Expanded distribution of mRNA for nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 in the rat brain after colchicine treatment.

The effect of intracerebroventricular injection of the mitosis inhibitor colchicine on expression of mRNA for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 was studied in the rat brain with in situ hybridization. Colchicine up-regulates mRNA for NGF and BDNF in many of the neuronal systems normally expressing these factors. In addition, after colchicine treatment NGF and BDNF mRNAs were localized in several brain areas where they normally cannot be detected. Thus, NGF mRNA was present, for example, in many motor nuclei and in the basal forebrain, and BDNF mRNA was seen in many nuclei in the brain stem and in catecholamine neurons, including dopamine neurons in the substantia nigra. The latter neurons have recently been shown to be sensitive to BDNF, and the present results show that these neurons can produce this factor themselves. A decrease in mRNA for BDNF and neurotrophin 3 was seen only in the granular-cell layer of the hippocampal formation. A strong hybridization signal for BDNF and neurotrophin 3 mRNA was also observed over several myelinated tracts in treated rats, supporting the hypothesis that glial cells as well as neurons can produce these trophic factors. IMAGES:

本研究采用原位杂交技术，探究了脑室内注射有丝分裂抑制剂秋水仙素对大鼠脑内神经生长因子（nerve growth factor, NGF）、脑源性神经营养因子（brain-derived neurotrophic factor, BDNF）以及神经营养因子3（neurotrophin 3）的mRNA表达水平的影响。秋水仙素可上调多种正常表达此类因子的神经元系统中NGF与BDNF的mRNA表达量。此外，经秋水仙素处理后，NGF与BDNF的mRNA可在多个正常情况下无法检测到该类转录本的脑区中被定位检出。例如，NGF mRNA可在诸多运动神经核团以及基底前脑中检测到；BDNF mRNA则可见于脑干内的多个神经核团以及儿茶酚胺能神经元，包括黑质多巴胺能神经元。近期已有研究证实，此类神经元对BDNF具有敏感性，而本研究结果表明，这些神经元可自主合成该营养因子。仅在海马结构的颗粒细胞层中，可观察到BDNF与神经营养因子3的mRNA水平出现下调。经处理的大鼠体内，多条有髓神经束上也可检测到BDNF与神经营养因子3 mRNA的强杂交信号，这一结果支持"胶质细胞与神经元均可合成此类营养因子"的假说。图像：