| Autor: |
Attila D. Kovács, Jill M. Weimer, David A. Pearce |
| Jazyk: |
angličtina |
| Rok vydání: |
2006 |
| Předmět: |
|
| Zdroj: |
Neurobiology of Disease, Vol 22, Iss 3, Pp 575-585 (2006) |
| Druh dokumentu: |
article |
| ISSN: |
1095-953X |
| DOI: |
10.1016/j.nbd.2005.12.018 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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