Hudson J, Granholm A C, Gerhardt G A, Henry M A, Hoffman A, Biddle P, Leela N S, Mackerlova L, Lile J D, Collins F
University of Colorado Health Sciences Center, Denver 80262, USA.
Brain Res Bull. 1995;36(5):425-32. doi: 10.1016/0361-9230(94)00224-o.
Recently, a novel glial cell line-derived neurotrophic factor (GDNF) has been identified, cloned, and shown to have potent survival- and growth-promoting activity on fetal rat midbrain dopaminergic neurons in cell culture. In this study, we document marked and long-lasting effects on adult rat midbrain dopaminergic neurons in vivo after intracranial administration. A single injection of this factor into the substantia nigra elicited a dose-dependent increase in both spontaneous and amphetamine-induced motor activity, and a decrease in food consumption, lasting 7-10 days. Using immunocytochemistry, we found sprouting of tyrosine hydroxylase-positive neurites towards the injection site, and increased tyrosine hydroxylase immunoreactivity of the ipsilateral striatum was produced by GDNF. There was also a marked and dose-dependent increase in dopamine turnover in the substantia nigra and striatum, and in ipsilateral dopamine levels in the substantia nigra. Little or no effects of GDNF were seen on norepinephrine or serotonin levels. The neurochemical changes on dopaminergic afferents persist for at least 3 weeks after a single intracranial injection of 10 micrograms. Taken together, these data suggest that this glial cell line-derived factor has a potent influence on adult rat dopamine neurons and may have a potentially important role as a trophic factor for these neurons.
最近，一种新型的胶质细胞源性神经营养因子（GDNF）已被鉴定、克隆，并显示在细胞培养中对胎鼠中脑多巴胺能神经元具有强大的存活和促生长活性。在本研究中，我们记录了颅内给药后对成年大鼠中脑多巴胺能神经元的显著且持久的影响。向黑质单次注射该因子会引起自发运动和苯丙胺诱导的运动活性呈剂量依赖性增加，以及食物摄入量减少，持续7 - 10天。使用免疫细胞化学方法，我们发现酪氨酸羟化酶阳性神经突向注射部位生长，并且GDNF使同侧纹状体的酪氨酸羟化酶免疫反应性增加。黑质和纹状体中的多巴胺周转率以及黑质中同侧多巴胺水平也有显著且剂量依赖性的增加。GDNF对去甲肾上腺素或血清素水平几乎没有影响。单次颅内注射10微克后，多巴胺能传入神经的神经化学变化至少持续3周。综上所述，这些数据表明这种胶质细胞源性因子对成年大鼠多巴胺神经元有强大影响，并且可能作为这些神经元的一种营养因子发挥潜在的重要作用。
