. doi: 10.1089/neu.2005.22.95. [DOI] [PubMed] [Google Scholar]
  • [10].Enwere E., Shingo T., Gregg C., Fujikawa H., Ohta S., Weiss S. Aging results in reduced epidermal growth factor receptor signaling, diminished olfactory neurogenesis, and deficits in fine olfactory discrimination. J Neurosci. 2004;24:8354–8365. doi: 10.1523/JNEUROSCI.2751-04.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [11].Komitova M., Perfilieva E., Mattsson B., Eriksson P.S., Johansson B.B. Enriched environment after focal cortical ischemia enhances the generation of astroglia and NG2 positive polydendrocytes in adult rat neocortex. Exp Neurol. 2006;199:113–121. doi: 10.1016/j.expneurol.2005.12.007. [DOI] [PubMed] [Google Scholar]
  • [12].Larsson E., Lindvall O., Kokaia Z. Stereological assessment of vulnerability of immunocytochemically identified striatal and hippocampal neurons after global cerebral ischemia in rats. Brain Res. 2001;913:117–132. doi: 10.1016/S0006-8993(01)02762-7. [DOI] [PubMed] [Google Scholar]
  • [13].Yoshimura S., Takagi Y., Harada J., Teramoto T., Thomas S.S., Waeber C., et al. FGF-2 regulation of neurogenesis in adult hippocampus after brain injury. Proc Natl Acad Sci USA. 2001;98:5874–5879. doi: 10.1073/pnas.101034998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [14].Matsuoka N., Nozaki K., Takagi Y., Nishimura M., Hayashi J., Miyatake S., et al. Adenovirus-mediated gene transfer of fibroblast growth factor-2 increases BrdU-positive cells after forebrain ischemia in gerbils. Stroke. 2003;34:1519–1525. doi: 10.1161/01.STR.0000070840.56414.3B. [DOI] [PubMed] [Google Scholar]
  • [15].Jin K., Mao X.O., Sun Y., Xie L., Jin L., Nishi E., et al. Heparinbinding epidermal growth factor-like growth factor: hypoxiainducible expression in vitro and stimulation of neurogenesis in vitro and in vivo. J Neurosci. 2002;22:5365–5373. doi: 10.1523/JNEUROSCI.22-13-05365.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [16].Craig C.G., Tropepe V., Morshead C.M., Reynolds B.A., Weiss S., van der Kooy D. In vivo growth factor expansion of endogenous subependymal neural precursor cell populations in the adult mouse brain. J Neurosci. 1996;16:2649–2658. doi: 10.1523/JNEUROSCI.16-08-02649.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [17].Pencea V., Bingaman K.D., Wiegand S.J., Luskin M.B. 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. J Neurosci. 2001;21:6706–6717. doi: 10.1523/JNEUROSCI.21-17-06706.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [18].Tsai P.T., Ohab J.J., Kertesz N., Groszer M., Matter C., Gao J., et al. A critical role of erythropoietin receptor in neurogenesis and post-stroke recovery. J Neurosci. 2006;26:1269–1274. doi: 10.1523/JNEUROSCI.4480-05.2006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [19].Caday C.G., Klagsbrun M., Fanning P.J., Mirzabegian A., Finklestein S.P. Fibroblast growth factor (FGF) levels in the developing rat brain. Brain Res Dev Brain Res. 1990;52:241–246. doi: 10.1016/0165-3806(90)90240-Y. [DOI] [PubMed] [Google Scholar]
  • [20].Plata-Salaman C.R. Epidermal growth factor and the nervous system. Peptides. 1991;12:653–663. doi: 10.1016/0196-9781(91)90115-6. [DOI] [PubMed] [Google Scholar]
  • [21].Gould E., Reeves A.J., Graziano M.S., Gross C.G. Neurogenesis in the neocortex of adult primates. Science. 1999;286:548–552. doi: 10.1126/science.286.5439.548. [DOI] [PubMed] [Google Scholar]
  • [22].Koketsu D., Mikami A., Miyamoto Y., Hisatsune T. Nonrenewal of neurons in the cerebral neocortex of adult macaque monkeys. J Neurosci. 2003;23:937–942. doi: 10.1523/JNEUROSCI.23-03-00937.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [23].Hayashi T., Iwai M., Ikeda T., Jin G., Deguchi K., Nagotani S., et al. Neural precursor cells division and migration in neonatal rat brain after ischemic/hypoxic injury. Brain Res. 2005;1038:41–49. doi: 10.1016/j.brainres.2004.12.048. [DOI] [PubMed] [Google Scholar]
  • [24].Jin K., Sun Y., Xie L., Batteur S., Mao X.O., Smelick C., et al. Neurogenesis and aging: FGF-2 and HB-EGF restore neurogenesis in hippocampus and subventricular zone of aged mice. Aging Cell. 2003;2:175–183. doi: 10.1046/j.1474-9728.2003.00046.x. [DOI] [PubMed] [Google Scholar]
  • [25].Aarum J., Sandberg K., Haeberlein S.L., Persson M.A. Migration and differentiation of neural precursor cells can be directed by microglia. Proc Natl Acad Sci USA. 2003;100:15983–15988. doi: 10.1073/pnas.2237050100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [26].Zaidi A.U., Bessert D.A., Ong J.E., Xu H., Barks J.D., Silverstein F.S., et al. New oligodendrocytes are generated after neonatal hypoxic-ischemic brain injury in rodents. Glia. 2004;46:380–390. doi: 10.1002/glia.20013. [DOI] [PubMed] [Google Scholar]
  • [27].Fields R.D., Stevens-Graham B. New insights into neuron-glia communication. Science. 2002;298:556–562. doi: 10.1126/science.298.5593.556. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Neuroscience Bulletin are provided here courtesy of Springer

RESOURCES