Winkler J, Thal L J
Department of Neurosciences, University of California, San Diego 92093, USA.
Exp Neurol. 1995 Dec;136(2):234-50. doi: 10.1006/exnr.1995.1100.
Rats with bilateral lesions of the nucleus basalis magnocellularis (NBM) produced by ibotenic acid (IBO), quisqualic acid (QUIS), and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) received either human recombinant nerve growth factor (NGF) (5.0 micrograms/day) or cytochrome c (cc) (0.3 microgram/day) treatment. Spatial memory impairments in the Morris water maze differed for the three toxins in the following order: IBO-cc > AMPA-cc > QUIS-cc. Treatment with NGF resulted in behavioral improvement for only the IBO-lesioned rats. Body weight was not affected by the different lesions before treatment; however, administration of NGF resulted in a decreased rate of body weight gain independent of the excitotoxin used. Reduction in choline acetyltransferase (ChAT) activity differed in the neocortex for the three toxins, whereas the hippocampus was unaffected. The cortical ChAT depletion was greatest for AMPA, intermediate for QUIS, and least for IBO. Restoration of ChAT activity by NGF differed for the three toxins (QUIS-NGF > IBO-NGF > AMPA-NGF), whereas ChAT activity in the hippocampus was increased equally. The loss of low-affinity NGF-receptor (p75NGFr)-immunoreactive neurons differed for the toxins (AMPA-cc > QUIS-cc > IBO-cc), whereas treatment with NGF increased the size of the remaining neurons independently of the used toxin. NGF induced a p75NGFr-immunoreactive thickening around intracerebral arteries for all three toxins. Lesions of the NBM produced by IBO, QUIS, and AMPA resulted in a quantitatively different pattern of behavioral, biochemical, and histological deficits. The quantitatively different pattern of recovery after administration of NGF may be determined by the responsivity of the remaining neurons. Intracerebroventricular administration of NGF affected noncholinergic systems as well, resulting in decreased food intake and cerebrovascular hyperinnervation.
用鹅膏蕈氨酸（IBO）、喹啉酸（QUIS）和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）造成双侧基底大细胞核（NBM）损伤的大鼠，分别接受人重组神经生长因子（NGF）（5.0微克/天）或细胞色素c（cc）（0.3微克/天）治疗。在莫里斯水迷宫中，三种毒素导致的空间记忆损伤情况如下：IBO-cc＞AMPA-cc＞QUIS-cc。只有IBO损伤的大鼠接受NGF治疗后行为得到改善。治疗前，不同损伤对体重没有影响；然而，无论使用何种兴奋性毒素，给予NGF都会导致体重增加速率降低。三种毒素导致新皮质中胆碱乙酰转移酶（ChAT）活性降低的情况不同，而海马体不受影响。AMPA导致的皮质ChAT耗竭最大，QUIS次之，IBO最小。三种毒素经NGF恢复ChAT活性的情况不同（QUIS-NGF＞IBO-NGF＞AMPA-NGF），而海马体中的ChAT活性同等增加。低亲和力NGF受体（p75NGFr）免疫反应性神经元的损失因毒素而异（AMPA-cc＞QUIS-cc＞IBO-cc），而NGF治疗使剩余神经元的体积增大，与所用毒素无关。对于所有三种毒素，NGF均诱导脑内动脉周围出现p75NGFr免疫反应性增厚。IBO、QUIS和AMPA造成的NBM损伤导致行为、生化和组织学缺陷的数量模式不同。给予NGF后恢复的数量模式差异可能由剩余神经元的反应性决定。脑室内给予NGF也会影响非胆碱能系统，导致食物摄入量减少和脑血管神经支配过度。
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