The effects of sciatic nerve axotomy on spinal motoneurons in neonatal Bax-deficient mice.
During development, the survival of spinal motoneurons depends on the integrity of the connection to their peripheral targets. Peripheral nerve axotomy induces apoptosis in neonatal neurons supplying axons to the nerve. Bax is known to promote apoptosis among developing neurons. To examine the effect of axotomy on spinal motoneurons in Bax-deficient (Bax-/-) and wild-type neonatal mice (Bax+/+), the sciatic nerve was axotomized on postnatal day (P) 0, and motoneurons in the fourth lumbar (L4) segment were visualized at P7 by acetylcholinesterase (AChE) histochemical staining. Presumably due to the reduction in naturally occurring cell death resulting from the deficiency of Bax, there were about 50% more AChE-positive cells in Bax-/- than in Bax+/+. Motoneurons in the dorsolateral motor pool of L4 project through the sciatic nerve. In Bax+/+, axotomy of the sciatic nerve induced significant cell loss in the pool. Most motoneurons survived such axotomy in Bax-/-, although they appeared atrophic and their AChE expression was decreased. Motoneurons may receive vital support retrogradely from their targets, and loss of such support may lead to hypofunction of spinal motoneurons, as indicated by the reduced production of AChE by axotomized motoneurons and their small size in Bax-/-.
Kinugasa
Tomonori
T
Department of Physiology, Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba City, Ibaraki 305-8575, Japan. tkinu@mike.md.tsukuba.ac.jp
Ozaki
Shigeru
S
Hamanaka
Souji
S
Kudo
Norio
N
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics*; D019771:Axotomy; D002232:Carbocyanines; D002454:Cell Differentiation / Q000235:genetics*; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D012183:Retrograde Degeneration / Q000235:genetics / Q000378:metabolism; D012584:Sciatic Nerve / Q000293:injuries / Q000601:surgery; D013116:Spinal Cord / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D051028:bcl-2-Associated X Protein
C035005:3,3'-dihexadecylindocarbocyanine; C494827:Bax protein, mouse; D002232:Carbocyanines; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D000110:Acetylcholinesterase