Selectively increased sensitivity of cerebellar granule cells to AMPA receptor-mediated excitotoxicity in a mouse model of Batten disease
Copyright policy )Selectively increased sensitivity of cerebellar granule cells to AMPA receptor-mediated excitotoxicity in a mouse model of Batten disease
Batten disease, a lysosomal storage disorder, is caused by mutations in the CLN3 gene. The Cln3-knockout (Cln3-/-) mouse model of the disease exhibits many characteristic pathological features of the human disorder. Here, we show that Cln3-/- mice, similarly to Batten disease patients, have a deficit in cerebellar motor coordination. To explore the possible cellular cause of this functional impairment, we compared the vulnerability of wild type (WT) and Cln3-/- cerebellar granule cell cultures to different toxic insults. We have found that cultured Cln3-/- cerebellar granule cells are selectively more vulnerable to AMPA-type glutamate receptor-mediated toxicity than their WT counterparts. This selective sensitivity was also observed in organotypic cerebellar slice cultures. Our results suggest that lack of the CLN3 protein has a significant influence on the function of AMPA receptors in cerebellar granule neurons, and that AMPA receptor dysregulation may be a major contributor to the cerebellar dysfunction in Batten disease.
- University of Rochester United States
Cerebellar granule cells, Cell Survival, Neurosciences. Biological psychiatry. Neuropsychiatry, Mice, Organ Culture Techniques, Neuronal Ceroid-Lipofuscinoses, Cerebellum, AMPA, Animals, Receptors, AMPA, Cells, Cultured, Mice, Knockout, Neurons, Cerebellar slice cultures, Membrane Glycoproteins, Cell Death, Cortical cultures, Kainate, Disease Models, Animal, NMDA, Mutation, Psychomotor Performance, RC321-571, Molecular Chaperones
Cerebellar granule cells, Cell Survival, Neurosciences. Biological psychiatry. Neuropsychiatry, Mice, Organ Culture Techniques, Neuronal Ceroid-Lipofuscinoses, Cerebellum, AMPA, Animals, Receptors, AMPA, Cells, Cultured, Mice, Knockout, Neurons, Cerebellar slice cultures, Membrane Glycoproteins, Cell Death, Cortical cultures, Kainate, Disease Models, Animal, NMDA, Mutation, Psychomotor Performance, RC321-571, Molecular Chaperones
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