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Updated: Jun 28, 2026

Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons
Published on: November 6, 2017
Differential insult-dependent recruitment of the intrinsic mitochondrial pathway during neuronal programmed cell
S Diwakarla1, P Nagley, M L R Hughes
1Brian Injury and Repair Program, Florey Neuroscience Institutes, The University of Melbourne, Parkville, Victoria 3010, Australia.
Abstract:
Programmed cell death contributes to neurological diseases and may involve mitochondrial dysfunction with redistribution of apoptogenic proteins. We examined neuronal death to elucidate whether the intrinsic mitochondrial pathway and the crosstalk between caspase-dependent/-independent injury was differentially recruited by stressors implicated in neurodegeneration. After exposure of cultured cerebellar granule cells to various insults, the progression of injury was correlated with mitochondrial involvement, including the redistribution of intermembrane space (IMS) proteins, and patterns of protease activation. Injury occurred across a continuum from Bax- and caspase-dependent (trophic- factor withdrawal) to Bax-independent, calpain-dependent (excitotoxicity) injury. Trophic-factor withdrawal produced classical recruitment of the intrinsic pathway with activation of caspase-3 and redistribution of cytochrome c, whereas excitotoxicity induced early redistribution of AIF and HtrA2/Omi, elevation of intracellular calcium and mitochondrial depolarization. Patterns of engagement of neuronal programmed cell death and the redistribution of mitochondrial IMS proteins were canonical, reflecting differential insult-dependencies.
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