Sachs C, Jonsson G
Med Biol. 1975 Jun;53(3):156-64.
Systemic administration of the neurotoxic compound 5,7-dihydroxytryptamine (5,7-HT) to newborn rats led acutely (within 1--2 h) to a marked reduction of the in vitro uptake of [3H]5-hydroxytryptamine (5-HT) in homogenates from the cerebral cortex (75% decrease) and the pons-medulla (60% decrease). When 5,7-HT was administered postnatally we found that between days 5 an7 resistance developed in the cerebral cortex towards the 5,7-HT induced reduction in 3H-5-HT uptake. This was most likely the result of the postnatal development of the blood-brain barrier. These results show that 5,7-HT can pass the blood-brain barrier in the neonate stage and enter the brain to exert its well-known neurotoxic action on 5-HT neurons. The [3H]5-HT uptake in the cerebral cortex was reduced quantitatively to the same extent up to the 28th postnatal day, after which time a moderate recovery took place. Endogenous 5-HT was reduced by 40% in the cerebral cortex when measured in adult animals. In the pons-medulla there was a rapid recovery of the [3H]5-HT uptake during the first week after the 5,7-HT treatment and on the 14th postnatal day the increase was as much as 75% compared with the control. Endogenous 5-HT and [3H]5-HT uptake was increased by 40--50% when the analysis was performed 2 months after the 5,7-HT treatment. Studies of [3H]noradrenaline (NA) uptake after 5,7-HT administration at birth showed that this treatment similarly affected the NA neurons, though to a lesser extent. The effects on the NA neurons could be abolished by pretreatment with the "membrane pump" blocker desipramine, leaving the action of 5,7-HT on 5-HT neurons almost unaffected. Analysis of the [3H]5-HT uptake kinetics in the pons-medulla showed that the 5,7-HT treatment did not affect the Km while the Vmax was increased. It is concluded that neonatal 5,7-HT treatment produces a marked 5-HT denervation of the cerebral cortex, while there is a stimulated postnatal outgrowth of 5-HT nerve terminals in the pons-medulla, after an initial partial damage of the neurons.
对新生大鼠全身给予神经毒性化合物5,7 - 二羟基色胺（5,7 - HT），在急性（1 - 2小时内）导致大脑皮层（降低75%）和脑桥 - 延髓（降低60%）匀浆中[3H]5 - 羟色胺（5 - HT）的体外摄取显著减少。当在出生后给予5,7 - HT时，我们发现出生后第5至7天，大脑皮层对5,7 - HT诱导的3H - 5 - HT摄取减少产生了抗性。这很可能是血脑屏障出生后发育的结果。这些结果表明，5,7 - HT在新生儿期可以穿过血脑屏障并进入大脑，对5 - HT神经元发挥其众所周知的神经毒性作用。大脑皮层中[3H]5 - HT摄取在出生后第28天之前定量减少到相同程度，此后有适度恢复。在成年动物中测量时，大脑皮层中内源性5 - HT减少了40%。在脑桥 - 延髓，5,7 - HT处理后第一周内[3H]5 - HT摄取迅速恢复，与对照组相比，出生后第14天增加高达75%。在5,7 - HT处理2个月后进行分析时，内源性5 - HT和[3H]5 - HT摄取增加了40 - 50%。对出生时给予5,7 - HT后[3H]去甲肾上腺素（NA）摄取的研究表明，这种处理同样影响NA神经元，尽管程度较小。对NA神经元的影响可以通过用“膜泵”阻滞剂地昔帕明预处理来消除，而5,7 - HT对5 - HT神经元的作用几乎不受影响。对脑桥 - 延髓中[3H]5 - HT摄取动力学的分析表明，5,7 - HT处理不影响Km，而Vmax增加。结论是，新生儿期5,7 - HT处理导致大脑皮层明显的5 - HT去神经支配，而在神经元最初部分受损后，脑桥 - 延髓中5 - HT神经末梢在出生后有刺激的生长。
