Increased [ 3H]D-aspartate release and changes in glutamate receptor expression in the hippocampus of the mnd mouse

Paolo Bigini, Marco Milanese, Fabrizio Gardoni, Annalisa Longhi, Tiziana Bonifacino, Sara Barbera, Elena Fumagalli, Monica Di Luca, Tiziana Mennini, Giambattista Bonanno

Research output: Contribution to journalArticlepeer-review

Abstract

Neuronal ceroid lipofuscinoses (NCLs) are a group of hereditary childhood diseases characterized mainly by lipopigment accumulation and a multisystemic pattern of symptoms including mental retardation, seizures, motor impairment, and blindness. The mnd mouse, carrying a mutation in the Cln8 gene, has been proposed as a model of epilepsy with mental retardation (EPMR, ornorthern epilepsy). We recently showed neuronal hyperexcitability and seizure hypersusceptibility in mnd mice. To elucidate the cellular mechanisms related to hippocampal hyperexcitability, the glutamatergic transmission and the expression of postsynaptic glutamate receptors were investigated in hippocampus. A significant increase in either spontaneous or KCl-stimulated overflow of [ 3H]D-aspartate was found in mnd mice compared with controls. This increase was maintained after DL-threo-β-benzyloxyaspartic acid (TBOA) treatment, suggesting a nonrelevant role for transporter-mediated release and supporting the involvement of exocytotic [ 3H]D-aspartate release. Accordingly, Ca 2+-dependent overflow induced by ionomycin was also increased in mnd mice. Levels of glutamate 1-3 AMPA receptor subunits were increased, and levels of the NR2A NMDA receptor subunit were decreased in the hippocampus of mnd mice, suggesting an adaptive response to glutamate overstimulation.

Original languageEnglish
Pages (from-to)1148-1158
Number of pages11
JournalJournal of Neuroscience Research
Volume90
Issue number6
DOIs
Publication statusPublished - Jun 2012

Keywords

  • Epilepsy
  • Excitotoxicity
  • Glutamate release
  • Mnd mice
  • Neuronal ceroid lipofuscinoses
  • Neuronal hyperexcitability

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Increased [ 3H]D-aspartate release and changes in glutamate receptor expression in the hippocampus of the mnd mouse'. Together they form a unique fingerprint.

Cite this