Postnatal Development of High Affinity Neuronal Recognition Sites for ³H-5-HT in Rat Brain

Abstract

The postnatal development of ³H-5-HT specific binding sites has been studied in rat brain. Experimental conditions allowed the characterization of the class of sites corresponding to the synaptosomal receptor for 5-HT. The related affinity constant and maximal binding were measured at various ages after birth. During the second week after birth, the serotonin receptor system developed explosively, the maximal number of sites increasing from a nonsignificant value to that observed in adult rats. Lesion of the presynaptic neurons using 5,6-DHT led to a significant increase of the number of sites.

Serotonergic receptors in the brain of in utero undernourished rats

“…Accumulated evidence suggests that during embryogenesis 5-HT acts as a differentiation signal for serotonergic neurons and their target cells by activating appropriate receptors (Azmitia, 2001;Gromová et al, 1983;Haydon et al, 1987;Lauder and Krebs, 1978). We know already that 5-HT is released from developing serotonergic neurons (Mercado et al, 1998) and that it interacts with 5-HT receptors modulating their expression (Fillion et al, 1982;Mercado and Hernandez-R, 1992;Mercado et al, 1998;Morilak and Ciaranello, 1993;Whitaker-Azmitia, 1991); some studies have identified various 5-HT receptor subtypes during mid-gestation, including 5-HT 1A , 5-HT 2A, 5-HT 2B , and 5-HT 2C , which could mediate the effects of serotonin during brain development (Bolaños et al, 1997;Davidson and Stamford, 1995;Duncan et al, 2000;Morilak and Ciaranello, 1993;Nebigil et al, 2001;O'Connor and Kruk, 1992), as observed in this study for 5-HT 1A and 5-HT 1B receptors. The presence of 5-HT 1A in axonal growth cones suggest their involvement in the signaling processes related to axogenesis and synaptogenesis (Bar et al, 1991;Lauder et al, 2000;Mercado et al, 1998).…”

“…Membranes from homogenates were obtained as previously described by Fillion et al (1982). Enriched fractions with neurons were isolated from brainstem according to Rose (1967).…”

“…Synaptosomes of cerebral cortex were prepared following the method of Kurokawa et al (1965). AGCP were isolated from fetal brain according to Pfenninger et al (1983), modified by Mercado and Hernandez-R (1994).For binding experiments, the procedure described by Fillion et al (1982) was used. Membranes from homogenates were incubated for 3 min with 10 M GTP in 0.05 M Tris-HCl, pH 7.40, with 0.1 mM pargyline and 0.01% ascorbic acid, and subsequently for 10 min with [3H] 5-HT (27.5 Ci/mmol, DuPont Nensure; concentration range: 1-6 nM), at 22 • C. A curve of blanks was run with an excess of unlabeled 5-HT (10 M).…”

“…5-Hydroxytryptamine (5-HT, serotonin) has been implicated in regulating brain development prior to the time it assumes its role as neurotransmitter in the mature brain (Choi et al, 1998;Gromová et al, 1983;Haydon et al, 1987;Lauder and Krebs, 1978;Mercado and Hernandez-R, 1992;Mercado et al, 1998;Whitaker-Azmitia, 1991). During the fetal period, 5-HT is involved in the processes of neuronal growth and differentiation: axogenesis (Haydon et al, 1987;Mercado and Hernandez-R, 1992;Mercado et al, 1998), maturation of target neurons (Lauder and Krebs, 1978), final number of specific 5-HT receptors (Fillion et al, 1982) and modulation of its own synthesis (Nebigil et al, 2001). As a neurotransmitter in the adult brain, 5-HT is involved in the control of numerous physiologic functions (food intake, temporal control, sleep patterns, nociception) (Jouvet, 1999;Oscos and Hernandez-R, 1982;Randic and Yu, 1976;Shor-Posner et al, 1986) as well as in some psychiatric disorders such as anxiety and depression (Mann, 1999).…”

Magnetic field exposure during gestation: pineal and cerebral cortex serotonin in the rat

“…A good model to study the effect of ELF on cells under intense transformation is the embryonic and the early postnatal growth period (Cameron et al, 1993;Yang et al, 1992;Ho et al, 1992;Moses and Martin, 1992;Martin, 1992;Wiley et al, 1992;Husskoen and Koulainen, 1993;Frolen et al, 1993;Sakamoto et al, 1993). In the rat brain serotonin synapses are under intense and continuous growth during the first 2 weeks of postnatal development and serotonin (5-HT) content parallel this increase (Fillion et al, 1982;Zifa et al, 1980;Hernández et al, 1984). This preliminary report describes the effect of ELF on the 5-HT content of the cerebral cortex of normal growing offsprings of Wistar rats exposed during pregnancy to ELF.…”