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Expression of GluR6 kainate receptor subunit in granular layer of weaver mouse cerebellum

  • Basic Neurosciences, Genetics and Immunology - Original Article
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Abstract

The Girk2 wv (weaver) mutation impairs migration of cerebellar granule cells from external to internal granular layer and induces neuronal death during the first 2 weeks of postnatal life. Kainate receptors are heteromeric ionotropic receptors of glutamate consisting of five subunits termed GluR5, GluR6, GluR7, KA1 and KA2. In order to investigate whether the weaver gene affects the expression of kainate receptors in weaver cerebellum, we determined mRNA expression levels of GluR6 kainate receptor subunit and [3H]kainic acid specific binding in the developing cerebellum, using in situ hybridization and receptor film autoradiography, respectively. In the weaver postnatal day 10 (P10) cerebellum, our data indicated lower levels of GluR6 mRNA expression and lower [3H]kainic acid specific binding in external granular layer (EGL) compared to normal EGL. Our results are indicative of either down-regulation of kainate receptors or modulation of their functional characteristics in weaver granule cells.

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References

  • Akaneya Y (2007) Activity regulates the expression of AMPA receptor subunit GluR4 in developing visual cortex. Eur J Neurosci 25(6):1641–1646

    Article  PubMed  Google Scholar 

  • Akinsola BE, Randall RS, Karvonen LL, Taylor RE, Liesi P (2001) Involvement of non-NMDA receptors in the rescue of weaver cerebellar granule neurons and sensitivity to ethanol of cerebellar AMPA receptors in oocytes. Mol Brain Res 93:8–17

    Article  Google Scholar 

  • Bahn S, Volk B, Wisden W (1994) Kainate receptor gene expression in the developing rat brain. J Neurosci 14(9):5525–5547

    PubMed  CAS  Google Scholar 

  • Belcher SM, Howe JR (1997) Characterization of RNA editing of the glutamate-receptor subunits GluR5 and GluR6 in granule cells during cerebellar development. Mol Brain Res 52:130–138

    Article  PubMed  CAS  Google Scholar 

  • Bessho Y, Nawa H, Nakanishi S (1994) Selective up-regulation of an NMDA receptor subunit mRNA in cultured cerebellar granule cells by K+–induced depolarization and NMDA treatment. Neuron 12(1):87–95

    Article  PubMed  CAS  Google Scholar 

  • Burnashev N, Zhou Z, Neher E, Sakmann B (1995) Fractional calcium currents through recombinant GluR channels of the NMDA, AMPA and kainate receptor subtypes. J Physiol (Lond) 485:403–418

    CAS  Google Scholar 

  • Cheung NS, Carroll FY, Larm JA, Beart PM, Giardina SF (1998) Kainate-induced apoptosis correlates with c-Jun activation in cultured cerebellar granule cells. J Neurosci Res 52:69–82

    Article  PubMed  CAS  Google Scholar 

  • Dingledine R, Borges K, Bowie D, Traynelis SF (1999) The glutamate receptor ion channels. Pharmacol Rev 51:7–61

    PubMed  CAS  Google Scholar 

  • Fragioudaki K, Kouvelas ED, Cristiani R, Giompres P, Bagnoli P, Mitsacos A (2007) Expression of amino acid receptors and neural peptides in the weaver mouse brain. Brain Res 1140:132–152

    Article  PubMed  CAS  Google Scholar 

  • Giardina SF, Beart PM (2001) Excitotoxic profiles of novel, low affinity kainate receptor agonists in primary cultures of murine cerebellar granule cells. Neuropharmacol 41:421–432

    Article  CAS  Google Scholar 

  • Harkins AB, Dlouhy S, Ghetti B, Cahill AL, Won L, Heller B, Heller A, Fox AP (2000) Evidence of elevated intracellular calcium levels in weaver homozygote mice. J Physiol (Lond) 524:447–455

    Article  CAS  Google Scholar 

  • Kofuji P, Hofer M, Millen KJ, Millonig HJ, Davidson N, Lester HA, Hatten ME (1996) Functional analysis of the weaver mutant GIRK2K+ channel and rescue of weaver granule cells. Neuron 16:941–952

    Article  PubMed  CAS  Google Scholar 

  • Komuro H, Rakic P (1993) Modulation of neuronal migration by NMDA receptors. Science 260:95–97

    Article  PubMed  CAS  Google Scholar 

  • Liesi P, Wright JM (1996) Weaver granule neurons are rescued by calcium channels antagonists and antibodies against a neurite outgrowth domain of the B2 chain of laminin. J Cell Biol 134:477–486

    Article  PubMed  CAS  Google Scholar 

  • Liesi P, Wright JM, Krauthamer V (1997) BAPTA-AM and ethanol protect cerebellar granule neurons from the destructive effect of the weaver gene. J Neurosci Res 48:571–579

    Article  PubMed  CAS  Google Scholar 

  • Liu HN, Almazan G (1995) Glutamate induces c-fos proto-ongogene expression and inhibits proliferation in oligodendrocyte progenitors: receptor characterization. Eur J Neurosci 7:2355–2363

    Article  PubMed  CAS  Google Scholar 

  • LoTurco JJ, Owens DF, Heath MJ, Davis MB, Kriegstein AR (1995) GABA and glutamate depolarize cortical progenitor cells and inhibit DNA synthesis. Neuron 15:1287–1298

    Article  PubMed  CAS  Google Scholar 

  • Maric D, Liu QY, Grant GM, Andreasis JD, Hu Q, Chang YH, Barker JL, Joseph J, Stenger DA, Ma W (2000) Functional ionotropic glutamate receptors emerge during terminal cell division and early neuronal differentiation of rat neuroepithelial cells. J Neurosci Res 61:652–662

    Article  PubMed  CAS  Google Scholar 

  • Migheli A, Attanasio A, Lee WH, Bayer SA, Bernardino G (1995) Detection of apoptosis in weaver cerebellum by electron microscopic in situ end-labeling of fragmented DNA. Neurosci Lett 199:53–56

    Article  PubMed  CAS  Google Scholar 

  • Pemberton KE, Belcher SM, Ripellino JA, Howe JR (1998) High-affinity kainate-type ion channels in rat cerebellar granule cells. J Physiol (Lond) 510:401–420

    Article  CAS  Google Scholar 

  • Rakic P, Sidman R (1973) Weaver mutant mouse cerebellum: defective neuronal migration secondary to abnormality of Bergman glia. Proc Natl Acad Sci USA 70:240–250

    Article  PubMed  CAS  Google Scholar 

  • Ripellino JA, Neve RL, Howe JR (1998) Expression and heteromeric interactions of non-N-methyl-D-aspartate glutamate receptor subunits in the developing and adult cerebellum. Neuroscience 2:485–497

    Google Scholar 

  • Smith T, Yang L-Y, Howe JR (1999) Distinct kainate receptor phenotypes in immature and mature mouse cerebellar granule cells. J Physiol 517(1):51–58

    Article  PubMed  CAS  Google Scholar 

  • Surmeier DJ, Mermelstein PG, Goldowitz D (1996) The weaver mutation of GIRK2 results in a loss of inwardly rectifying K+ current in cerebellar granule cells. Proc Natl Acad Sci USA 93:11191–11195

    Article  PubMed  CAS  Google Scholar 

  • Verdaguer E, Garcia-Jorda E, Canudas AM, Dominguez E, Jimenez A, Pubill D, Escubedo E, Pallas JC, Camins A (2002) Kainic acid-induced apoptosis in cerebellar granule neurons: an attempt at cell cycle re-entry. Neuroreport 13:413–416

    Article  PubMed  CAS  Google Scholar 

  • Wüllner U, Standaert DC, Testa CM, Penney JB, Young AB (1997) Differential expression of kainate receptors in the basal ganglia of the developing and adult rat brain. Brain Res 768:215–223

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, Medical School, University of Patras, 26500, Patras, Greece

    Konstantinos Spiliopoulos, Kleopatra Fragioudaki, Elias Kouvelas & Ada Mitsacos

  2. Laboratory of Human and Animal Physiology, Department of Biology, University of Patras, 26500, Patras, Greece

    Panagiotis Giompres

Authors
  1. Konstantinos Spiliopoulos
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  2. Kleopatra Fragioudaki
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  3. Panagiotis Giompres
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  4. Elias Kouvelas
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  5. Ada Mitsacos
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Correspondence to Konstantinos Spiliopoulos.

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Spiliopoulos, K., Fragioudaki, K., Giompres, P. et al. Expression of GluR6 kainate receptor subunit in granular layer of weaver mouse cerebellum. J Neural Transm 116, 417–422 (2009). https://doi.org/10.1007/s00702-009-0199-8

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  • DOI: https://doi.org/10.1007/s00702-009-0199-8

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