RRC ID 49600
Author Zhang H, Song L, Chang Y, Wu M, Kuang X, Jiang H, Wu S.
Title Potential deficit from decreased cerebellar granule cell migration in serine racemase-deficient mice is reversed by increased expression of GluN2B and elevated levels of NMDAR agonists.
Journal Mol Cell Neurosci
Abstract Inward migration of cerebellar granule cells (CGCs) after birth is critical for lamination in the cerebellar cortex. N-methyl-d-aspartate (NMDA) subtype of glutamate receptor (NMDAR) tethering CGCs into Bergmann glial fibers mediates the inward movement during the glial-dependent migratory phase. Activation of NMDAR depends on simultaneous binding of the GluN2 subunit by glutamate, and of the GluN1 subunit by d-serine or glycine; d-serine is believed to be an endogenous ligand of NMDAR. We hypothesized that lamination of the cerebellar cortex may be compromised in Srr (the gene for serine racemase (SR)) mutated mice (Srrnull) because of significantly low levels of d-serine per se. Indeed, the external germinal cell layer (EGL) in Srrnull was thicker than in sibling wild-type (WT) mice on postnatal day7 (P7), which accords with decreased CGC migration in Srrnull mice. However, the cerebellar laminar structure in Srrnull mice was normal on P12 and later. Feeding d-serine to pregnant mice abrogated the increased EGL thickness in Srrnull mice on P7. To determine the underlying mechanism of abnormal laminar structure during cerebellar development in Srrnull mice, we examined NMDAR subunits and their ligands. We found increased GluN2B on P10 and increased glycine during P7-12 in the cerebellar homogenates from Srrnull mice compared with the corresponding values from sibling WT mice. In summary, the study revealed how the potential defect in early cerebellar development caused by Srr mutation is circumvented by a compensatory mechanism. This knowledge advances understanding of the adaptation of cerebellar development under the condition of Srr mutation.
Volume 85
Pages 119-126
Published 2017-12-1
DOI 10.1016/j.mcn.2017.09.005
PII S1044-7431(17)30206-3
PMID 28939329
MeSH Animals Cell Movement / physiology Cerebellum / growth & development* Cerebellum / metabolism* Mice Mice, Mutant Strains Mutation Neurogenesis / physiology* Racemases and Epimerases / deficiency* Racemases and Epimerases / genetics Receptors, N-Methyl-D-Aspartate / agonists Receptors, N-Methyl-D-Aspartate / biosynthesis*
IF 3.182
Times Cited 3
Mice RBRCGD000099