Effect of nerve injury on the number of dorsal root ganglion neurons and autotomy behavior in adult Bax-deficient mice

Abstract

Background

The proapoptotic molecule BAX, plays an important role in mitochondrial apoptotic pathway. Dorsal root ganglion (DRG) neurons depend on neurotrophic factors for survival at early developmental stages. Withdrawal of neurotrophic factors will induce apoptosis in DRG neurons, but this type of cell death can be delayed or prevented in neonatal Bax knockout (KO) mice. In adult animals, evidence also shows that DRG neurons are less dependent upon neurotrophic factors for survival. However, little is known about the effect of Bax deletion on the survival of normal and denervated DRG neurons in adult mice.

Methods

A unilateral sciatic nerve transection was performed in adult Bax KO mice and wild-type (WT) littermates. Stereological method was employed to quantify the number of lumbar-5 DRG neurons 1 month post-surgery. Nerve injury-induced autotomy behavior was also examined on days 1, 3, and 7 post-surgery.

Results

There were significantly more neurons in contralateral DRGs of KO mice as compared with WT mice. The number of neurons was reduced in ipsilateral DRGs in both KO and WT mice. No changes in size distributions of DRG neuron profiles were detected before or after nerve injury. Injury-induced autotomy behavior developed much earlier and was more serious in KO mice.

Conclusion

Although postnatal death or loss of DRG neurons is partially prevented by Bax deletion, this effect cannot interfere with long-term nerve injury-induced neuronal loss. The exaggerated self-amputation behavior observed in the mutant mice indicates that Bax deficiency may enhance the development of spontaneous pain following nerve injury.

Keywords:

• apoptosis
• axotomy
• cell death
• chronic pain
• unbiased counting method
• sensory neurons

Acknowledgments

This work was supported by the Research Council of Norway, the KG Jebsen Foundation, and the China Scholarship Council (CSC) award to Dr. Chuang Lyu (Harbin Institute of Technology, 2013). We especially would like to thank Dr. Tomas Hökfelt for his generous sharing of the mutant mice and his laboratory facilities.

Author contributions

CL and GWL performed experiments. CL, AM and TJSS analyzed the data and wrote the manuscript. All authors contributed toward data analysis, drafting and critically revising the paper and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.