Moore M W, Klein R D, Fariñas I, Sauer H, Armanini M, Phillips H, Reichardt L F, Ryan A M, Carver-Moore K, Rosenthal A
Department of Molecular Biology, Genentech, Inc., South San Francisco, California 94080, USA.
Nature. 1996 Jul 4;382(6586):76-9. doi: 10.1038/382076a0.
Glial cell-line derived neurotrophic factor (GDNF) is a potent survival factor for embryonic midbrain dopaminergic, spinal motor, cranial sensory, sympathetic, and hindbrain noradrenergic neurons, and is available to these cells in vivo. It is therefore considered a physiological trophic factor and a potential therapeutic agent for Parkinson's disease, amyotrophic lateral sclerosis, and Alzheimer's disease. Here we show that at postnatal day 0 (P0), GDNF-deficient mice have deficits in dorsal root ganglion, sympathetic and nodose neurons, but not in hindbrain noradrenergic or midbrain dopaminergic neurons. These mice completely lack the enteric nervous system (ENS), ureters and kidneys. Thus GDNF is important for the development and/or survival of enteric, sympathetic and sensory neurons and the renal system, but is not essential for catecholaminergic neurons in the central nervous system (CNS).
胶质细胞系源性神经营养因子(GDNF)是胚胎中脑多巴胺能神经元、脊髓运动神经元、颅感觉神经元、交感神经元和后脑去甲肾上腺素能神经元强有力的存活因子,且在体内这些细胞均可获得该因子。因此,它被视为一种生理性营养因子以及帕金森病、肌萎缩侧索硬化症和阿尔茨海默病的潜在治疗药物。在此我们表明,在出生后第0天(P0),GDNF基因缺陷小鼠的背根神经节、交感神经元和结状神经元存在缺陷,但后脑去甲肾上腺素能神经元或中脑多巴胺能神经元无缺陷。这些小鼠完全缺乏肠神经系统(ENS)、输尿管和肾脏。因此,GDNF对肠、交感和感觉神经元以及肾脏系统的发育和/或存活很重要,但对中枢神经系统(CNS)中的儿茶酚胺能神经元并非必不可少。