Differential effects of endogenous brain-derived neurotrophic factor on the survival of axotomized sensory neurons in dorsal root ganglia: A possible role for the p75 neurotrophin receptor

• Published in: Neuroscience Vol. 132; no. 3; pp. 591 - 603
• Main Authors: Zhou, X.-F., Li, W.-P., Zhou, F.H.-H., Zhong, J.-H., Mi, J.-X., Wu, L.L.-Y., Xian, C.J.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 2005; Elsevier
• Subjects: Animals; Animals, Newborn; Antibodies - pharmacology; Apoptosis - drug effects; Apoptosis - physiology; Axotomy - methods; BDNF apoptosis; Biological and medical sciences; Blotting, Western - methods; Brain-Derived Neurotrophic Factor - immunology; Brain-Derived Neurotrophic Factor - physiology; Cell Count - methods; Cell Survival - drug effects; Cell Survival - physiology; DRG culture; Enzyme-Linked Immunosorbent Assay - methods; Functional Laterality; Fundamental and applied biological sciences. Psychology; Ganglia, Spinal - cytology; Ganglia, Spinal - growth & development; Immunohistochemistry - methods; In Situ Nick-End Labeling - methods; Indoles; Mice; Mice, Knockout; Neurons, Afferent - drug effects; Neurons, Afferent - physiology; Organ Culture Techniques; p75 neurotrophin receptor; Rats; Receptor, Nerve Growth Factor; Receptor, trkB - metabolism; Receptors, Nerve Growth Factor - deficiency; Receptors, Nerve Growth Factor - physiology; sciatic nerve injury; Time Factors; Vertebrates: nervous system and sense organs; PBS; BDNF apoptosis; p75 neurotrophin receptor; BDNF; sciatic nerve injury; NGF; NT3; P; NSIgG; PBST; rh; DRG; DRG culture; Neurotrophin; Spinal cord; p75 receptor; Central nervous system; Survival; Cell death; Sensory neuron; Spinal ganglion; Brain derived neurotrophic factor; Lesion; Sciatic nerve; Apoptosis
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2004.12.034

After peripheral nerve injury, axotomized sensory neurons in dorsal root ganglia (DRG) undergo apoptosis and up-regulate brain-derived neurotrophic factor (BDNF). We tested whether endogenous BDNF plays any role in the survival of axotomized sensory neurons using in vitro and in vivo models. In the in vitro model, treatment with BDNF antibody significantly reduced apoptosis of sensory neurons in DRG explants from both adult and neonate rats and adult mice cultured for 48 h. Consistently, exogenous BDNF increased the percentage of apoptotic neurons in the DRGs from mice. The effects of the BDNF antibody and BDNF were not seen in DRGs from p75NTR −/− mice. In the in vivo model, sciatic nerve transection in neonatal rats decreased the total number of neurons in the injured DRG and treatment with antiserum to BDNF significantly exaggerated the loss of DRG neurons. Numbers of sensory neurons expressing BDNF and p75NTR in cultured DRGs increased but that expressing TrkB decreased. In contrast, sciatic nerve transection in vivo reduced the numbers of neurons expressing both p75NTR and TrkB but increased the numbers of cells expressing BDNF, 1 and 7 days after the surgery. These results suggest that BDNF may have differential effects on the survival of sensory neurons depending on the expression of p75NTR. While endogenous BDNF induced apoptosis of axotomized sensory neurons through p75NTR in vitro where more neurons expressed p75NTR, it prevented apoptosis in vivo where fewer neurons expressed p75NTR after sciatic nerve transection.