Effect of recombinant human nerve growth factor on presynaptic cholinergic function in rat hippocampal slices following partial septohippocampal lesions: measures of [3H]acetylcholine synthesis, [3H]acetylcholine release and choline acetyltransferase acti
Effect of recombinant human nerve growth factor on presynaptic cholinergic function in rat hippocampal slices following partial septohippocampal lesions: measures of [3H]acetylcholine synthesis, [3H]acetylcholine release and choline acetyltransferase acti
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重组人神经生长因子对部分间隔海马损伤后大鼠海马切片突触前胆碱能功能的影响:[3H]乙酰胆碱合成、[3H]乙酰胆碱释放和胆碱乙酰转移酶活性的测量
DOI:
10.1016/0306-4522(91)90033-k
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发表时间:
1991
期刊:
影响因子:
3.3
通讯作者:
Hefti,F
中科院分区:
文献类型:
--
作者:
Lapchak,PA;Hefti,F
To determine whether intraventricular administration of nerve growth factor alters presynaptic cholinergic function in the intact hippocampus or following partial lesions of the flmbria, we investigated the effects of recombinant human nerve growth factor treatment on [3H]acetylcholine synthesis and release by hippocampal slices following various treatment regimens. For chronic nerve growth factor treatment, 1 μg of recombinant human nerve growth factor was injected intraventricularly every second day. Lesions reduced [3H]acetylcholine synthesis (by 48%) and spontaneous and evoked [3H]acetylcholine release by 35 and 61%, respectively. Chronic nerve growth factor treatment over three weeks elevated [3H]acetylcholine synthesis (by 39%) and spontaneous and evoked [3H]acetylcholine release by 27 and 64%, respectively, over values in lesioned hippocampi of animals treated with a control protein (cytochrome c). The nerve growth factor-induced enhancement of presynaptic cholinergic function persisted for three weeks following the termination of nerve growth factor administration. Furthermore, chronic (nine-week) treatment with nerve growth factor increased [3H]acetylcholine by 118% over values in lesioned hippocampi of animals treated with cytochrome c. These findings indicate that chronic treatment with recombinant human nerve growth factor increases the capacity of hippocampal cholinergic neurons surviving a partial fimbrial transection to synthesize, store and release acetylcholine. Application of recombinant human nerve growth factor during the initial weeks after lesioning was necessary to produce significant elevations in acetylcholine synthesis, since chronic recombinant human nerve growth factor treatment after delays of three or more weeks were ineffective. Furthermore, chronic nerve growth factor treatment failed to stimulate acetylcholine synthesis and release in intact hippocampal cholinergic systems. Single intraventricular injections of recombinant human nerve growth factor at the time of lesioning resulted in a small decrease in acetylcholine synthesis which, however, was not accompanied by a change in the rate of evoked acetylcholine release from cholinergic neurons surviving the lesion.The study indicates that chronic or repeated administration of nerve growth factor during the onset of degenerative events is necessary for the stimulation of presynaptic cholinergic function in the hippocampus of adult rats with partial fimbrial transactions.