The role of neurotrophins in the maintenance of the spinal cord motor neurons and the dorsal root ganglia proprioceptive sensory neurons.
The aim of this study was to approach the question of neuronal dependence on neurotrophins during embryonic development in mice in a way other than gene targeting. We employed amyogenic mouse embryos and fetuses that develop without any skeletal myoblasts or skeletal muscle and consequently lose motor and proprioceptive neurons. We hypothesized that if, in spite of the complete inability to maintain motor and proprioceptive neurons, the remaining spinal and dorsal root ganglia tissues of amyogenic fetuses still contain any of the neurotrophins, that particular neurotrophin alone is not sufficient for the maintenance of motor and proprioceptive neurons. Moreover, if the remaining spinal and dorsal root ganglia tissues still contain any of the neurotrophins, that particular neurotrophin alone may be sufficient for the maintenance of the remaining neurons (i.e., mostly non-muscle- and a few muscle-innervating neurons). To test the role of the spinal cord and dorsal root ganglia tissues in the maintenance of its neurons, we performed immunohistochemistry employing double-mutant and control tissues and antibodies against neurotrophins and their receptors. Our data suggested that: (a) during the peak of motor neuron cell death, the spinal cord and dorsal root ganglia distribution of neurotrophins was not altered; (b) the distribution of BDNF, NT-4/5, TrkB and TrkC, and not NT-3, was necessary for the maintenance of the spinal cord motor neurons; (c) the distribution of BDNF, NT-4/5 and TrkC, and not NT-3 and Trk B, was necessary for the maintenance of the DRG proprioceptive neurons; (d) NT-3 was responsible for the maintenance of the remaining neurons and glia in the spinal cord and dorsal root ganglia (possibly via TrkB).
Stephens
Heather E
HE
Dalhousie University, Department of Anatomy and Neurobiology, 5850 College Street, Halifax, NS, Canada B3H 5X1.
Belliveau
Anne C
AC
Gupta
Jagdish S
JS
Mirkovic
Slobodan
S
Kablar
Boris
B
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D016923:Cell Death; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology* / Q000196:embryology / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000502:physiology*; D017570:MyoD Protein / Q000235:genetics / Q000502:physiology; D051787:Myogenic Regulatory Factor 5 / Q000235:genetics / Q000502:physiology; D009414:Nerve Growth Factors / Q000235:genetics / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D011247:Pregnancy; D011434:Proprioception / Q000502:physiology*; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D020812:Receptor, trkC / Q000235:genetics / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; C497418:Myf5 protein, mouse; D017570:MyoD Protein; D051787:Myogenic Regulatory Factor 5; D009414:Nerve Growth Factors; D017475:Receptors, Nerve Growth Factor; C089191:neurotrophin 4(5) receptor; D020813:Receptor, trkB; D020812:Receptor, trkC