1. Increased [3H]D-aspartate release and changes in glutamate receptor expression in the hippocampus of the mnd mouse
- Author
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Paolo Bigini, Giambattista Bonanno, Sara Barbera, Marco Milanese, Tiziana Bonifacino, Fabrizio Gardoni, Annalisa Longhi, Monica Di Luca, Tiziana Mennini, and Elena Fumagalli
- Subjects
medicine.medical_specialty ,Excitotoxicity ,Glutamate receptor ,Hippocampus ,AMPA receptor ,Hippocampal formation ,Biology ,medicine.disease_cause ,medicine.disease ,Cellular and Molecular Neuroscience ,Glutamatergic ,Epilepsy ,Endocrinology ,nervous system ,CLN8 ,Internal medicine ,medicine ,Neuroscience - 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, Ca²⁺-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.
- Published
- 2012