Mount H T, Dean D O, Alberch J, Dreyfus C F, Black I B
Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway 08854, USA.
Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9092-6. doi: 10.1073/pnas.92.20.9092.
Glial cell line-derived neurotrophic factor (GDNF) promotes survival of midbrain dopaminergic neurons and motoneurons. Expression of GDNF mRNA in cerebellum raises the possibility that cells within this structure might also respond to GDNF. To examine potential trophic activities of GDNF, dissociated cultures of gestational day 18 rat cerebellum were grown for < or = 21 days in the presence of factor. GDNF increased Purkinje cell number without affecting the overall number of neurons or glial cells. A maximal response (50% above control) was elicited with GDNF at 1 pg/ml. Effects of GDNF on Purkinje cell differentiation were examined by scoring the morphologic maturation of cells in treated and control cultures. GDNF increased the proportion of Purkinje cells that displayed relatively mature morphologies, characterized by dendritic thickening and the development of spines and filopodial extensions. Morphologic maturation of the overall neuronal population was unaffected. In sum, our data indicate that GDNF is a potent survival and differentiation factor for Purkinje cells, the efferent neurons of cerebellar cortex. Together with its other actions, these findings raise the possibility that GDNF might be a critical trophic factor at multiple loci in neuronal circuits that control motor function.
胶质细胞系源性神经营养因子（GDNF）可促进中脑多巴胺能神经元和运动神经元的存活。小脑内GDNF mRNA的表达增加了该结构中的细胞可能也对GDNF产生反应的可能性。为了检测GDNF的潜在营养活性，将妊娠第18天大鼠小脑的解离培养物在该因子存在的情况下培养≤21天。GDNF增加了浦肯野细胞的数量，而不影响神经元或胶质细胞的总数。1 pg/ml的GDNF可引发最大反应（比对照高50%）。通过对处理组和对照组培养物中细胞的形态成熟度进行评分，研究了GDNF对浦肯野细胞分化的影响。GDNF增加了呈现相对成熟形态的浦肯野细胞的比例，其特征为树突增粗以及棘突和丝状伪足延伸的形成。总体神经元群体的形态成熟度未受影响。总之，我们的数据表明，GDNF是小脑皮质传出神经元浦肯野细胞的一种有效的存活和分化因子。连同其其他作用，这些发现增加了GDNF可能是控制运动功能的神经回路中多个位点的关键营养因子的可能性。
