Casamenti F, Di Patre P L, Milan F, Petrelli L, Pepeu G
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
Neurosci Lett. 1989 Aug 14;103(1):87-91. doi: 10.1016/0304-3940(89)90490-4.
Four groups of rats with a unilateral ibotenic acid lesion of the nucleus basalis were treated with saline, nerve growth factor (NGF) 10 micrograms administered intracerebroventricularly twice per week, sialoganglioside GM1 30 m/kg daily i.p. and NGF twice per week plus GM1 10 mg/kg i.p. daily, respectively, beginning immediately after lesioning. Twenty-one days later the rats treated with saline showed a marked impairment in negotiating a 'step through' passive avoidance conditioned response, a 32% decrease in the number of choline acetyltransferase (ChAT)-positive neurons in the lesioned nucleus basalis and a 12% decrease in their areas. The rats treated with NGF and NGF plus GM1 showed no difference from sham-operated rats. In the GM1-treated rats a 12% decrease only in the number of ChAT-positive neurons was detected while performance and neuronal areas were normal. These findings indicate that NGF and GM1 prevent the cholinergic deficit by protecting the cholinergic neurons of the nucleus basalis from ibotenic acid neurotoxicity.
四组患有基底核单侧鹅膏蕈氨酸损伤的大鼠,分别在损伤后立即开始接受如下处理:生理盐水处理;每周两次脑室内注射10微克神经生长因子(NGF);每天腹腔注射30毫克/千克唾液酸神经节苷脂GM1;每周两次脑室内注射NGF加每天腹腔注射10毫克/千克GM1。21天后,接受生理盐水处理的大鼠在“穿梭箱”被动回避条件反应测试中表现出明显受损,损伤的基底核中胆碱乙酰转移酶(ChAT)阳性神经元数量减少32%,其面积减少12%。接受NGF处理以及接受NGF加GM1处理的大鼠与假手术大鼠相比无差异。在接受GM1处理的大鼠中,仅检测到ChAT阳性神经元数量减少12%,而行为表现和神经元面积均正常。这些发现表明,NGF和GM1通过保护基底核的胆碱能神经元免受鹅膏蕈氨酸神经毒性,从而预防胆碱能缺陷。