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NGF-Dependent and BDNF-Dependent DRG Sensory Neurons Deploy Distinct Degenerative Signaling Mechanisms
Andrés de León1,2, Julien Gibon2, Philip A Barker3
1Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada.
Eneuro
|December 29, 2020
Summary
Brain-derived neurotrophic factor (BDNF) withdrawal triggers sensory neuron degeneration via BAX and reactive oxygen species (ROS), unlike nerve growth factor (NGF) deprivation. This reveals distinct signaling pathways in developmental neuron death.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are crucial trophic factors for sensory neuron survival during nervous system development.
- While NGF deprivation-induced neuronal death pathways are understood, mechanisms of BDNF deprivation-induced degeneration remain largely unknown.
Purpose of the Study:
- To investigate the molecular signaling pathways involved in sensory neuron degeneration following BDNF withdrawal.
- To compare these mechanisms with those triggered by NGF deprivation.
Main Methods:
- Utilized an in vitro dorsal root ganglion (DRG) culture model.
- Examined the effects of inhibiting Trk receptors, PKC, protein translation (CHX), and caspases (zVAD-fmk).
- Assessed the roles of BAX and reactive oxygen species (ROS) in BDNF withdrawal-induced degeneration.
Main Results:
- Inhibition of Trk receptors, PKC, protein translation, or caspases protected against NGF deprivation but not BDNF withdrawal.
- BDNF withdrawal-induced degeneration of sensory neurons requires BAX.
- Degeneration triggered by BDNF withdrawal appears to rely on ROS generation, not caspases.
Conclusions:
- Signaling pathways regulating developmental sensory neuron death exhibit both similarities and differences between NGF and BDNF deprivation.
- BDNF deprivation-induced neuronal degeneration involves distinct molecular mechanisms, including BAX and ROS, compared to NGF deprivation.
