Rossner S, Wörtwein G, Gu Z, Yu J, Schliebs R, Bigl V, Perez-Polo J R
Department of Neurochemistry, Paul Flechsig Institute for Brain Research, Leipzig, Germany.
J Neurochem. 1997 Sep;69(3):947-53. doi: 10.1046/j.1471-4159.1997.69030947.x.
It is well documented that nerve growth factor (NGF) plays an important role in maintaining functions of cholinergic basal forebrain neurons. In the present study, we tested the hypothesis that cholinergic activity controls NGF levels in cholinoceptive neurons of the cerebral cortex and hippocampus. To address that question, we used both cholinergic deafferentation of cerebral cortex and hippocampus by cholinergic immunolesion with 192IgG-saporin and chronic pharmacological treatment of sham-treated and immunolesioned rats with the cholinergic agonist pilocarpine and the cholinergic antagonist scopolamine. We observed an increase in NGF protein levels in the cortex and hippocampus after cholinergic immunolesions and also after muscarinic receptor blockade by chronic intracerebroventricular scopolamine infusion in sham-treated rats after 2 weeks. There was no further increase in the accumulation of NGF after scopolamine treatment of immunolesioned rats. Chronic infusion of pilocarpine had no effect on cortical and hippocampal NGF protein levels in sham-treated rats. In rats with cholinergic immunolesions, however, pilocarpine did prevent the lesion-induced accumulation of NGF. There was no effect of cholinergic lesion and drug treatment on cortical or hippocampal NGF mRNA levels, consistent with the importance of NGF retrograde transport as opposed to its de novo synthesis. This study provides strong evidence for the hypothesis that there is cholinergic control of cortical and hippocampal NGF protein but not mRNA levels in adult rats.
有充分的文献记载，神经生长因子（NGF）在维持胆碱能基底前脑神经元的功能中起重要作用。在本研究中，我们检验了这样一个假设，即胆碱能活性控制大脑皮层和海马体中胆碱能感受神经元的NGF水平。为了解决这个问题，我们采用了两种方法：通过用192IgG-皂草素进行胆碱能免疫损伤对大脑皮层和海马体进行胆碱能去传入，以及用胆碱能激动剂毛果芸香碱和胆碱能拮抗剂东莨菪碱对假手术组和免疫损伤组大鼠进行慢性药物治疗。我们观察到，在胆碱能免疫损伤后，以及在假手术组大鼠经2周脑室注射东莨菪碱进行慢性毒蕈碱受体阻断后，大脑皮层和海马体中的NGF蛋白水平有所增加。对免疫损伤大鼠进行东莨菪碱治疗后，NGF的积累没有进一步增加。在假手术组大鼠中，慢性注射毛果芸香碱对大脑皮层和海马体中的NGF蛋白水平没有影响。然而，在胆碱能免疫损伤的大鼠中，毛果芸香碱确实能阻止损伤诱导的NGF积累。胆碱能损伤和药物治疗对大脑皮层或海马体中的NGF mRNA水平没有影响，这与NGF逆行运输的重要性相一致，而不是其从头合成。本研究为成年大鼠大脑皮层和海马体中存在胆碱能对NGF蛋白而非mRNA水平的控制这一假设提供了有力证据。
