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.     

Fluorescence microscopical study of 5-hydroxytryptamine storage organelles in mepacrine-incubated blood platelets of beige mice (Chediak-Higashi syndrome)

Summary The number and fluorescence intensity of fluorescent granules (5-HT storage organelles) of mepacrine-incubated blood platelets of beige mice (Chediak-Higashi syndrome) are decreased compared to those of control mice platelets. This indicates both quantitative and qualitative changes of the 5-HT organelles, namely a reduced number and a reduced storage capacity, respectively.     

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.     

The occurrence of 5-hydroxytryptamine in the holothurian,Pentacter crassa

Summary 5-Hydroxytryptamine (5-HT) and hypoxanthine were isolated chromatographically from the holothurianPentacter crassa. This study was initiated as a result of the observed hypotensive activity of aP. crassa extract. This activity was also encountered in extracts of the holothuriansThelenota ananus andStichopus chloronatus and can be attributed to 5-HT.     

Respective effects on locomotor activity of injections of 5, 7-DHT in median raphe nucleus and of 6-OHDA in the mesolimbic dopaminergic group area in the rat]

This experiment was performed in order to demonstrate that the locomotor hyperactivity provoked by a radiofrequency lesion of the ventral mesencephalic tegmentum-A10 DA group area was not due to a 5-HT fiber damage. Four groups of Rats were used. First groups II and IV received a 5, 7-DHT injection in the median raphe; groups I and III received the vehicle. Locomotor activity was measured in a circular corridor 10 and 30 days; no hyperactivity was obtained. Then the same groups received a 6-OHDA injection, bilaterally in the A 10 area (groups III and IV) or the vehicle (groups I and II); the activity was measured 10 days later: significant hyperactivity was obtained with groups III and IV, without statistical differences between these two groups. In conclusion (i) 5-HT neurons are not directly involved in the VMT-hyperactivity, (ii) the DA A 10 neurons seem to be a critical anatomical target for this symptom.     

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.     

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.     

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.     

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.     

Regional distribution of lactate dehydrogenase isoenzymes in adult rat brain.

The highest lactate dehydrogenase (LDH) activity was found in thalamus, statistically significantly less in cerebral and cerebellar cortex and the lowest in pons. LDH1 and LDH4+5 represented 58% and 23% of the total activity in cerebral cortex, 54% and 20% in thalamus, 42% and 4% in cerebellar cortex and 55% and 7% in pons, respectively.     

Extraneuronal serotonin accumulation in peripheral arteries of the rat

Accumulations of serotonin (5-HT) and norepinephrine (NE) were compared in control and 6-hydroxydopamine (6-OHDA) pretreated rat aorta, mesenteric and tail arteries. The distribution of these amines was corrected by subtracting tissue uptake of tritiated sorbitol in the extracellular space. 5-HT greatly accumulated both in control and 6-OHDA pretreated arteries. In contrast, NE accumulation in mesenteric and tail arteries was substantially decreased after 6-OHDA treatment. In the aorta 6-OHDA pretreatment did not affect the accumulation of both amines. These findings suggest that 5-HT accumulation in these arteries is mainly extraneuronal, and NE mainly neuronal. Since the accumulation of 5-HT in the aorta was not influenced by pretreatment with 10 microM NE, the extraneuronal uptake mechanisms for 5-HT and NE appear to be different.     

Comparison of diurnal and nocturnal rates of 5-hydroxytryptamine turnover in the rat mediobasal hypothalamus

Rates of 5-hydroxytryptamine (5-HT) turnover in the mediobasal hypothalamus of male rats were estimated using pharmacological methods during the daytime and at night. Concentrations of 5-HT in this hypothalamic area were higher nocturnally than diurnally; this was apparently due to increased 5-HT synthesis and decreased 5-HT catabolism at night.     

Comparison of diurnal and nocturnal rates of 5-hydroxytryptamine turnover in the rat mediobasal hypothalamus

Summary Rates of 5-hydroxytryptamine (5-HT) turnover in the mediobasal hypothalamus of male rats were estimated using pharmacological methods during the daytime and at night. Concentrations of 5-HT in this hypothalamic area were higher nocturnally than diurnally; this was apparently due to increased 5-HT synthesis and decreased 5-HT catabolism at night.Supported by NIH grant RR07187 (TSK) and NIH grant HD10202 (Neuroendocrine Core).     

The enteric neural receptor for 5-hydroxytryptamine

An enteric neural receptor for serotonin (5-HT) has been characterized. This receptor was assayed, using 3H-5-HT as a radioligand, by rapid filtration of isolated enteric membranes and by radioautography. In addition, intracellular recordings were made from ganglion cells of the myenteric plexus. High affinity, saturable, reversible, and specific binding of 3H-5-HT was demonstrated both to membranes of the dissected longitudinal muscle with adherent myenteric plexus and the mucosa-submucosa. Radioautographs showed these 3H-5-HT binding sites to be in myenteric ganglia and in a broad unresolved band at the mucosal-submucosal interface. Antagonists active at receptors for other neurotransmitters than 5-HT, at either of the two known types of CNS 5-HT receptor, and at 5-HT uptake sites on serotonergic neurons failed to inhibit binding of 3H-5-HT. The structural requirements of analogues for binding to the enteric 5-HT receptor matched the known pharmacology of M or neural 5-HT receptors. A novel 5-HT antagonist was found. This compound, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (5-HTP-DP), antagonized the action of 5-HT on type II/AH cells of the myenteric plexus but did not affect the release or actions of acetylcholine (nicotinic or muscarinic) or substance P. 5-HTP-DP was also an equally potent displacer of 3H-5-HT from its binding sites on enteric membranes. It is concluded that the sites responsible for specific binding of 3H-5-HT are enteric M or neural 5-HT receptors. These receptors differ from those now known to be present in the CNS.     

The enteric neural receptor for 5-hydroxytryptamine

Summary An enteric neural receptor for serotonin (5-HT) has been characterized. This receptor was assayed, using³H-5-HT as a radiologand, by rapid filtration of isolated enteric membranes and by radioautography. In addition, intracellular recordings were made from ganglion cells of the myenteric plexus. High affinity, saturable, reversible, and specific binding of³H-5-HT was demonstrated both to membranes of the dissected longitudinal muscle with adherent myenteric plexus and the mucosa-submucosa. Radioautographs showed these³H-5-HT binding sites to be in myenteric ganglia and in a broad unresolved band at the mucosal-submucosal interface. Antagonists active at receptors for other neurotransmitters than 5-HT, at either of the two known types of CNS 5-HT receptor, and at 5-HT uptake sites on serotonergic neurons failed to inhibit binding of³H-5-HT. The structural requirements of analogues for binding to the enteric 5-HT receptor matched the known pharmacology of M or neural 5-HT receptors. A novel 5-HT antagonist was found. This compound, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (5-HTP-DP), antagonized the action of 5-HT on type II/AH cells of the myenteric plexus but did not affect the release or actions of acetylcholine (nicotinic or muscarinic) or substance P. 5-HTP-DP was also an equally potent displacer of³H-5-HT from its binding sites on enteric membranes. It is concluded that the sites responsible for specific binding of³H-5-HT are enteric M or neural 5-HT receptors. These receptors differ from those now known to be present in the CNS.     

A circannual rhythm in bovine pineal serotonin

Summary Bovine pineal serotonin (5-HT) was analyzed at the time of the solstices and equinoxes from December, 1975 until June, 1978. The highest values of 5-HT were detected at the winter solstices and lowest values at the summer solstices of each year examined. The peaks in bovine pineal 5-HT correspond with a lessened fertility in cattle reported during the winter months.Supported by NSF grant PCM 77-05734.The authors wish to thank Roeglein's Provision Company, Beef Processing Division and especially H. Schmidt, Foreman.     

Tetanus intoxication causes an increment of serotonin in the central nervous system

Summary Mice injected with tetanus toxin (TTx) showed an increase of 5-hydroxytryptamine (serotonin, 5-HT) levels in the central nervous system. The increment was not uniform thoughout the central nervous system. Particularly significant were the 25% and 80% increases observed, respectively, in whole brain and spinal cord. The levels of dopamine and norepinephrine remained unchanged. The subsequent studies of 5-HT turnover revealed a synthesis rate in the tetanic animals that was almost double that of controls. The degradation rate of the amine as well as the levels of 5-hydroxyindolacetic acid were unaffected.     

Tetanus intoxication causes an increment of serotonin in the central nervous system

Mice injected with tetanus toxin (TTx) showed an increase of 5-hydroxytryptamine (serotonin, 5-HT) levels in the central nervous system. The increment was not uniform throughout the central nervous system. Particularly significant were the 25% and 80% increases observed, respectively, in whole brain and spinal cord. The levels of dopamine and norepinephrine remained unchanged. The subsequent studies of 5-HT turnover revealed a synthesis rate in the tetanic animals that was almost double that of controls. The degradation rate of the amine as well as the levels of 5-hydroxyindolacetic acid were unaffected.     

The loss of biological activity of 5-hydroxytryptamine creatinine sulphate.

5-Hydroxytryptamine creatinine sulphate loses its biological activity when maintained at room temperature. The loss of 5-HT activity (in stimulating sodium transport across frog skin) is greater than the loss of creatinine sulphate activity (inhibition of sodium transport).     

The loss of biological activity of 5-hydroxytryptamine creatinine sulphate

Summary 5-Hydroxytryptamine creatinine sulphate loses its biological activity when maintained at room temperature. The loss of 5-HT activity (in stimulating sodium transport across frog skin) is greater than the loss of creatinine sulphate activity (inhibition of sodium transport).