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  • Title: 5,7-Dihydroxytryptamine induced changes in the postnatal development of central 5-hydroxytryptamine neurons.
    Author: Sachs C, Jonsson G.
    Journal: Med Biol; 1975 Jun; 53(3):156-64. PubMed ID: 1160409.
    Abstract:
    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.
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