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.
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.
Zhou
X-F
XF
Department of Human Physiology, Flinders University of South Australia, GPO Box 2100, Adelaide 5001, Australia. xin-fu.zhou@flinders.edu.au
Li
W-P
WP
Zhou
F H-H
FH
Zhong
J-H
JH
Mi
J-X
JX
Wu
L L-Y
LL
Xian
C J
CJ
D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D019771:Axotomy / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000276:immunology / Q000502:physiology*; D002452:Cell Count / Q000379:methods; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D007839:Functional Laterality; D005727:Ganglia, Spinal / Q000166:cytology* / Q000254:growth & development; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D007211:Indoles; D051379:Mice; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D051381:Rats; D020800:Receptor, Nerve Growth Factor; D020813:Receptor, trkB / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000172:deficiency / Q000502:physiology*; D013997:Time Factors
D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D007211:Indoles; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; C007293:DAPI; D020813:Receptor, trkB