| First Author | Selimi F | Year | 2000 |
| Journal | J Neurosci | Volume | 20 |
| Issue | 3 | Pages | 992-1000 |
| PubMed ID | 10648704 | Mgi Jnum | J:59973 |
| Mgi Id | MGI:1352355 | Doi | 10.1523/JNEUROSCI.20-03-00992.2000 |
| Citation | Selimi F, et al. (2000) Target-related and intrinsic neuronal death in Lurcher mutant mice are both mediated by caspase-3 activation. J Neurosci 20(3):992-1000 |
| abstractText | The Lurcher (Lc) mutation in the delta2 glutamate receptor gene leads to the presence of a constitutive inward current in the cerebellar Purkinje cells of Lurcher heterozygous mice and to the postnatal degeneration of these neurons. In addition, cerebellar granule cells and olivary neurons of Lc/+ mice die as an indirect effect of the mutation after the loss of their target Purkinje cells. The apoptotic nature of Lc/+ Purkinje cell death remains controversial. To address this question, we studied the involvement of caspase-3, a key effector of apoptosis, in the neurodegenerative processes occurring in Lc/+ cerebellum. Several antibodies recognizing different regions of caspase-3 were used in immunoblotting and immunohistochemical experiments. We demonstrate that pro-caspase-3 is specifically upregulated in the dying Lc/+ Purkinje cells, but not in granule cells and olivary neurons, suggesting that different death-inducing signals trigger variant apoptotic pathways in the CNS. The subcellular localization of pro-caspase-3 was shown to be cytoplasmic and mitochondrial. Active caspase-3 as well as DNA fragmentation was found in numerous granule cells and some Purkinje cells of the Lc/+ cerebellum. Thus, caspase-3 activation is involved in both the direct and indirect neuronal death induced by the Lurcher mutation, strongly supporting the idea that the Lc/+ Purkinje cell dies by apoptosis. |
