Williams L R, Rylett R J
CNS Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001.
J Neurochem. 1990 Sep;55(3):1042-9. doi: 10.1111/j.1471-4159.1990.tb04594.x.
The objective of this study was to determine the effect of age and chronic intracerebral administration of nerve growth factor (NGF) on the activity of the presynaptic cholinergic neuronal markers hemicholinium-sensitive high-affinity choline uptake (HACU) and choline acetyltransferase (ChAT) in the brain of Fisher 344 male rats. In 24-month-old rats, a substantial decrease in ChAT activity (30%) was measured in striatum, and decreases in HACU were found in frontal cortex (28%) and hippocampus (23%) compared with 4-month-old controls. Cholinergic neurons in brain of both young adult and aged rats responded to administration of exogenous NGF by increased expression of both phenotypes. In 4-month-old animals, NGF treatment at 1.2 micron/day resulted in increased activities of both ChAT and HACU in striatum (175 and 170%, respectively), frontal cortex (133 and 125%), and hippocampus (137 and 125%) compared with untreated and vehicle-treated 4-month-old animals; vehicle treatment had no effect on the activity of either marker. In 24-month-old animals treated with NGF for 2 weeks, ChAT activity was increased in striatum (179%), frontal cortex (134%), and hippocampus (119%) compared with 24-month-old control animals. Synaptosomal HACU in 24-month-old rats was increased in striatum (151%) and frontal cortex (128%) after 2 weeks of NGF treatment, but hippocampal HACU was not significantly different from control values.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究的目的是确定年龄以及长期脑内注射神经生长因子(NGF)对Fisher 344雄性大鼠脑内突触前胆碱能神经元标志物——半胱氨酸敏感的高亲和力胆碱摄取(HACU)和胆碱乙酰转移酶(ChAT)活性的影响。与4月龄对照组相比,24月龄大鼠纹状体中的ChAT活性显著降低(30%),额叶皮质(28%)和海马体(23%)中的HACU降低。年轻成年大鼠和老年大鼠脑内的胆碱能神经元对外源性NGF的给药均有反应,两种表型的表达均增加。在4月龄动物中,与未治疗和接受载体治疗的4月龄动物相比,每天1.2微克的NGF治疗使纹状体(分别为175%和170%)、额叶皮质(133%和125%)和海马体(137%和125%)中的ChAT和HACU活性增加;载体治疗对任何一种标志物的活性均无影响。在接受2周NGF治疗的24月龄动物中,与24月龄对照动物相比,纹状体(179%)、额叶皮质(134%)和海马体(119%)中的ChAT活性增加。在24月龄大鼠中,经2周NGF治疗后,纹状体(151%)和额叶皮质(128%)中的突触体HACU增加,但海马体HACU与对照值无显著差异。(摘要截选至250字)