Hory-Lee F, Russell M, Lindsay R M, Frank E
Department of Neurobiology, Anatomy, and Cell Science, University of Pittsburgh School of Medicine, PA 15213.
Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2613-7. doi: 10.1073/pnas.90.7.2613.
Target-dependent cell death of different sub-populations of sensory neurons may be regulated by different trophic factors. To investigate this possibility, we have taken advantage of the fact that the fractions of muscle sensory and cutaneous sensory neurons in chicken dorsal root ganglia (DRG) are probably different at different segmental levels, and we have compared the responses of chicken DRG from levels that do and do not innervate limb tissue to various growth factors in vitro. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) both supported neurite outgrowth from DRG explanted from all segmental levels. In contrast, neurotrophin 3 (NT-3) supported robust neurite growth only from DRG explanted from the cervical or lumbar levels, which innervate limb muscles. Similarly, NGF and BDNF both promoted survival of dissociated neurons from limb and nonlimb segmental levels, whereas NT-3 promoted survival of more neurons from limb compared to nonlimb levels. This suggests that muscle sensory neurons, which are probably more prevalent at the cervical and lumbar levels, may be specifically affected by NT-3. To evaluate this possibility directly, we compared the survival of retrogradely labeled muscle and cutaneous neurons in NGF, BDNF, and NT-3. Identified muscle sensory neurons survived best in vitro in the presence of NT-3, while the survival of identified cutaneous sensory neurons was greatest in NGF. This work provides direct evidence for a potential role of NT-3 versus NGF in the survival of a specific subpopulation of DRG neurons.
不同亚群感觉神经元的靶依赖性细胞死亡可能受不同营养因子的调节。为了探究这种可能性,我们利用了这样一个事实:鸡背根神经节(DRG)中肌肉感觉神经元和皮肤感觉神经元的比例在不同节段水平可能不同,并且我们比较了来自支配和不支配肢体组织的节段水平的鸡DRG对各种生长因子的体外反应。神经生长因子(NGF)和脑源性神经营养因子(BDNF)都支持从所有节段水平取出的DRG的神经突生长。相比之下,神经营养素3(NT-3)仅支持从支配肢体肌肉的颈段或腰段取出的DRG的强劲神经突生长。同样,NGF和BDNF都促进来自肢体和非肢体节段水平的解离神经元的存活,而与非肢体水平相比,NT-3促进来自肢体的更多神经元的存活。这表明可能在颈段和腰段更普遍的肌肉感觉神经元可能受到NT-3的特异性影响。为了直接评估这种可能性,我们比较了在NGF、BDNF和NT-3中逆行标记的肌肉和皮肤神经元的存活情况。已鉴定的肌肉感觉神经元在NT-3存在的情况下在体外存活最佳,而已鉴定的皮肤感觉神经元在NGF中存活最佳。这项工作为NT-3与NGF在DRG神经元特定亚群存活中的潜在作用提供了直接证据。