Skip to main content
Log in

Postnatal Development of Neurons, Interneurons and Glial Cells in the Substantia Nigra of Mice

  • Original Research
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

We investigated postnatal alterations of neurons, interneurons and glial cells in the mouse substantia nigra using immunohistochemistry. Tyrosine hydroxylase (TH), neuronal nuclei (NeuN), parvalbumin (PV), neuronal nitric oxide synthase (nNOS), glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (Iba 1), CNPase (2′,3′-cyclic nucleotide 3′-phosphodiesterase), brain-derived neurotrophic factor (BDNF) and glial cell-line-derived neurotrophic factor (GDNF) immunoreactivity were measured in 1-, 2-, 4- and 8-week-old mice. In the present study, the maturation of NeuN-immunopositive neurons preceded the production of TH in the substantia nigra during postnatal development in mice. Furthermore, the maturation of nNOS-immunopositive interneurons preceded the maturation of PV-immunopositive interneurons in the substantia nigra during postnatal development. Among astrocytes, microglia and oligodendrocytes, in contrast, the development process of oligodendrocytes is delayed in the substantia nigra. Our double-labeled immunohistochemical study suggests that the neurotrophic factors such as BDNF and GDNF secreted by GFAP-positive astrocytes may play some role in maturation of neurons, interneurons and glial cells of the substantia nigra during postnatal development in mice. Thus, our findings provide valuable information on the development processes of the substantia nigra.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13

Similar content being viewed by others

References

  • Akerud P, Canals JM, Snyder EY, Arenas E (2001) Neuroprotection through delivery of glial cell line-derived neurotrophic factor by neural stem cells in a mouse model of Parkinson’s disease. J Neurosci 21:8108–8118

    CAS  PubMed  Google Scholar 

  • Baquet ZC, Bickford PC, Jones KR (2005) Brain-derived neurotrophic factor is required for the establishment of the proper number of dopaminergic neurons in the substantia nigra pars compacta. J Neurosci 25:6251–6259

    Article  CAS  PubMed  Google Scholar 

  • Celio MR (1986) Parvalbumin in most gamma-aminobutyric acid-containing neurons of the rat cerebral cortex. Science 231:995–997

    Article  CAS  PubMed  Google Scholar 

  • Cowan RL, Wilson CJ, Emson PC, Heizmann CW (1990) Parvalbumin-containing GABAergic interneurons in the rat neostriatum. J Comp Neurol 302:197–205

    Article  CAS  PubMed  Google Scholar 

  • Dalmau I, Finsen B, Zimmer J, Gonzalez B, Castellano B (1998) Development of microglia in the postnatal rat hippocampus. Hippocampus 8:458–474

    Article  CAS  PubMed  Google Scholar 

  • Dawson TM, Bredt DS, Fotuhi M, Hwang PM, Snyder SH (1991) Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues. Proc Natl Acad Sci USA 88:7797–7801

    Article  CAS  PubMed  Google Scholar 

  • Diamond JS, Jahr CE (1997) Transporters buffer synaptically released glutamate on a submillisecond time scale. J Neurosci 17:4672–4687

    CAS  PubMed  Google Scholar 

  • Elkabes S, DiCicco-Bloom EM, Black IB (1996) Brain microglia/macrophages express neurotrophins that selectively regulate microglial proliferation and function. J Neurosci 16:2508–2521

    CAS  PubMed  Google Scholar 

  • Feng L, Wang CY, Jiang H, Oho C, Mizuno K, Dugich-Djordjevic M, Lu B (1999) Differential effects of GDNF and BDNF on cultured ventral mesencephalic neurons. Brain Res Mol Brain Res 66:62–70

    Article  CAS  PubMed  Google Scholar 

  • Floresco SB, West AR, Ash B, Moore H, Grace AA (2003) Afferent modulation of dopamine neuron firing differentially regulates tonic and phasic dopamine transmission. Nat Neurosci 6:968–973

    Article  CAS  PubMed  Google Scholar 

  • Gash DM, Zhang Z, Ovadia A, Cass WA, Yi A, Simmerman L, Russell D, Martin D, Lapchak PA, Collins F, Hoffer BJ, Gerhardt GA (1996) Functional recovery in parkinsonian monkeys treated with GDNF. Nature 380:252–255

    Article  CAS  PubMed  Google Scholar 

  • Grace AA (1991) Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neuroscience 41:1–24

    Article  CAS  PubMed  Google Scholar 

  • Graveland GA, DiFiglia M (1985) The frequency and distribution of medium-sized neurons with indented nuclei in the primate and rodent neostriatum. Brain Res 327:307–311

    Article  CAS  PubMed  Google Scholar 

  • Hayakawa N, Kato H, Araki T (2007) Age-related changes of astrocytes, oligodendrocytes and microglia in the mouse hippocampal CA1 sector. Mech Ageing Dev 128:311–316

    Article  CAS  PubMed  Google Scholar 

  • Himeda T, Hayakawa N, Tounai H, Sakuma M, Kato H, Araki T (2005) Alterations of interneurons of the gerbil hippocampus after transient cerebral ischemia: effect of pitavastatin. Neuropsychopharmacology 30:2014–2025

    Article  CAS  PubMed  Google Scholar 

  • Himeda T, Watanabe Y, Tounai H, Hayakawa N, Kato H, Araki T (2006) Time dependent alterations of co-localization of S100β and GFAP in the MPTP-treated mice. J Neural Transm 113:1887–1894

    Article  CAS  PubMed  Google Scholar 

  • Himeda T, Tounai H, Hayakawa N, Araki T (2007) Postischemic alterations of BDNF, NGF, HSP 70 and ubiquitin immunoreactivity in the gerbil hippocampus: pharmacological approach. Cell Mol Neurobiol 27:229–250

    Article  CAS  PubMed  Google Scholar 

  • Hyman C, Hofer M, Barde YA, Juhasz M, Yancopoulos GD, Squinto SP, Lindsay RM (1991) BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature 350:230–232

    Article  CAS  PubMed  Google Scholar 

  • Jarskog LF, Miyamoto S, Lieberman JA (2007) Schizophrenia: new pathological insights and therapies. Annu Rev Med 58:49–61

    Article  CAS  PubMed  Google Scholar 

  • Katoh-Semba R, Tsuzuki M, Miyazaki N, Yoshida A, Nakajima H, Nakagawa C, Kitajima S, Matsuda M (2007) Distribution and immunohistochemical localization of GDNF protein in selected neural and non-neural tissues of rats during development and changes in unilateral 6-hydroxydopamine lesions. Neurosci Res 59:277–287

    Article  CAS  PubMed  Google Scholar 

  • Kauer JA, Malenka RC (2007) Synaptic plasticity and addiction. Nat Rev Neurosci 8:844–858

    Article  CAS  PubMed  Google Scholar 

  • Kawaguchi Y, Wilson CJ, Augood SJ, Emson PC (1995) Striatal interneurons: chemical, physiological and morphological characterization. Tends Neurosci 18:527–535

    Article  CAS  Google Scholar 

  • Kempermann G, Neumann H (2003) Neuroscience. Microglia: the enemy within? Science 302:1760–1765

    Article  Google Scholar 

  • Kimelberg HK, Norenberg MD (1989) Astrocytes. Sci Am 260:66–72

    Article  CAS  PubMed  Google Scholar 

  • Lambert WS, Clark AF, Wordinger RJ (2004) Effect of exogenous neurotrophins on Trk receptor phosphorylation, cell proliferation, and neurotrophin secretion by cells isolated from the human lamina cribrosa. Mol Vis 10:289–296

    CAS  PubMed  Google Scholar 

  • Lee VM, Goedert M, Trojanowski JQ (2001) Neurodegenerative tauopathies. Annu Rev Neurosci 24:1121–1159

    Article  CAS  PubMed  Google Scholar 

  • Liesi P, Silver J (1988) Is astrocyte laminin involved in axon guidance in the mammalian CNS? Dev Biol 130:774–785

    Article  CAS  PubMed  Google Scholar 

  • Lin L-FH, Doherty DH, Lile JD, Bektesh S, Collins F (1993) GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 260:1130–1132

    Article  CAS  PubMed  Google Scholar 

  • McGeer PL, McGeer EG (2008) Glial reactions in Parkinson’s disease. Mov Disord 23:474–483

    Article  PubMed  Google Scholar 

  • McTigue DM, Horner PJ, Stokes BT, Gage FH (1998) Neurotrophin-3 and brain-derived neurotrophic factor induce oligodendrocyte proliferation and myelination of regenerating axons in the contused adult rat spinal cord. J Neurosci 18:5354–5365

    CAS  PubMed  Google Scholar 

  • Meshul CK, Seil FJ, Herndon RM (1987) Astrocytes play a role in regulation of synaptic density. Brain Res 402:139–145

    Article  CAS  PubMed  Google Scholar 

  • Miller FD, Kaplan DR (2001) Neurotrophin signalling pathways regulating neuronal apoptosis. Cell Mol Life Sci 58:1045–1053

    Article  CAS  PubMed  Google Scholar 

  • Morton GJ, Cummings DE, Baskin DG, Barsh GS, Schwartz MW (2006) Central nervous system control of food intake and body weight. Nature 443:289–295

    Article  CAS  PubMed  Google Scholar 

  • Pochon NA, Menoud A, Tseng JL, Zurn AD, Aebischer P (1997) Neuronal GDNF expression in the adult rat nervous system identified by in situ hybridization. Eur J Neurosci 9:463–471

    Article  CAS  PubMed  Google Scholar 

  • Redgrave P, Prescott TJ, Gurney K (1999) The basal ganglia: a vertebrate solution to the selection problem? Neuroscience 89:1009–1023

    Article  CAS  PubMed  Google Scholar 

  • Rudge JS, Smith GM, Silver J (1989) An in vitro model of wound healing CNS: analysis of cell reaction and interaction at different ages. Exp Neurol 103:1–16

    Article  CAS  PubMed  Google Scholar 

  • Sakuma M, Hyakawa N, Kato H, Araki T (2008) Time dependent changes of striatal interneurons after focal cerebral ischemia in rats. J Neural Transm 115:413–422

    Article  CAS  PubMed  Google Scholar 

  • Schultz W (1998) Predictive reward signal of dopamine neurons. J Neurophysiol 80:1–27

    CAS  PubMed  Google Scholar 

  • Schwartz-Bloom RD, Sah R (2001) gamma-Aminobutyric acid(A) neurotransmission and cerebral ischemia. J Neurochem 77:353–371

    Article  CAS  PubMed  Google Scholar 

  • Seroogy KB, Lundgren KH, Tran TM, Guthrie KM, Isackson PJ, Gall CM (1994) Dopaminergic neurons in rat ventral midbrain express brain-derived neurotrophic factor and neurotrophin-3 mRNAs. J Comp Neurol 342:321–334

    Article  CAS  PubMed  Google Scholar 

  • Streit WJ, Mrak RE, Griffin WS (2004) Microglia and neuroinflammation: a pathological perspective. J Neuroinflammation 1:14

    Article  PubMed  Google Scholar 

  • Takagi S, Hayakawa N, Kimoto H, Kato H, Araki T (2007) Damage to oligodendrocytes in the striatum after MPTP neurotoxicity in mice. J Neural Transm 114:1553–1557

    Article  CAS  PubMed  Google Scholar 

  • Tomac A, Lindqvist E, Lin LF, Ogren SO, Young D, Hoffer BJ, Olson L (1995) Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo. Nature 373:335–339

    Article  CAS  PubMed  Google Scholar 

  • Vivier E, Malissen B (2005) Innate and adaptive immunity: specificities and signaling hierarchies revisited. Nat Immunol 6:17–21

    Article  CAS  PubMed  Google Scholar 

  • Zhang J, Geula C, Lu C, Koziel H, Hatcher LM, Roisen FJ (2003) Neurotrophins regulate proliferation and survival of two microglial cell lines in vitro. Exp Neurol 183:469–481

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tsutomu Araki.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Abe, M., Kimoto, H., Eto, R. et al. Postnatal Development of Neurons, Interneurons and Glial Cells in the Substantia Nigra of Mice. Cell Mol Neurobiol 30, 917–928 (2010). https://doi.org/10.1007/s10571-010-9521-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-010-9521-0

Keywords

Navigation