The biological responses of axotomized adult motoneurons to brain-derived neurotrophic factor.
Recent studies showed that brain-derived neurotrophic factor (BDNF) prevents developing motoneurons from naturally occurring and axotomy-induced cell death. Here we examined whether adult motoneurons retain responsiveness to BDNF. Consistent with previous studies, we found that adult spinal and brainstem motoneurons expressed the mRNA of BDNF receptor, trkB. In addition, the trkB immunoreactivities were readily detected in the adult spinal and brainstem motoneurons. We then demonstrated that axotomized adult motoneurons responded to exogenous BDNF. BDNF administered locally markedly attenuated the lesion-induced decrease of ChAT immunoreactivity and activity and enhanced the lesion-induced reexpression of low-affinity NGF receptor immunoreactivity in adult facial motoneurons. Furthermore, we found BDNF administered subcutaneously, intravenously, and into the cerebral ventricle attenuated the lesion-induced decrease of ChAT immunoreactivity in adult facial motoneurons in a dose-dependent fashion. Our data indicate that adult motoneurons retain their responsiveness to BDNF, suggesting that BDNF may be useful as a therapeutic agent for adult motoneuron disease.
Yan
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Department of Neurobiology, Amgen, Inc., Amgen Center, Thousand Oaks, CA 91320.
Matheson
C
C
Lopez
O T
OT
Miller
J A
JA
D000818:Animals; D001369:Axons / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor; D003714:Denervation; D004305:Dose-Response Relationship, Drug; D005154:Facial Nerve / Q000166:cytology / Q000187:drug effects; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor