Glial cell line-derived neurotrophic factor sustains axotomized basal forebrain cholinergic neurons in vivo: dose-response comparison to nerve growth factor and brain-derived neurotrophic factor.
Glial cell line-derived neurotrophic factor sustains axotomized basal forebrain cholinergic neurons in vivo: dose-response comparison to nerve growth factor and brain-derived neurotrophic factor.
复制标题
DOI：
--
复制
发表时间：
1996-05
期刊：
影响因子：
--
通讯作者：
L. R. Williams;G. Inouye;V. Cummins;M. Pelleymounter
中科院分区：
文献类型：
--
作者：
L. R. Williams;G. Inouye;V. Cummins;M. Pelleymounter
将胶质细胞源性神经营养因子（GDNF）连续2周注入已接受单侧穹窿海马伞切割术的雄性Wistar大鼠的脑室。在溶剂处理，对照组动物，有一个70%的损失胆碱乙酰转移酶（ChAT）阳性和60%的损失p75阳性神经元在隔/斜角带同侧的轴突切断确定的免疫组织化学，没有损失的ChAT生化活性。GDNF治疗10微克/天完全防止了p75阳性神经元的损失，显着减少ChAT阳性神经元的损失到正常的40%，刺激ChAT生化活性比正常的40%以上，轴突切断依赖的方式。GDNF的效力比NGF低1个数量级，但与NGF不同，GDNF对正常的未损伤神经元几乎没有影响。GDNF比BDNF强1个数量级，BDNF对ChAT生化活性无影响。GDNF和NGF抑制体重增加，而BDNF在100微克/天的剂量下诱导显著的体重减轻和死亡。
Glial cell line-derived neurotrophic factor (GDNF) was infused continuously for 2 weeks into the ventricles of male Wistar rats that had received a unilateral knife transection of the fimbria/fornix. In vehicle-treated, control animals, there was a 70% loss of choline acetyltransferase (ChAT)-positive and a 60% loss of p75-positive neurons in the septum/diagonal band ipsilateral to the axotomy as identified by immunohistochemistry, with no loss in ChAT biochemical activity. GDNF treatment at 10 micrograms/day completely prevented the loss of p75-positive neurons, significantly reduced the loss of ChAT-positive neurons to 40% of normal, and stimulated ChAT biochemical activity to 40% more than normal in an axotomy-dependent manner. GDNF is 1 order of magnitude less potent than NGF but, unlike NGF, had little or no effect on normal, uninjured neurons. GDNF was 1 order of magnitude more potent than BDNF, and BDNF had no effect on ChAT biochemical activity. GDNF and NGF inhibited weight gain, whereas BDNF induced significant weight loss and death at the dosage of 100 micrograms/day.