Author: J. Takács 1
View More View Less
  • 1 Péter Pázmány Catholic University — Semmelweis University Infibionic and Neurobiological Plasticity Research Group of the Hungarian Academy of Sciences Budapest Hungary
Restricted access

Postnatal development of the cerebellum lasts for weeks in rodents and can be disturbed by systemic 5-bromo-2′-deoxyuridine (BrdU) administration. This thymidine analogue incorporates into the DNA of proliferating cells, and results in more or less serious damage or death of granule cells, the most actively dividing neuronal population in the developing cerebellar cortex. Further consequences of postnatal BrdU administration are the interrupted postnatal migration and integration as well as partial loss of cerebellar Purkinje cells. In the present study, C57Bl6 mice were administered with 50 μg/g body weight BrdU, one sc. injection daily, between P0 and P11 postnatal days, respectively. Large “cavities” appeared in the cytoplasm of a subpopulation of Purkinje cells by P7 in about one-third of administered animals, their number were high at P9 and P11, especially in vermal lobules VIII, IX, and X. By P13 and P15 the number and size of the cavities (and PCs exhibiting unusual morphology) decreased. EM studies revealed that the unusual Purkinje cells received numerous axonal inputs of unknown origin, first of all on their somatic and dendritic spines. The transitory appearance of a subpopulation of Purkinje cells possessing unusual morphology refers to the influence of other (neuronal, glial, or both) cells on their regular differentiation.

  • Altman, J. Anderson, W. J. (1972) Experimental reorganization of the cerebellar cortex. 1. Morphological effects of elimination of all microneurons with prolonged X-irradiation started at birth. J. Comp. Neurol. 146, 355–406.

    Anderson W. J. , 'Experimental reorganization of the cerebellar cortex. 1. Morphological effects of elimination of all microneurons with prolonged X-irradiation started at birth ' (1972 ) 146 J. Comp. Neurol. : 355 -406.

    • Search Google Scholar
  • Altman, J., Bayer, S. A. (1997) Development of the cerebellar system in relation to its evolution, structure and functions. CRC Press, Boca Raton.

    Bayer S. A. , '', in Development of the cerebellar system in relation to its evolution, structure and functions , (1997 ) -.

  • Bannigan, J., Langman, J. (1979) The cellular effect of 5-bromodeoxyuridine on the mammalian embryo. J. Embryol. Exp. Morphol. 50, 123–135.

    Langman J. , 'The cellular effect of 5-bromodeoxyuridine on the mammalian embryo ' (1979 ) 50 J. Embryol. Exp. Morphol. : 123 -135.

    • Search Google Scholar
  • Bonthius, D. J., Bonthius, N. E., Napper, R. M., Astley, S. J., Clarren, S. K., West, J. R. (1996) Purkinje cell deficits in nonhuman primates following weekly exposure to ethanol during gestation. Teratology 53, 230–236.

    West J. R. , 'Purkinje cell deficits in nonhuman primates following weekly exposure to ethanol during gestation ' (1996 ) 53 Teratology : 230 -236.

    • Search Google Scholar
  • Caddy, K. W. T., Biscoe, T. J. (1979) Structural and quantitative studies on the normal C3H and Lurcher mutant mouse. Philos. Trans. R. Soc. Lond. B 287, 167–201.

    Biscoe T. J. , 'Structural and quantitative studies on the normal C3H and Lurcher mutant mouse ' (1979 ) 287 Philos. Trans. R. Soc. Lond. B : 167 -201.

    • Search Google Scholar
  • De Barry, J., Gombos, G., Klupp, T., Hamori, J. (1987) Alterations of mouse cerebellar circuits following methylazoxymethanol treatment during development: Immunocytochemical and electron microscopic study. J. Comp. Neurol. 61, 253–265.

    Hamori J. , 'Alterations of mouse cerebellar circuits following methylazoxymethanol treatment during development: Immunocytochemical and electron microscopic study ' (1987 ) 61 J. Comp. Neurol. : 253 -265.

    • Search Google Scholar
  • De Camilli, P., Miller, P. E., Levitt, P., Walter, U., Greengard, P. (1984) Anatomy of cerebellar Purkinje cells in the rat determined by a specific immunohistochemical marker. Neuroscience 11, 761–817.

    Greengard P. , 'Anatomy of cerebellar Purkinje cells in the rat determined by a specific immunohistochemical marker ' (1984 ) 11 Neuroscience : 761 -817.

    • Search Google Scholar
  • del Rio, J. A., Soriano, E. (1989) Immunocytochemical detection of 5-bromodeoxyuridine incorporation in the central nervous system of the mouse. Brain Res. 49, 311–317.

    Soriano E. , 'Immunocytochemical detection of 5-bromodeoxyuridine incorporation in the central nervous system of the mouse ' (1989 ) 49 Brain Res. : 311 -317.

    • Search Google Scholar
  • Dikraniana, K., Qina, Y.-O., Labruyerea, J., Nemmersa, B., Olneya, J. W. (2005) Ethanol-induced neuroapoptosis in the developing rodent cerebellum and related brain stem structures. Dev. Brain Res. 155, 1–13.

    Olneya J. W. , 'Ethanol-induced neuroapoptosis in the developing rodent cerebellum and related brain stem structures ' (2005 ) 155 Dev. Brain Res. : 1 -13.

    • Search Google Scholar
  • Dolbeare, F. (1995) Bromodeoxyuridine: a diagnostic tool in biology and medicine. Part I. Historical perspectives, histochemical methods and cell kinetics. Histochem. J. 27, 339–369.

    Dolbeare F. , 'Bromodeoxyuridine: a diagnostic tool in biology and medicine. Part I. Historical perspectives, histochemical methods and cell kinetics ' (1995 ) 27 Histochem. J. : 339 -369.

    • Search Google Scholar
  • Dolbeare, F. (1996) Bromodeoxyuridine: a diagnostic tool in biology and medicine. Part III. Proliferation in normal, injured and diseased tissue, growth factors, differentiation, DNA replication sites and in situ hybridization. Histochem. J. 28, 531–575.

    Dolbeare F. , 'Bromodeoxyuridine: a diagnostic tool in biology and medicine. Part III. Proliferation in normal, injured and diseased tissue, growth factors, differentiation, DNA replication sites and in situ hybridization ' (1996 ) 28 Histochem. J. : 531 -575.

    • Search Google Scholar
  • Fonnum, F., Lock, E. A. (2000) Cerebellum as a target for toxic substances. Toxicology Letters 112–113, 9–16.

    Lock E. A. , 'Cerebellum as a target for toxic substances ' (2000 ) 112–113 Toxicology Letters : 9 -16.

    • Search Google Scholar
  • Garcia, R. I., Werner, I., Szabo, G. (1979) Effect of 5-bromo-2′-deoxyuridine on growth and differentiation of cultured embryonic retinal pigment cells. In Vitro 15, 779–788.

    Szabo G. , 'Effect of 5-bromo-2′-deoxyuridine on growth and differentiation of cultured embryonic retinal pigment cells ' (1979 ) 15 In Vitro : 779 -788.

    • Search Google Scholar
  • Görcs, T. J., Penke, B., Boti, Z., Katarova, Z., Hámori, J. (1993) Immunohistochemical visualization of a metabotropic glutamate receptor. NeuroReport 4, 283–286.

    Hámori J. , 'Immunohistochemical visualization of a metabotropic glutamate receptor ' (1993 ) 4 NeuroReport : 283 -286.

    • Search Google Scholar
  • Grandes, P., Mateos, J. M., Ruegg, D., Kuhn, R., Knöpfel, T. (1994) Different cellular localization of three splice variants of the mGluR1 metabotropic glutamate receptor in rat cerebellum. NeuroReport 5, 2249–2252.

    Knöpfel T. , 'Different cellular localization of three splice variants of the mGluR1 metabotropic glutamate receptor in rat cerebellum ' (1994 ) 5 NeuroReport : 2249 -2252.

    • Search Google Scholar
  • Gratzner, H. G. (1982) Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: a new reagent for detection of DNA replication. Science 218, 474–475.

    Gratzner H. G. , 'Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: a new reagent for detection of DNA replication ' (1982 ) 218 Science : 474 -475.

    • Search Google Scholar
  • Grimaldi, P., Rossi, F. (2006) Lack of neurogenesis in the adult rat cerebellum after Purkinje cell degeneration and growth factor infusion. Eur. J. Neurosci. 23, 2657–2668.

    Rossi F. , 'Lack of neurogenesis in the adult rat cerebellum after Purkinje cell degeneration and growth factor infusion ' (2006 ) 23 Eur. J. Neurosci. : 2657 -2668.

    • Search Google Scholar
  • Hámori, J., Takács, J., Görcs, T. J. (1996) Immunocytochemical localization of mGluR1a metabotropic glutamate receptor in inhibitory neurons of the cerebellar cortex. Acta Biol. Hung. 47, 181–194.

    Görcs T. J. , 'Immunocytochemical localization of mGluR1a metabotropic glutamate receptor in inhibitory neurons of the cerebellar cortex ' (1996 ) 47 Acta Biol. Hung. : 181 -194.

    • Search Google Scholar
  • Kiss, J., Görcs, T. J., Kuhn, R., Knöpfel, T., Csáky, Á., Halász, B. (1996) Distribution of metabotropic glutamate receptor 1a in the rat hypothalamus: an immunocytochemical study using monoclonal and polyclonal antibody. Acta Biol. Hung. 47, 221–237.

    Halász B. , 'Distribution of metabotropic glutamate receptor 1a in the rat hypothalamus: an immunocytochemical study using monoclonal and polyclonal antibody ' (1996 ) 47 Acta Biol. Hung. : 221 -237.

    • Search Google Scholar
  • Hatten, M. E., Heintz, N. (1995) Mechanisms of neural patterning and specification in the developing cerebellum. Annu. Rev. Neurosci. 18, 385–408

    Heintz N. , 'Mechanisms of neural patterning and specification in the developing cerebellum ' (1995 ) 18 Annu. Rev. Neurosci. : 385 -408.

    • Search Google Scholar
  • Heckroth, J. A., Goldowitz, D., Eisenman, L. M. (1989) Purkinje cell reduction in the reeler mutant mouse: a quantitative immunohistochemical study. J. Comp. Neurol. 279, 546–555.

    Eisenman L. M. , 'Purkinje cell reduction in the reeler mutant mouse: a quantitative immunohistochemical study ' (1989 ) 279 J. Comp. Neurol. : 546 -555.

    • Search Google Scholar
  • Herrup, K., Trenkner, E. (1987) Regional differences in cytoarchitecture of the weaver cerebellum suggest a new model for weaver gene action. Neuroscience 23, 871–885.

    Trenkner E. , 'Regional differences in cytoarchitecture of the weaver cerebellum suggest a new model for weaver gene action ' (1987 ) 23 Neuroscience : 871 -885.

    • Search Google Scholar
  • Hillman, D. E., Chen, S. (1981) Vulnerability of cerebellar development in malnutrition-I. Quantitation of layer volume and neuron numbers. Neuroscience 6, 1249–1262.

    Chen S. , 'Vulnerability of cerebellar development in malnutrition-I. Quantitation of layer volume and neuron numbers ' (1981 ) 6 Neuroscience : 1249 -1262.

    • Search Google Scholar
  • Hirano, A., Dembitzer, H. M., Jones, J. (1972) An electron microscopic study of cycasin-induced cerebellar alterations. J. Neuropathol. Exp. Neurol. 31, 113–125.

    Jones J. , 'An electron microscopic study of cycasin-induced cerebellar alterations ' (1972 ) 31 J. Neuropathol. Exp. Neurol. : 113 -125.

    • Search Google Scholar
  • Jande, S. S., Maler, L., Lawson, D. E. M. (1981) Immunohistochemical mapping of vitamin-ddependent calcium-binding protein in brain. Nature 294, 765–767.

    Lawson D. E. M. , 'Immunohistochemical mapping of vitamin-ddependent calcium-binding protein in brain ' (1981 ) 294 Nature : 765 -767.

    • Search Google Scholar
  • Kolb, B., Pedersen, B., Ballermann, M., Gibb, R., Whishaw, I. Q. (1999) Embryonic and postnatal injections of bromodeoxyuridine produce age-dependent morphological and behavioral abnormalities. J. Neurosci. 19, 2337–2346.

    Whishaw I. Q. , 'Embryonic and postnatal injections of bromodeoxyuridine produce age-dependent morphological and behavioral abnormalities ' (1999 ) 19 J. Neurosci. : 2337 -2346.

    • Search Google Scholar
  • Kwok, K. H., Law, K. B., Wong, R. N., Yung, K. K. (1999) Immunolesioning of nerve growth factor p75 receptor-containing neurons in the rat brain by a novel immunotoxin: anti-p75-anti-mouse IgGtrichosanthin conjugates. Brain. Res. 846, 154–163.

    Yung K. K. , 'Immunolesioning of nerve growth factor p75 receptor-containing neurons in the rat brain by a novel immunotoxin: anti-p75-anti-mouse IgGtrichosanthin conjugates ' (1999 ) 846 Brain. Res. : 154 -163.

    • Search Google Scholar
  • Light, K. E., Blecher, S. M., Peirce, D. R. (2002) Time course and manner of Purkinje neuron death following a single ethanol exposure on postnatal day 4 in the developing rat. Neuroscience 114, 327.

    Peirce D. R. , 'Time course and manner of Purkinje neuron death following a single ethanol exposure on postnatal day 4 in the developing rat ' (2002 ) 114 Neuroscience : 327 -.

    • Search Google Scholar
  • Martin, L. J., Blackstone, C. D., Huganir, R. L., Price, D. L. (1992) Cellular localization of a metabotropic glutamate receptor in rat brain. Neuron 9, 259–270.

    Price D. L. , 'Cellular localization of a metabotropic glutamate receptor in rat brain ' (1992 ) 9 Neuron : 259 -270.

    • Search Google Scholar
  • Miale, I. L., Sidman, R. L. (1961) An autoradiographic analysis of histogenesis in the mouse cerebellum. Exp. Neurol. 4, 277–296.

    Sidman R. L. , 'An autoradiographic analysis of histogenesis in the mouse cerebellum ' (1961 ) 4 Exp. Neurol. : 277 -296.

    • Search Google Scholar
  • Moller-Madsen, B., Danscher, G. (1986) Localization of mercury in CNS of the rat. I. Mercuric chloride (HgCl2) per os. Environ. Res. 41, 29–43.

    Danscher G. , 'Localization of mercury in CNS of the rat. I. Mercuric chloride (HgCl2) per os ' (1986 ) 41 Environ. Res. : 29 -43.

    • Search Google Scholar
  • Nagao, T., Kuwagata, M., Saito, Y. (1998) Effects of prenatal exposure to 5-bromo-2′-deoxyuridine on the developing brain and reproductive function in male mouse offspring. Reprod. Toxicol. 12, 477–487.

    Saito Y. , 'Effects of prenatal exposure to 5-bromo-2′-deoxyuridine on the developing brain and reproductive function in male mouse offspring ' (1998 ) 12 Reprod. Toxicol. : 477 -487.

    • Search Google Scholar
  • Ozol, K., Hayden, J. M., Oberdick, J., Hawkes, R. (1999) Transverse zones in the vermis of the mouse cerebellum. J. Comp. Neurol. 412, 95–111.

    Hawkes R. , 'Transverse zones in the vermis of the mouse cerebellum ' (1999 ) 412 J. Comp. Neurol. : 95 -111.

    • Search Google Scholar
  • Ozol, K., Hawkes, R. (1997) Calbindin organization in the newborn mouse cerebellum: genealogical analysis of Purkinje cell compartments. Soc. Neurosci. Abstr. 23, 19.

    Hawkes R. , 'Calbindin organization in the newborn mouse cerebellum: genealogical analysis of Purkinje cell compartments ' (1997 ) 23 Soc. Neurosci. Abstr. : 19 -.

    • Search Google Scholar
  • Sekerkova, G., Ilijic, E., Mugnaini, E. (2004) Bromodeoxyuridine administered during neurogenesis of the projection neurons causes cerebellar defects in rat. J. Comp. Neurol. 470, 221–239.

    Mugnaini E. , 'Bromodeoxyuridine administered during neurogenesis of the projection neurons causes cerebellar defects in rat ' (2004 ) 470 J. Comp. Neurol. : 221 -239.

    • Search Google Scholar
  • Sotelo, C., Rio, J. P. (1988) Cerebellar malformation obtained in rats by early postnatal treatment with 6-aminonicotinamide. Role of neuron-glia interactions in cerebellar development. Neuroscience 5, 1737–1759.

    Rio J. P. , 'Cerebellar malformation obtained in rats by early postnatal treatment with 6-aminonicotinamide. Role of neuron-glia interactions in cerebellar development ' (1988 ) 5 Neuroscience : 1737 -1759.

    • Search Google Scholar
  • Takács, J., Gombos, G., Görcs, T., Becker, T., de Barry, J., Hámori, J. (1977) Distribution of metabotropic glutamate receptor type 1a in the Purkinje cell dendritic spines is independent of the presence of presynaptic parallel fibers. J. Neurosci. Res. 50, 433–442.

    Hámori J. , 'Distribution of metabotropic glutamate receptor type 1a in the Purkinje cell dendritic spines is independent of the presence of presynaptic parallel fibers ' (1977 ) 50 J. Neurosci. Res. : 433 -442.

    • Search Google Scholar
  • Takács, J., Hámori, J., Görcs, T. J. (1994) MGluR1a immunoreactivity in Purkinje cells of the developing rat cerebellar cortex. Eur. J. Neurosci. Suppl. 7, 51.

    Görcs T. J. , 'MGluR1a immunoreactivity in Purkinje cells of the developing rat cerebellar cortex ' (1994 ) 7 Eur. J. Neurosci. Suppl. : 51 -.

    • Search Google Scholar
  • Takacs, J., Borostyankoi, Z. A., Veisenberger, E., Vastagh, C., Vig, J., Gorcs, T. J., Hamori, J. (2000) Postnatal development of unipolar brush cells in the cerebellar cortex of cat. J. Neurosci. Res. 61, 107–115.

    Hamori J. , 'Postnatal development of unipolar brush cells in the cerebellar cortex of cat ' (2000 ) 61 J. Neurosci. Res. : 107 -115.

    • Search Google Scholar
  • Takacs, J., Vig, J., Vastagh, Cs., Hamori, J. (2003) Effect of 5-bromo-2′-deoxyuridine (BrdU) on the postnatal development of cerebellum. In: Sixth IBRO World Congress of Neuroscience, July 10–15, Prague, Abstracts, p. 144.

  • Takacs, J., Vig, J., Hamori, J. (2006) Unusual morphology of Purkinje cells following postnatal BrdU administration in the cerebellar cortex of developing mouse. Clinical Neuroscience. Supplement 1, pp. 64.

    Hamori J. , 'Unusual morphology of Purkinje cells following postnatal BrdU administration in the cerebellar cortex of developing mouse ' (2006 ) 1 Clinical Neuroscience. Supplement : 64 -.

    • Search Google Scholar
  • Takács, J., Víg, J., Hámori, J. (2006) Vascular damage following postnatal BrdU administration in the cerebellar cortex of mouse. FENS 5th Forum, Vienna, July 8–12, 2006. Abstract book, pp. 229.

  • Taupin, P. (2007) BrdU immunohistochemistry for studying adult neurogenesis: paradigms, pitfalls, limitations, and validation. Brain Res. Rev. 53, 198–214.

    Taupin P. , 'BrdU immunohistochemistry for studying adult neurogenesis: paradigms, pitfalls, limitations, and validation ' (2007 ) 53 Brain Res. Rev. : 198 -214.

    • Search Google Scholar
  • Víg, J., Takács, J., Vastagh, C., Baldauf, Z., Veisenberger, E., Hámori, J. (2003) Distribution of mGluR1a and SMI 311 immunoreactive Lugaro cells in the kitten cerebellum. J. Neurocytol. 32, 217–227.

    Hámori J. , 'Distribution of mGluR1a and SMI 311 immunoreactive Lugaro cells in the kitten cerebellum ' (2003 ) 32 J. Neurocytol. : 217 -227.

    • Search Google Scholar
  • Wassef, M., Zanetta, J. P., Brehier, A., Sotelo, C. (1985) Transient biochemical compartmentalization of Purkinje-cells during early cerebellar development. Dev. Biol. 111, 129–137.

    Sotelo C. , 'Transient biochemical compartmentalization of Purkinje-cells during early cerebellar development ' (1985 ) 111 Dev. Biol. : 129 -137.

    • Search Google Scholar
  • Wassef, M., Angaut, P., Arsenio-Nunes, L., Bourrat, F., Sotelo, C. (1992) Purkinje cell heterogenity: its role in organizing the topography of the cerebellar cortex connections. In: Llinas, R., Sotelo, C. (eds) The cerebellum revisited. Springer-Verlag, New York-Heidelberg-Berlin, pp. 5–21.

    Sotelo C. , '', in The cerebellum revisited , (1992 ) -.

  • Wright, D. D., Blackstone, C. D., Huganir, R. L., Ryugo, D. K. (1996) Immunocytochemical localization of the mGluR1a metabotropic glutamate receptor in the dorsal cochlear nucleus. J. Comp. Neurol. 364, 729–745.

    Ryugo D. K. , 'Immunocytochemical localization of the mGluR1a metabotropic glutamate receptor in the dorsal cochlear nucleus ' (1996 ) 364 J. Comp. Neurol. : 729 -745.

    • Search Google Scholar
  • Yu, W. H. A. (1975) The effect of 5-bromodeoxyurudine on the postnatal development of the rat cerebellum. Anat. Rec. 181, 516–517.

    Yu W. H. A. , 'The effect of 5-bromodeoxyurudine on the postnatal development of the rat cerebellum ' (1975 ) 181 Anat. Rec. : 516 -517.

    • Search Google Scholar

Editorial Board

    1. Csányi, Vilmos (Göd)
    1. Dudits, Dénes (Szeged)
    1. Falus, András (Budapest)
    1. Fischer, Ernő (Pécs)
    1. Gábriel, Róbert (Pécs)
    1. Gulya, Károly (Szeged)
    1. Gulyás, Balázs (Stockholm)
    1. Hajós, Ferenc (Budapest)
    1. Hámori, József (Budapest)
    1. Heszky, László (Gödöllő)
    1. Hideg, Éva (Szeged)
    1. E. Ito (Sanuki)
    1. Janda, Tibor (Martonvásár)
    1. Kavanaugh, Michael P. (Missoula)
    1. Kása, Péter (Szeged)
    1. Klein, Éva (Stockholm)
    1. Kovács, János (Budapest)
    1. Brigitte Mauch-Mani (Neuchâtel)
    1. Nässel, Dick R. (Stockholm)
    1. Nemcsók, János (Szeged)
    1. Péczely, Péter (Gödöllő)
    1. Roberts, D. F. (Newcastle-upon-Tyne)
    1. Sakharov, Dimitri A. (Moscow)
    1. Singh, Meharvan (Fort Worth)
    1. Sipiczky, Mátyás (Debrecen)
    1. Szeberényi, József (Pécs)
    1. Székely, György (Debrecen)
    1. Tari, Irma (Szeged)
    1. Vágvölgyi, Csaba (Szeged),
    1. L. Zaborszky (Newark)

 

Acta Biologica Hungarica
P.O. Box 35
H-8237 Tihany, Hungary
Phone: (36 87) 448 244 ext. 103
Fax: (36 87) 448 006
E-mail: elekes@tres.blki.hu

Indexing and Abstracting Services:

  • Biological Abstracts
  • BIOSIS Previews
  • CAB Abstracts
  • Chemical Abstracts
  • Current Contents: Agriculture
  • Biology and Environmental Sciences
  • Elsevier BIOBASE
  • Global Health
  • Index Medicus
  • Index Veterinarius
  • Medline
  • Referativnyi Zhurnal
  • Science Citation Index
  • Science Citation Index Expanded (SciSearch)
  • SCOPUS
  • The ISI Alerting Services
  • Zoological Abstracts

 

Acta Biologica Hungarica
Language English
Size  
Year of
Foundation
1950
Publication
Programme
changed title
Volumes
per Year
 
Issues
per Year
 
Founder Magyar Tudományos Akadémia
Founder's
Address
H-1051 Budapest, Hungary, Széchenyi István tér 9.
Publisher Akadémiai Kiadó
Publisher's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Responsible
Publisher
Chief Executive Officer, Akadémiai Kiadó
ISSN 0236-5383 (Print)
ISSN 1588-256X (Online)