EFFECTS OF THE NORADRENALINE NEUROTOXIN DSP4 ON THE POSTNATAL-DEVELOPMENT OF CENTRAL NORADRENALINE NEURONS IN THE RAT
EFFECTS OF THE NORADRENALINE NEUROTOXIN DSP4 ON THE POSTNATAL-DEVELOPMENT OF CENTRAL NORADRENALINE NEURONS IN THE RAT
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DOI：
10.1016/0306-4522(82)90112-9
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发表时间：
1982-01-01
期刊：
影响因子：
3.3
通讯作者：
SUNDSTROM, E
中科院分区：
文献类型：
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作者：
JONSSON, G;HALLMAN, H;SUNDSTROM, E
采用神经化学方法研究了去甲肾上腺素神经毒素DSP4对大鼠出生后中枢去甲肾上腺素能神经元发育的影响。DSP4对蓝斑去肾上腺素能神经元系统有优先作用，对多巴胺和肾上腺素神经元无明显影响，对5-羟色胺（5-羟色胺，5-HT）神经元有轻微的神经毒性作用。摄取阻断剂zimelidine预处理可以完全阻断DSP4对5-HT神经元的作用，且不影响DSP4对去甲肾上腺素能神经元的作用。新生儿DSP4治疗系统性地导致大脑皮层和脊髓内NE的永久性消耗，小脑和脑桥延髓内NE的显著增加。DSP4的这些作用是剂量依赖性的，可以通过NE摄取阻滞剂地西帕明预处理来阻断。内源性NE水平的变化在数量上与体外切片中[3H]NE摄取的变化相似。新生儿DSP4治疗后，在分析整个中枢神经系统时，这些去甲肾上腺素能参数没有显著变化，尽管在两个方向上都有显著的局部变化。给不同年龄的大鼠注射DSP4，在所有发育阶段的所有区域，包括脑桥髓质和小脑，都产生了急性显著的NE消耗。在所有年龄的大鼠治疗后，远端去肾上腺素能神经末梢突起中都发现了显著的和永久性的NE消耗，而在3-5天的大鼠中，仅在DSP4治疗的大鼠中观察到脑桥髓质和小脑中NE水平的增加。在老年大鼠中给予DSP4可导致两个区域NE的大量和永久性消耗。3-5日龄大鼠治疗后去甲肾上腺素能神经元出生后发育的改变主要与DSP4的修剪作用有关，DSP4阻止远端神经末梢突起的发育，导致未受神经毒素影响的侧枝系统神经的生长增加。DSP4可能是研究发育中的蓝斑神经元各方面去肾上腺素能神经传递的一个有用的去神经控制工具。
The effect of the noradrenaline [norepinephrine, NE] neurotoxin DSP4 [N-2-chloroethyl-N-ethyl-2-bromobenzylamine] on the postnatal development of central noradrenergic neurons in the rat was investigated using neurochemical techniques. A preferential effect of DSP4 on the locus coeruleus noradrenergic neuron system without any notable effects on the dopamine and adrenaline [epinephrine] neurons and only a minor neurotoxic effect on the serotonin [5-hydroxytryptamine, 5-HT] neurons were demonstrated. The effect of DSP4 on the 5-HT neurons could be completely prevented by pretreatment with the uptake blocker zimelidine, without affecting the action of DSP4 on noradrenergic neurons. Neonatal DSP4 treatment systemically led to permanent depletions of NE in the cerebral cortex and spinal cord and marked increases of NE in the cerebellum and pons medulla. These effects of DSP4 were dose-dependent and could be blocked by pretreatment with the NE uptake blocker desipramine. The alterations in endogenous NE levels were quantitatively similar to changes observed in [3H]NE uptake in slices in vitro. There were no significant changes of these noradrenergic parameters when analyzing the whole CNS after neonatal DSP4 treatment in spite of marked regional changes in both directions. Administration of DSP4 to rats of different ages produced acutely marked depletions of NE in all regions including the pons medulla and the cerebellum at all developmental stages. Marked and permanent depletions of NE were found in the distant noradrenergic nerve terminal projections after treatment at all ages, whereas increases in NE levels in the pons medulla and cerebellum were only observed in rats treated with DSP4 up to the age of 3-5 days. A DSP4 administration in older rats led to substantial and permanent depletions of NE in both regions. The alteration of the postnatal development of noradrenergic neurons after treatment of rats up to the age of 3-5 days is mainly related to a pruning effect of DSP4, in which prevention of the development of distant nerve terminal projections causes an increased outgrowth of nerves in collateral systems spared by the neurotoxin. DSP4 may be a useful denervation tool for studying various aspects of noradrenergic neurotransmission of developing locus coeruleus neurons.