title: Long-term NR2B expression in the cerebellum alters granule cell development and leads to NR2A down-regulation and motor deficits.
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.
authors.affiliation: Institute of Cell Biology and Immunology, University of Stuttgart, D-70569 Stuttgart, Germany.
authors.forename: Katalin
authors.initials: K
authors.lastname: Schlett
authors.forename: Isabelle
authors.initials: I
authors.lastname: Pieri
authors.forename: Friedrich
authors.initials: F
authors.lastname: Metzger
authors.forename: Lara
authors.initials: L
authors.lastname: Marchetti
authors.forename: Frank
authors.initials: F
authors.lastname: Steigerwald
authors.forename: Ekrem
authors.initials: E
authors.lastname: Dere
authors.forename: Dániel
authors.initials: D
authors.lastname: Kirilly
authors.forename: Krisztián
authors.initials: K
authors.lastname: Tárnok
authors.forename: Brigitta
authors.initials: B
authors.lastname: Barabás
authors.forename: Agnes Kis
authors.initials: AK
authors.lastname: Varga
authors.forename: Jeannette
authors.initials: J
authors.lastname: Gerspach
authors.forename: Josephp
authors.initials: J
authors.lastname: Huston
authors.forename: Klaus
authors.initials: K
authors.lastname: Pfizenmaier
authors.forename: Georg
authors.initials: G
authors.lastname: Köhr
authors.forename: Ulrich L M
authors.initials: UL
authors.lastname: Eisel
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019957:Motor Skills Disorders / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis* / Q000235:genetics; D013995:Time
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate