Nerve growth factor alters p75 neurotrophin receptor-induced effects in mouse facial motoneurons following axotomy.
The p75 neurotrophin receptor (p75(NTR)) has been implicated as being detrimental for cell survival in facial motoneurons following injury. Although facial motoneurons do not respond to nerve growth factor (NGF) under normal circumstances, this study shows that NGF can interfere with p75(NTR)-mediated cell survival effects on motoneurons following injury. Twenty-five days following injury, the proportion of surviving axotomized neurons in NGF/p75(+/+) mice, which overexpress NGF, was significantly higher compared to wild-type mice, while NGF/p75(-/-) mice, which overexpress NGF but carry two mutated alleles for p75(NTR), had fewer neurons compared to wild-type and p75(-/-) mice, which carry two mutated alleles for p75(NTR), resulting in a lack of functional expression of this receptor. Sympathetic axons sprouted into the axotomized facial nucleus of both NGF/p75(+/+) and NGF/p75(-/-) following injury, due to transgene expression of NGF in reactive astrocytes. Removal of these sympathetic axons enhanced the number of surviving axotomized neurons in NGF/p75(-/-) mice but not in NGF/p75(+/+) mice. Although motoneurons do not express trkA and should therefore be unresponsive to NGF, our results reveal that NGF can influence p75-mediated motoneuron survival following axotomy.
Ferri
Catharine C
CC
Department of Physiology, Queen's University, ON K7L 3N6, Kingston, Canada.
Ghasemlou
Nader
N
Bisby
Mark A
MA
Kawaja
Michael D
MD
D000818:Animals; D019771:Axotomy / Q000706:statistics & numerical data; D002470:Cell Survival / Q000502:physiology; D005154:Facial Nerve / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis* / Q000172:deficiency* / Q000235:genetics
D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D020932:Nerve Growth Factor