Yan Q, Matheson C, Lopez O T, Miller J A
Department of Neurobiology, Amgen, Inc., Amgen Center, Thousand Oaks, CA 91320.
J Neurosci. 1994 Sep;14(9):5281-91. doi: 10.1523/JNEUROSCI.14-09-05281.1994.
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.
最近的研究表明，脑源性神经营养因子（BDNF）可防止发育中的运动神经元因自然发生的和轴突切断诱导的细胞死亡。在此，我们研究了成年运动神经元是否保留对BDNF的反应性。与先前的研究一致，我们发现成年脊髓和脑干运动神经元表达BDNF受体trkB的mRNA。此外，在成年脊髓和脑干运动神经元中很容易检测到trkB免疫反应性。然后我们证明，轴突切断的成年运动神经元对外源性BDNF有反应。局部给予BDNF可显著减轻成年面神经运动神经元中损伤诱导的胆碱乙酰转移酶（ChAT）免疫反应性和活性的降低，并增强损伤诱导的低亲和力神经生长因子（NGF）受体免疫反应性的重新表达。此外，我们发现皮下、静脉内和脑室内给予BDNF可剂量依赖性地减轻成年面神经运动神经元中损伤诱导的ChAT免疫反应性的降低。我们的数据表明，成年运动神经元保留了对BDNF的反应性，这表明BDNF可能作为成年运动神经元疾病的治疗剂。
