Pre- and postnatal lead exposure affects the serotonergic system in the immature rat brain

Summary The effect of pre- and postnatal lead exposure on the development of the serotonergic system in striatum and brain stem was investigated. Serotonin and its metabolite 5-HIAA where determined by HPLC-EC. A significant decrease of 5-HT was detected in the brain stem at postnatal day 28. At both days 6 and 28 postnatal, 5-HIAA was reduced in striatum and brain stem. The results provide support to the hypothesis that developing 5-HT neurons are sensitive to relatively low levels of lead exposure.     

Serotonin and 5-hydroxyindoleacetic acid concentrations in individual hypothalamic nuclei and other brain areas of rat

Summary Serotonin and 5-hydroxyindoleacetic acid (5-HIAA) were measured in individual nuclei of rat hypothalamus and other brain areas using HPLC with electrochemical detection. 5-HIAA levels were first demonstrated in hypothalamic and some discrete brain areas. The 5-HIAA/5-HT ratio was highest in the n. caudatus putamen, high in the n. ventromedialis and lowest in the n. suprachiasmaticus.     

Effect of des-Tyr1-gamma-endorphin on serotonin metabolism in rat brain regions

Intracerebroventricular (i.c.v.) administration of des-Tyr1-gamma-endorphin (0.1 and 1.0 microgram) caused a decrease of the serotonin (5-HT) concentration of the hippocampus. The concentration of 5-HIAA and the pargyline-induced alterations in 5-HT and 5-HIAA were not affected. No effects were noticed in other brain regions.     

Tryptophan (Trp), serotonin (5-HT), monoamino oxidase (MAO) and 5-hydroxyindole acetic acid (5-HIAA) in brain and subesophagic ganglions of earthworms. Effects of Parathion

Summary Tryptophan, 5-HT, MAO and 5-HIAA were determined in the first 5 segments of earthworms (Oligochaetae) where the brain and subesophagic ganglions are located. Tranylcypromine (IMAO) decreased MAO activity increasing 5-HT and decreasing 5-HIAA. Motility and survival of worms were disturbed. InAllolobophora species (young worms), parathion fumigation decreased acetylcholinesterase (AChE) activity and increased Trp, 5-HT and 5-HIAA. Motility was diminished after 24 h: it worsened after 72, but returned to normal levels 40/50 days later.Publication of the National Institute of Agrarian Technology (INTA), Argentina.Acknowledgments. We are most grateful to Prof. Zlatko Tomsic (from the Lillo Institute, Tucumán) and to Leticia Alvarado (from INTA) and to Prof. Mirta P. de Matosian for earthworm classification.     

Effect of des-Tyr1-γ-endorphin on serotonin metabolism in rat brain regions

Summary Intracerebroventicular (i.c.v.) administration of des-Tyr¹-γ-endorphin (0.1 and 1.0 μg) caused a decrease of the serotonin (5-HT) concentration of the hippocampus. The concentration of 5-HIAA and the pargyline-induced alterations in 5-HT and 5-HIAA were not affected. No effects were noticed in other brain regions. Acknowledgement. The skilful technical assistance of Ms Henny de Vos Burchart-Lodewijks and Mrs H.A. Spierenburg and J.A. Meijer is gratefully acknowledged. Des-Tyr¹-γ-endorphin was a gift of Dr. H.M. Greven, Organon International B.V., Oss, The Netherlands. To whom reprint requests should be addressed.     

Serotoninergic modulation of mesolimbic and frontal cortical dopamine neurons

Potentiation of the effect of haloperidol on dopamine metabolism by the 5-HT uptake inhibitor CGP 6085 A, and antagonism of this effect by the 5-HT antagonist mianserin were observed in the mesolimbic area and the frontal cortex of the rat brain. A similar effect was reported earlier in the corpus striatum. This suggests that serotoninergic modulation of dopamine neurons is a generally-occurring phenomenon in the brain.     

Serotoninergic modulation of mesolimbic and frontal cortical dopamine neurons

Summary Potentiation of the effect of haloperidol on dopamine metabolism by the 5-HT uptake inhibitor CGP 6085 A, and antagonism of this effect by the 5-HT antagonist mianserin were observed in the mesolimbic area and the frontal cortex of the rat brain. A similar effect was reported earlier in the corpus striatum. This suggests that serotoninergic modulation of dopamine neurons is a generally-occurring phenomenon in the brain.     

Serotonin metabolism in the CNS in cerebellar ataxic mice

The metabolism of 5-hydroxytryptamine (5-HT) in the CNS was investigated in four kinds of morphologically different ataxic mice; reeler, staggerer, weaver and Purkinje cell degeneration mutants, and in hypocerebellar mice experimentally produced by injection of cytosine arabinoside. 5-HT and 5-hydroxyidoleacetic acid concentrations and tryptophan hydroxylase (TrpOH) activity were measured in the cerebrum, cerebellum and brain stem, respectively. TrpOH activity was significantly reduced only in the reeler mouse. The enhancements of the cerebellar 5-HT metabolism observed in the ataxic mice other than the reeler were supposed to be pseudo-enhancements subsequent to the cerebellar hypoplasia.     

Connection between 3H 5-HT and adenyl cyclase activation induced by 5-HT in preparations of cerebral glial membranes

Purified glial membrane preparations have been isolated from horse brain striatum. Tritiated 5-HT bound to these membranes with a high affinity (KD = 10 nM); the corresponding binding is reversible and appears specific of the serotoninergic structure. In parallel, 5-HT activates an adenylate cyclase with a low affinity (KD = 1 microM). The sites involved in this binding and in this adenylate cyclase activation appear different from the serotoninergic sites reported in the neuronal membrane preparations.     

Circadian rhythms of serotonin and the electrical activity of the frontal ganglion of the cockroach,Periplaneta americana

Summary Rhythmic circadian variations in the spontaneous electrical activity of the frontal ganglion (FG) of the cockroach,Periplaneta americana, have been shown, and the neurotransmitter (NT) involved in this activity has been identified as serotonin (5-hydroxytryptamine, 5-HT). During the 24-h day, the diurnal variations in the electrical activity and the levels of 5-HT and its immediate metabolite 5-hydroxyindole acetic acid (5-HIAA) were maximal at 24.00 h and minimal at 12.00 h.     

Changes in blood tryptophan level during sleep deprivation

Summary Prolonged sleep deprivation elicits a significant elevation of the plasma level of free tryptophan which appears to be involved in increased excretion of 5-HIAA during this state through enhanced 5-HT synthesis.     

Suppression of the immune response by drugs interfering with the metabolism of serotonin

The work was based on the assumption that neurohumoral control of the immune response, particularly in stressed animals, involves central serotoninergic mechanisms. Rats immunized with sheep erythrocytes were stressed by repeated restraints and/or treated with a precursor of serotonin (5-hydroxytryptophan, 5-HTP) or with an inhibitor of serotonin synthesis (parachlorophenylalanine, PCPA). As expected, repeated stresses reduced the plaque-forming cell (PFC) response. Treatment with 5-HTP also reduced the PFC response, and potentiated the immunosuppressive effect of stress. This was accompanied by increased metabolism of serotonin in the brain, as indicated by increased concentration of its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in cerebral tissue. Treatment with PCPA also suppressed the PFC response, but this suppression was accompanied by decreased levels of brain serotonin and of 5-HIAA. Plasma corticosterone levels were elevated in rats treated with PCPA. It seems that putative central effects of PCPA on serotoninergic regulation of the immune response were outweighed by its effects on corticosterone secretion and/or on lymphoid cells.     

Suppression of the immune response by drugs interfering with the metabolism of serotonin

Summary The work was based on the assumption that neurohumoral control of the immune response, particularly in stressed animals, involves central serotoninergic mechanisms. Rats immunized with sheep erythrocytes were stressed by repeated restraints and/or treated with a precursor of serotonin (5-hydroxytryptophan, 5-HTP) or with an inhibitor of serotonin synthesis (parachlorophenylalanine, PCPA). As expected, repeated stresses reduced the plaque-forming cell (PFC) response. Treatment with 5-HTP also reduced the PFC response, and potentiated the immunosuppressive effect of stress. This was accompanied by increased metabolism of serotonin in the brain, as indicated by increased concentration of its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in cerebral tissue. Treatment with PCPA also suppressed the PFC response, but this suppression was accompanied by decreased levels of brain serotonin and of 5-HIAA. Plasma corticosterone levels were elevated in rats treated with PCPA. It seems that putative central effects of PCPA on serotoninergic regulation of the immune response were outweighed by its effects on corticosterone secretion and/or on lymphoid cells.     

Hypertension mediated by the activation of the rat brain 5-hydroxytryptamine receptor sites

Summary 5-Hydroxytryptamine (5-HT) administered intraventricularly (i.vent.) in rats produced hypertension without considerable changes in heart rate. After transsection of the spinal cord or i.vent. administration of methysergide, 5-HT failed to produce the pressor effect. Thus, the hypertension results from the activation of 5-HT receptor sites of the rat brain.This work was supported by Union of Scientific Medical Institutions of Serbia (Grant No. 85).     

5-Hydroxytryptamine binding to butanol extracts from myelin fragments

Summary The myelin fraction of rat brain stem was treated with butanol-water mixtures, and the extracted proteolipids were separated by Sephadex LH₂₀ column chromatography. 2 peaks of proteolipids eluted in chloroform-methanol 4/1 showed the binding capacity for C¹⁴·5-HT. This finding suggests the necessity of the more careful investigations for the probability of proteolipids as receptor proteins in the central nervous system.     

In vivo measurement, by differential pulse voltammetry, of 5-HIAA in the striatum of the rat

Differential pulse voltammetry, performed with electrically treated carbon fiber electrodes, enables us to detect in vitro or in vivo in the striatum of anesthetized Rats, an oxidation peak 3 at a potential of +300 mV. Electrolytic, or 5,7-dihydroxytryptamine lesions of the medial forebrain bundle are followed by a decrease of respectively 59 and 62% of this peak. Biochemical measurements are significantly correlated to the measured peaks 3 and troughs. Thus, peak 3 increases obtained after injection of L-tryptophane and/or reserpine, as well as the troughs observed after injection of clorgyline and/or NSD 1015 confirm that the peak 3 is dependent upon 5-hydroxyindolacetic acid (5-HIAA) concentration.     

Cardioactive peptides of the CNS of the pulmonate snailLymnaea stagnalis

Summary In the pulmonate snailLymnaea stagnalis the cardioactive effects (tested on isolated auricles) of acetylcholine (ACh), 5-hydroxytryptamine (5-HT), the bivalve tetrapeptide FMRFamide, and of chromatographically separated snail brain substances have been established. Besides ACh and 5-HT, in brain extracts, small FMRFamide-like and large cardioexcitatory peptides were found.     

Injury-induced neurogenesis in the mammalian forebrain

It has been accepted that new neurons are added to the olfactory bulb and the hippocampal dentate gyrus throughout life in the healthy adult mammalian brain. Recent studies have clarified that brain insult raises the proliferation of neural stem cells/neural progenitor cells existing in the subventricular zone and the subgranular zone, which become sources of new neurons for the olfactory bulb and the dentate gyrus, respectively. Interestingly, convincing data has shown that brain insult invokes neurogenesis in various brain regions, such as the hippocampal cornu ammonis region, striatum, and cortex. These reports suggest that neural stem cells/neural progenitor cells, which can be activated by brain injury, might be broadly located in the adult brain or that new neurons may migrate widely from the neurogenic regions. This review focuses on brain insult-induced neurogenesis in the mammalian forebrain, especially in the neocortex.     

Depletion of angiotensin-converting enzyme 2 reduces brain serotonin and impairs the running-induced neurogenic response

Physical exercise induces cell proliferation in the adult hippocampus in rodents. Serotonin (5-HT) and angiotensin (Ang) II are important mediators of the pro-mitotic effect of physical activity. Here, we examine precursor cells in the adult brain of mice lacking angiotensin-converting enzyme (ACE) 2, and explore the effect of an acute running stimulus on neurogenesis. ACE2 metabolizes Ang II to Ang-(1–7) and is essential for the intestinal uptake of tryptophan (Trp), the 5-HT precursor. In ACE2-deficient mice, we observed a decrease in brain 5-HT levels and no increase in the number of BrdU-positive cells following exercise. Targeting the Ang II/AT1 axis by blocking the receptor, or experimentally increasing Trp/5-HT levels in the brain of ACE2-deficient mice, did not rescue the running-induced effect. Furthermore, mice lacking the Ang-(1–7) receptor, Mas, presented a normal neurogenic response to exercise. Our results identify ACE2 as a novel factor required for exercise-dependent modulation of adult neurogenesis and essential for 5-HT metabolism.     

Daily variation in the eye's 5-HT stores

Summary Eyes from mice have been assayed for 5-HT content at various times during the day. 5-HT levels are highest midway in the light period and lowest during the dark period. In general this daily variation conforms with other published reports for variation of 5-HT stores in brain and pineal.