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Updated: Aug 29, 2026
Facial Nerve Axotomy in Mice: A Model to Study Motoneuron Response to Injury
Published on: February 23, 2015
Response of motoneurons to neonatal sciatic nerve axotomy in Bax-knockout mice
Woong Sun1, Ronald W Oppenheim
1Department of Neurobiology and Anatomy and Neuroscience Program, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Abstract:
Neonatal motoneurons (MNs) die rapidly after axotomy, a response that is mediated by the pro-apoptotic gene Bax and is followed by a mitochondria-mediated apoptotic cascade. Although motoneurons in neonatal Bax-deficient mice fail to degenerate following axotomy, it has not been previously examined whether the rescued MNs can regenerate following injury. We report here that although spinal MNs in Bax-knockout (Bax-KO) mice survive indefinitely, they undergo severe atrophy by 14 days after axotomy. By 1 month following axotomy, MN regeneration was observed and cellular atrophy was partially reversed. Interestingly, we observed that all MNs, including those previously rescued from normal developmental cell death in the embryo by Bax deletion, exhibit a regenerative response to peripheral nerve injury. The regenerative response may be mediated by specific trophic factors because the expression of glial cell line-derived neurotrophic factor (GDNF) was greatly increased in the proximal stump of injured nerves and application of a GDNF-blocking antibody greatly reduced regeneration/regrowth of rescued MNs in Bax-KO mice. These results indicate that MNs rescued from developmental or injury-induced cell death by Bax deletion have the potential to regenerate or regrow in response to nerve-derived signals following neonatal axotomy.
Insights
Neonatal motoneurons (MNs) rescued from death by Bax deletion survive but atrophy after injury. These neurons can regenerate, with glial cell-derived neurotrophic factor (GDNF) playing a key role in their recovery.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Death Pathways
Background:
- Neonatal motoneurons (MNs) undergo rapid apoptosis after axotomy, mediated by the pro-apoptotic gene Bax.
- While Bax-deficient mice show MN survival post-axotomy, their regenerative capacity remains unexamined.
Purpose of the Study:
- To investigate the regenerative potential of neonatal MNs rescued from cell death by Bax deletion following peripheral nerve injury.
- To elucidate the molecular mechanisms, particularly the role of trophic factors like GDNF, in MN regeneration.
Main Methods:
- Utilized Bax-knockout (Bax-KO) mice to rescue neonatal MNs from developmental and injury-induced cell death.
- Performed axotomy on neonatal spinal MNs and assessed survival, atrophy, and regeneration over time.
- Investigated the role of glial cell-derived neurotrophic factor (GDNF) by examining its expression and using blocking antibodies.
Main Results:
- Spinal MNs in Bax-KO mice survived indefinitely but showed severe atrophy by 14 days post-axotomy.
- Regeneration and partial reversal of atrophy were observed by 1 month after axotomy.
- Glial cell-derived neurotrophic factor (GDNF) expression increased in injured nerves, and GDNF blockade reduced MN regeneration.
Conclusions:
- Neonatal MNs rescued from cell death by Bax deletion possess the capacity for regeneration following peripheral nerve injury.
- The regenerative response is influenced by nerve-derived signals, with GDNF being a critical mediator.
- These findings highlight the potential for neuronal recovery even in cells rescued from initial cell death pathways.
