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.     

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 vitro development ofXenopus skin glands producing 5-hydroxytryptamine and caerulein

The granular glands of amphibian skin synthesize and store a large amount of bioactive amines and peptides which are structurally similar to mammalian brain-gut peptides. To investigate the development of peptide- and amine-producing cells in the granular glands, pieces of dorsal skin taken at various stages fromXenopus laevis tadpoles were cultured, and the contents of caerulein and 5-hydroxytryptamine (5-HT) were measured. When pieces of skin from tadpoles at stages 57 to 60 (Nieuwkoop and Faber stages) were cultured in a medium containing 10% fetal calf serum (FCS medium) or one containing FCS treated with charcoal (chFCS medium), the caerulein and 5-HT levels were increased for the six days of the incubation period. The caerulein content was lower in the chFCS medium than in the FCS medium. Addition of thyroxine to the chFCS medium had no significant effect on the caerulein content. These results show that the caerulein-and 5-HT-producing cells of the granular glands can develop in a culture system with FCS- or chFCS-containing media, and suggest that FCS contains substances which are absorbed by charcoal and stimulate development of the amine- and peptideproducing cells of the glands. In a preliminary search for correlation between caerulein and 5-HT synthesis, addition of 5-hydroxytryptophan (5-HTP), a precursor to 5-HT, to the FCS medium increased 5-HT content and, conversely, caused significant decrease in caerulein content, suggesting that accumulation of caerulein in the granular glands is influenced by the amount of 5-HT synthesis. These studies indicate that this culture system is a useful model for investigating the development of peptide- and amine-producing cells.     

Coexistence of peptides with classical neurotransmitters

In the present article the fact is emphasized that neuropeptides often are located in the same neurons as classical transmitters such as acetylcholine, 5-hydroxy-tryptamine, catecholamines, gamma-aminobutyric acid (GABA) etc. This raises the possibility that neurons produce, store and release more than one messenger molecule. The exact functional role of such coexisting peptides is often difficult to evaluate, especially in the central nervous system. In the periphery some studies indicate apparently meaningful interactions of different types with the classical transmitter, but other types of actions including trophic effects have been observed. More recently it has been shown that some neurons contain more than one classical transmitter, e.g. 5-HT plus GABA, further underlining the view that transfer of information across synapses may be more complex than perhaps hitherto assumed.     

Effects of 18-hydroxydeoxycorticosterone on central nervous system excitability

The effects of 18-hydroxydeoxycorticosterone (18-OH-DOC) on central nervous system excitability were studied in adrenalectomized rats. Sixty-four evoked potentials (EP) recorded from the pontine reticular formation were averaged before and after the injection of vehicle and hormone. 750 micrograms of 18-OH-DOC dissolved in 0.5 ml of a 4:1 saline Cremophor-EL solution were injected i.v. A decrease of 55.7 +/- 6.1% in the amplitude of the EPs was observed with the hormone 16.3 min +/- 2.7 (SE) after injection. Amplitude values returned to baseline levels 38 min +/- 6.8 (SE) after injection. The secretion of 18-OH-DOC is greatly increased by ACTH and might modulate central nervous system function.     

Coexistence of peptides with classical neurotransmitters

Summary In the present article the fact is emphasized that neuropeptides often are located in the same neurons as classical transmitters such as acetylcholine, 5-hydroxy-tryptamine, catecholamines, -aminobutyric acid (GABA) etc. This raises the possibility that neurons produce, store and release more than the one messenger molecule. The exact functional role of such coesisting peptides is often difficult to evaluate, especially in the central nervous system. In the periphery some studies indicate apparently meaningful interactions of different types with the classical transmitter, but other types of actions including trophic effects have been observed. More recently it has been shown that some neurons contain more than one classical transmitter, e.g. 5-HT plus GABA, further underlining the view that transfer of information across synapses may be more compex than perhaps hitherto assumed.     

Selective effects of gonadal steroids on the response of peripheral serotonin receptors

The maximal contraction provoked by serotonin (5-HT) in isolated stomach strips of adult rats, a functional index for peripheral 5-HT receptors, was sexually differentiated, androgen-sensitive, and estrogen refractory. This is at variance with the reported sensitivity of central 5-HT receptors to estrogen.     

Selective effects of gonadal steroids on the response of peripheral serotonin receptors

Summary The maximal contraction provoked by serotonin (5-HT) in isolated stomach strips of adult rats, a functional index for peripheral 5-HT receptors, was sexually differentiated, androgen-sensitive, and estrogen refractory. This is at variance with the reported sensitivity of central 5-HT receptors to estrogen.     

Effects of 18-hydroxydeoxycorticosterone on central nervous system excitability

Summary The effects of 18-hydroxydeoxycorticosterone (18-OH-DOC) on central nervous system excitability were studied in adrenalectomized rats. Sixty-four evoked potentials (EP) recorded from the pontine reticular formation were averaged before and after the injection of vehicle and hormone. 750 g of 18-OH-DOC dissolved in 0.5 ml of a 41 saline Cremophor-EL solution were injected i.v. A decrease of 55.7±6.1% in the amplitude of the EPs was observed with the hormone 16.3 min±2.7 (SE) after injection. Amplitude values returned to baseline levels 38 min±6.8 (SE) after injection. The secretion of 18-OH-DOC is greatly increased by ACTH and might modulate central nervous system function.     

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

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.     

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.     

Oxidative stress and impaired oligodendrocyte precursor cell differentiation in neurological disorders

Cellular and Molecular Life Sciences - Oligodendrocyte precursor cells (OPCs) account for 5% of the resident parenchymal central nervous system glial cells. OPCs are not only a back-up for the loss...     

Exogenous melatonin accelerates re-entrainment: Attenuation of the circadian rhythm of metabolic rate in the canary,Serinus canaria

Administration of melatonin in the drinking water (200 g/ml in 1% ethanol) decreased the time of re-entrainment of the circadian rhythm of the metabolic rate (measured as oxygen uptake) of domestic canaries (Serinus canaria) after 10-h delay phase shifts of the light-dark (LD) cycle by 1.3 days on average. Associated with faster re-entrainment, the amplitude of the metabolic rhythm was attenuated by 46% on, average on the first day after the shift as compared with about 25% in the controls. After re-entrainment, the amplitude of the metabolic rhythm during melatonin administration was about 23% lower than in the controls. The minimum resting metabolic rate increased by ca 5% on average during treatment with melatonin. The results are consistent with the hypothesis that constant high plasma levels of melatonin act on higher levels of the circadian oscillatory system rather than by directly affecting peripheral or central photoreceptors.     

Glutamine synthetase activity in subdivisions of brain of the shark, Squalus acanthias

Specific activity of glutamine synthetase in Squalus acanthias (spiny dogfish) central nervous system regions was highest in the cerebellum and lowest in the spinal cord. The levels of activity may relate to the excitability of each region by regulating the glutamate pool.     

Distribution of type A and B monamine oxidase activities in the central nervous system of rat and chick.

The distribution of type A and B monamine oxidase (MAO) activities in the central nervous system (CNS) of rat and chick was investigated using 5-hydroxytryptamine and beta-phenylethylamine as specific substrates. The distribution of type A MAO was similar to that of type B MAO in rat CNS, but quite different in chick CNS. This may be ascribed to the difference in animal species. The major part of MAO activity in the spinal cord was found to be type A.     

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.     

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.     

Lactate dehydrogenase and glutamate dehydrogenase activities in the circumventricular organs of rat brain following neonatal monosodium glutamate

Glutamate (glu) an excitatory neurotransmitter amino acid, is present in high concentrations in the mammalian central nervous system and is the most abundant amino acid in our daily diet. In the present study the activities of lactate dehydrogenase (LDH) and glutamate dehydrogenase (GDH) were evaluated in the circumventricular organs (CVO) of the brain in 25-day-old rats following MSG administration at a dose of 4 mg/g b.wt during the first ten days of life. The results show the LDH activity increased to 265% of that in the control (p<0.001), whereas GDH activity was significantly decreased (p<0.05), The great elevation in LDH, a cytoplasmic marker enzyme, is apparently due to cytoskeletal changes brought about as a consequence of glu toxicity, whereas lowered GDH activity indicates altered glu homostasis in the blood-brain-barrier deficient areas following neonatal exposure to glu.     

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.     

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.