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Updated: Jun 3, 2026

Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons
Published on: November 6, 2017
Role for apoptosis-inducing factor in the physiological death of cerebellar neurons
1Neuroscience Division, Institute of Cell Physiology, National Autonomous University of Mexico, Mexico City, Mexico.
Abstract:
Apoptosis-inducing factor (AIF) is implicated in caspase-independent apoptotic-like death. AIF released from mitochondria translocates to the nucleus, where it mediates some apoptotic events such as chromatin condensation and DNA degradation. Here, the role of AIF in the neuronal death was studied under physiological conditions. When we analyzed the cellular localization of AIF during cerebellar development, we found a significant increase in the number of neurons with nuclear AIF localization in an age-dependent manner. On the other hand, cerebellar granule neurons (CGN) chronically cultured in low concentration of potassium (5 mM; K5) die with apoptotic-like characteristics after five days. In the present study we found that K5 induces a caspase-dependent apoptotic-like death of CGN as well as a late nuclear translocation of AIF. When CGN death induced by K5 was carried out in the presence of a general inhibitor of caspases, there was a slight decrement of cell death, but neurons eventually died by showing apoptotic-like features such as phosphatidylserine translocation and nuclear condensation. Besides, there was a significant increment of nuclear AIF translocation. These findings support the idea that AIF could be involved in apoptotic-like death of CGN and that it could be an alternative mechanism of neuronal death during cerebellar development.
Insights
Apoptosis-inducing factor (AIF) plays a role in neuronal death during cerebellar development. AIF contributes to caspase-dependent and independent cell death pathways in cerebellar granule neurons.
Area of Science:
- Neuroscience
- Cell Biology
Background:
- Apoptosis-inducing factor (AIF) is involved in caspase-independent cell death.
- AIF translocates from mitochondria to the nucleus, inducing chromatin condensation and DNA degradation.
Purpose of the Study:
- To investigate the role of AIF in neuronal death under physiological conditions.
- To examine AIF's involvement in cerebellar granule neuron (CGN) death induced by low potassium (K5).
Main Methods:
- Analysis of AIF cellular localization during cerebellar development.
- Culture of CGN in low potassium (5 mM) and treatment with caspase inhibitors.
- Assessment of cell death markers like phosphatidylserine translocation and nuclear condensation.
Main Results:
- Nuclear AIF localization increased with age during cerebellar development.
- K5 induced caspase-dependent CGN death with late nuclear AIF translocation.
- Caspase inhibition only slightly reduced K5-induced CGN death, with increased nuclear AIF.
Conclusions:
- AIF is implicated in K5-induced apoptotic-like death of CGN.
- AIF may represent an alternative neuronal death mechanism during cerebellar development.
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