Granholm A C, Srivastava N, Mott J L, Henry S, Henry M, Westphal H, Pichel J G, Shen L, Hoffer B J
Department of Basic Science, University of Colorado Health Sciences Center, Denver 80262, USA.
J Neurosci. 1997 Feb 1;17(3):1168-78. doi: 10.1523/JNEUROSCI.17-03-01168.1997.
Glial cell line-derived neurotrophic factor (GDNF) is a member of the TGF-beta superfamily of growth factors with neurotrophic activity on midbrain dopaminergic neurons and on developing and mature motoneurons of the brainstem and spinal cord. To investigate the extent of GDNF dependency of central and peripheral nervous structures during development, we have performed an immunohistochemical analysis of sections from the whole head including brain, peripheral ganglia, developing teeth and tongue, as well as intestines, in mutant mice lacking a part of the third exon that encodes the GDNF protein. As described previously, these null-mutated mice lack most of the enteric nerve plexus and are subject to agenesis or severe dysgenesis of the kidneys. In the present communication, we examined the development of vibrissae and incisor and molar teeth, as well as the innervation of these structures, and found no differences between null-mutated and control mice. A decrease in the immunohistochemical labeling intensity with tyrosine hydroxylase was observed in the superior cervical ganglion (SCG), as well as in the pontine nucleus locus coeruleus, and the sympathetic innervation of blood vessels and glands in the head was significantly decreased. None of the brain nuclei studied exhibited any significant decreases in the total number of neurons, but the packing density of neurons in the nucleus locus coeruleus was decreased. These data indicate that GDNF might be one neurotrophic factor that contributes to the development of central and peripheral noradrenergic neurons.
胶质细胞系源性神经营养因子（GDNF）是转化生长因子-β超家族生长因子的一员，对中脑多巴胺能神经元以及脑干和脊髓中发育中和成熟的运动神经元具有神经营养活性。为了研究发育过程中中枢和外周神经结构对GDNF的依赖程度，我们对缺失编码GDNF蛋白的第三外显子部分的突变小鼠的整个头部切片进行了免疫组织化学分析，这些切片包括脑、外周神经节、发育中的牙齿和舌头以及肠道。如先前所述，这些无效突变小鼠缺乏大部分肠神经丛，并且会出现肾脏发育不全或严重发育异常。在本报告中，我们检查了触须、门齿和臼齿的发育以及这些结构的神经支配情况，发现无效突变小鼠和对照小鼠之间没有差异。在上颈神经节（SCG）以及脑桥核蓝斑中，观察到酪氨酸羟化酶免疫组织化学标记强度降低，并且头部血管和腺体的交感神经支配显著减少。所研究的脑核中，没有一个神经元总数出现任何显著减少，但蓝斑核中神经元的堆积密度降低。这些数据表明，GDNF可能是一种有助于中枢和外周去甲肾上腺素能神经元发育的神经营养因子。
