Pochon N A, Menoud A, Tseng J L, Zurn A D, Aebischer P
Gene Therapy Center, Centre Hospitalier Universitaire Vaudois, Lausanne University Medical School, Switzerland.
Eur J Neurosci. 1997 Mar;9(3):463-71. doi: 10.1111/j.1460-9568.1997.tb01623.x.
Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor which has been purified on the basis of its ability to promote the survival of dopaminergic neurons in vitro. GDNF has subsequently been cloned and its sequence shown to be distantly related to transforming growth factor-beta (TGF-beta). To identify GDNF expressing cells in the adult rat brain, in situ hybridization using a digoxygenin (DIG)-labelled riboprobe has been performed. Our results show that GDNF mRNA is mainly expressed in neurons and that its synthesis is not restricted to dopaminergic areas. It is widely expressed in the cortex, the hippocampus, the striatum, the substantia nigra, the thalamus, the cerebellum and the spinal cord. Neuronal GDNF expression varies among brain regions as determined by the intensity of the in situ signal. Double labelling of the substantia nigra using tyrosine hydroxylase immunohistochemistry, associated with GDNF in situ hybridization, show that the majority of dopaminergic neurons express GDNF. The widespread expression of GDNF throughout the adult brain suggests that its administration in Parkinson's disease should be restricted to the altered structures, in order to avoid possible deleterious side effects.
胶质细胞系源性神经营养因子（GDNF）是一种强效神经营养因子，它是基于其在体外促进多巴胺能神经元存活的能力而被纯化出来的。随后，GDNF被克隆，其序列显示与转化生长因子-β（TGF-β）有较远的亲缘关系。为了鉴定成年大鼠脑中表达GDNF的细胞，已使用地高辛（DIG）标记的核糖探针进行原位杂交。我们的结果表明，GDNF mRNA主要在神经元中表达，其合成并不局限于多巴胺能区域。它在皮质、海马体、纹状体、黑质、丘脑、小脑和脊髓中广泛表达。根据原位信号的强度确定，神经元GDNF表达在不同脑区有所不同。使用酪氨酸羟化酶免疫组织化学与GDNF原位杂交对黑质进行双重标记，结果显示大多数多巴胺能神经元表达GDNF。GDNF在整个成年大脑中的广泛表达表明，在帕金森病中给予GDNF时应仅限于病变结构，以避免可能的有害副作用。
