Postnatal development of bulbospinal serotoninergic system. effects of GMI ganglioside following neonatal 5,7-dihydroxytryptamine treatment.

The postnatal development of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the pons medulla and spinal cord segments of rats treated with 5,7-dihydroxytryptamine (5,7-HT) and/or GM1 ganglioside has been investigated. Animals have been sacrificed at 4, 7, 28 and 56 days of age. In control rats, 5-HT and 5-HIAA increase in all areas during the first postnatal week. Thereafter, 5-HT and 5-HIAA remain constant in the thoracic and lumbar segments while a further increment takes place in the cervical portion. In the pons medulla, 5-HT reaches a plateau at 28 days, while 5-HIAA reaches a peak at 7 days and then declines to the adult value at 28 days. Neonatal administration of 5,7-HT produces mixed-type alterations in the developing bulbospinal serotoninergic system. Whilst 5-HT and 5-HIAA markedly decrease in the most distal 5-HT nerve terminal projections (thoracic and lumbar cord) they increase in the pons medulla ("pruning effect"). These alterations are accompanied by regional variations of the 5-HIAA/5-HT ratio, an index of 5-HT turnover. In particular, a prominent decrease of 5-HIAA/5-HT occurs in the lumbar segment of 1- and 2-month-old rats. In this area, where the effect of 5,7-HT is the most severe, an "up-regulation" of 5-HT, receptors is observed in 2-month-old rats. GM1 administration does not modify the development of the bulbospinal serotoninergic system. However, GM1 treatment has a counteracting effect on the alterations induced by 5,7-HT. Recovery of 5-HT and 5-HIAA levels occurs in the thoracic and lumbar cord of 1- and 2-month-old rats and is paralleled by a reduction of the "pruning effect" in the pons medulla. Furthermore, in the lumbar cord of 2-month-old rats, GM1 prevents the decrease of the 5-HIAA/5-HT ratio and the "up-regulation" of 5-HT(l) receptors induced by the neurotoxin. It is suggested that the GM1 effect is due to a prevention of the retrograde axonal degeneration occurring after the lesion and/or a growth stimulation of injured axons.