Long-term NR2B expression in the cerebellum alters granule cell development and leads to NR2A down-regulation and motor deficits

K. Schlett, Isabelle Pieri, Friedrich Metzger, Lara Marchetti, Frank Steigerwald, Ekrem Dere, Dániel Kirilly, Krisztián Tárnok, Brigitta Barabás, Ágnes Kis Varga, Jeannette Gerspach, Joseph P. Huston, Klaus Pfizenmaier, Georg Köhr, Ulrich L M Eisel

Research output: Contribution to journalArticle

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Abstract

N-methyl-d-aspartate receptor (NMDAR) composition in granule cells changes characteristically during cerebellar development. To analyze the importance of NR2B replacement by NR2C and NR2A subunits until the end of the first month of age, we generated mice with lasting NR2B expression but deficiency for NR2C (NR2C-2B mice). Mutant phenotype was different from NR2C knock-out mice as loss of granule cells and morphological changes in NR2C/2B cerebellar architecture were already evident from the second postnatal week. Increased NR2B subunit levels led also to a gradual down-regulation of cerebellar NR2A levels, preceding the development of motor impairment in adult animals. Therefore, cerebellar NR2A is important for proper motor coordination and cannot be replaced by long-term expression of NR2B. Consequently, the physiological exchange of NMDA receptor subunits during cerebellar granule cell maturation is important for accurate postnatal development and function.

Original languageEnglish
Pages (from-to)215-226
Number of pages12
JournalMolecular and Cellular Neuroscience
Volume27
Issue number3
DOIs
Publication statusPublished - Nov 2004

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Cerebellum
Down-Regulation
N-Methyl-D-Aspartate Receptors
Knockout Mice
Phenotype
aspartic acid receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience

Cite this

Long-term NR2B expression in the cerebellum alters granule cell development and leads to NR2A down-regulation and motor deficits. / Schlett, K.; Pieri, Isabelle; Metzger, Friedrich; Marchetti, Lara; Steigerwald, Frank; Dere, Ekrem; Kirilly, Dániel; Tárnok, Krisztián; Barabás, Brigitta; Kis Varga, Ágnes; Gerspach, Jeannette; Huston, Joseph P.; Pfizenmaier, Klaus; Köhr, Georg; Eisel, Ulrich L M.

In: Molecular and Cellular Neuroscience, Vol. 27, No. 3, 11.2004, p. 215-226.

Research output: Contribution to journalArticle

Schlett, K, Pieri, I, Metzger, F, Marchetti, L, Steigerwald, F, Dere, E, Kirilly, D, Tárnok, K, Barabás, B, Kis Varga, Á, Gerspach, J, Huston, JP, Pfizenmaier, K, Köhr, G & Eisel, ULM 2004, 'Long-term NR2B expression in the cerebellum alters granule cell development and leads to NR2A down-regulation and motor deficits', Molecular and Cellular Neuroscience, vol. 27, no. 3, pp. 215-226. https://doi.org/10.1016/j.mcn.2004.05.008
Schlett, K. ; Pieri, Isabelle ; Metzger, Friedrich ; Marchetti, Lara ; Steigerwald, Frank ; Dere, Ekrem ; Kirilly, Dániel ; Tárnok, Krisztián ; Barabás, Brigitta ; Kis Varga, Ágnes ; Gerspach, Jeannette ; Huston, Joseph P. ; Pfizenmaier, Klaus ; Köhr, Georg ; Eisel, Ulrich L M. / Long-term NR2B expression in the cerebellum alters granule cell development and leads to NR2A down-regulation and motor deficits. In: Molecular and Cellular Neuroscience. 2004 ; Vol. 27, No. 3. pp. 215-226.
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