Golden J P, Baloh R H, Kotzbauer P T, Lampe P A, Osborne P A, Milbrandt J, Johnson E M
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Comp Neurol. 1998 Aug 17;398(1):139-50. doi: 10.1002/(sici)1096-9861(19980817)398:1<139::aid-cne9>3.0.co;2-2.
Neurturin (NTN) and glial cell line-derived neurotrophic factor (GDNF) are the first two members of the GDNF family (GF) of neurotrophic factors. These two proteins are potent survival factors for several populations of central and peripheral neurons in mature and developing rodents. The receptor for these factors is a multicomponent complex that includes the RET (rearranged during transfection) tyrosine kinase receptor and one of two glycosyl phosphatidylinositol (GPI)-linked ligand-binding components called GDNF family receptor alphas (GFRalpha-1 and GFRalpha-2). We have used in situ hybridization to study the mRNA expression of NTN, GDNF, RET, GFRalpha-1, and GFRalpha-2 in the central nervous system (CNS) of adult mice. GF receptors are expressed in several areas in which neuronal populations known to respond to NTN and GDNF are located, including the ventral horn of the spinal cord and the compacta region of the substantia nigra. In addition, we have demonstrated receptor expression in other areas of the brain including the thalamus and hypothalamus. Neurons in these areas express GF receptors, and therefore, may respond to NTN or GDNF. NTN and GDNF are expressed in targets of neurons that express GF receptors. The pattern of GF factor and receptor expression in the adult brain suggests a role for these factors in maintaining neuronal circuits in the mature CNS.
神经营养因子（NTN）和胶质细胞系源性神经营养因子（GDNF）是神经营养因子GDNF家族（GF）的前两个成员。这两种蛋白质是成熟和发育中的啮齿动物体内几种中枢和外周神经元群体的有效存活因子。这些因子的受体是一种多组分复合物，包括RET（转染时重排）酪氨酸激酶受体以及两种糖基磷脂酰肌醇（GPI）连接的配体结合成分之一，称为GDNF家族受体α（GFRα-1和GFRα-2）。我们利用原位杂交技术研究了成年小鼠中枢神经系统（CNS）中NTN、GDNF、RET、GFRα-1和GFRα-2的mRNA表达情况。GF受体在已知对NTN和GDNF有反应的神经元群体所在的几个区域表达，包括脊髓腹角和黑质致密部。此外，我们还证明了在大脑的其他区域，包括丘脑和下丘脑也有受体表达。这些区域的神经元表达GF受体，因此可能对NTN或GDNF有反应。NTN和GDNF在表达GF受体的神经元的靶标中表达。成年大脑中GF因子和受体的表达模式表明这些因子在维持成熟中枢神经系统中的神经元回路方面发挥作用。
