Pharmacological stimulation reveals recombinant human nerve growth factor-induced increases of in vivo hippocampal cholinergic function measured in rats with partial fimbrial transections.
Pharmacological stimulation reveals recombinant human nerve growth factor-induced increases of in vivo hippocampal cholinergic function measured in rats with partial fimbrial transections.
复制标题
药理学刺激揭示了重组人神经生长因子诱导的体内海马胆碱能功能的增加，这是在部分伞毛横断的大鼠中测量的。
DOI：
10.1016/0306-4522(92)90208-j
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发表时间：
1992
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;Jenden,DJ;Hefti,F
The present study determined the effects of chronic recombinant human nerve growth factor administration [1 μg given intracerebroventricularly q.i.d. (every other day) for three weeks] onin vivohippocampal cholinergic function in adult rats with unilateral partial fimbrial transections. Partial fimbrial transections did not significantly alter the levels of endogenous acetylcholine or [2H4]acetylcholine in the hippocampus due to functional compensation by surviving cholinergic terminals. In animals chronically treated with nerve growth factor, the levels of endogenous choline, endogenous acetylcholine, [2H4]choline and [2H4]acetylcholine accumulated in the hippocampus on the lesioned side were not significantly different from those on the contralateral unlesioned side or from values measured in animals treated with cytochrome c, a control protein. However, changes in cholinergic parameters induced by the partial lesions or recombinant human nerve growth factor treatment became manifest when animals were challenged using pharmacological agents such as pentylenetetrazole or pilocarpine given after lithium chloride pretreatment. First, in nerve growth factor-treated animals administered the general stimulant pentylenetetrazole (10 mg/kg) 2 min prior to measuringin vivocholinergic parameters, we observed a significant increase in the hippocampal content of [2H4]choline in both lesioned and unlesioned hippocampi. The magnitude of the increase was significantly higher on the lesioned compared to the unlesioned side. Although chronic recombinant human nerve growth factor treatment induced increases of hippocampal [2H4]choline levels, there were no concomitant increases in the level of [2H4]acetylcholine. Second, in nerve growth factor-treated animals administered lithium chloride (3 mmol/kg) 20 h prior to pilocarpine (30 mg/kg), we observed a significant enhancement of the content of endogenous acetylcholine in the hippocampus of the lesioned side. Partial fimbrial transections also reducedin vitrocholinergic parameters reflecting endogenous acetylcholine levels in hippocampal slices. The content of endogenous acetylcholine in the slices was decreased by approximately 50% and chronic nerve growth factor treatment significantly elevated this value to approximately non-lesioned control values. Similarly, reductions in spontaneous and veratridine-evoked release of endogenous acetylcholine induced by partial fimbrial transections were counteracted by recombinant human nerve growth factor treatment.These findings demonstrate that chronic recombinant human nerve growth factor treatment effectively enhances thein vivoandin vitrosynthesis, storage and release of endogenous acetylcholine. The results from thein vivostudies suggest that recombinant human nerve growth factor-induced differences in functional performance of hippocampal neurons may only be manifest during behavioral and/or pharmacological stimulation.
