Neuronal death induced by stroke or trauma occurs via both necrosis and apoptosis. Cell death is not confined to the original traumatized cells, but is observed to spread to neighboring cells. This Drosophila model of neuronal necrosis makes use of a constitutively open cation channel (a mutant form of the mouse Mmus\Gria1 ionotropic glutamate receptor) expressed in neural cells.
Initial experiments used expression in a defined sets of cells in the developing eye. The resulting calcium overload triggers necrosis in the defined neurons, as well as extensive spreading of cell death, resulting in a dramatic reduction in the size of the adult eye. Genetic inhibition of apoptosis does not affect the eye defect; additional deaths appear to be largely confined to neurons, with less impact on glial cells. The system has been used for a genetic screen for suppressors of neuronal necrosis, and to genetically define pathways that impact neuronal necrosis, including the spreading phenomenon.
Experiments using a general neuronal driver combined with temperature-sensitive expression of the open cation channel (to limit duration) have been conducted to assess whether transcription and processing of small RNAs contribute to neuronal necrosis.
[updated Sep. 2021 by FlyBase; FBrf0222196]
Even a brief ischemic stroke may trigger complex cellular events that lead to both apoptotic and necrotic neuronal cell death in a progressive manner (Yuan, 2009; pubmed:19137430).
The mouse lurcher mutation (Mmus\Gria1Lc.UAS as introduced in Drosophila) results in catastrophic loss of cerebellar Purkinje cells in heterozygous animals; it has been associated with a large constitutive inward current which ultimately activates a programmed form of neuronal death (De Jager and Heintz, 1998; pubmed:9804384).
