Amount Of Serotonin Research Articles

The effect of intra-amygdalar leptin administration on anxiety, depression and learning behaviors in rats

Leptin is released by adipose tissue. Leptin can cross the blood–brain barrier and bind to receptors on neurons in brain areas to exert its biological function when released into circulation. This study aimed to determine the influences of intra-amygdalar administration of high and low doses of leptin on anxiety, depression, learning behaviors of rats. In the experimental protocol I, intra-amygdalar injection of high and low doses of leptin (0.1 and 1 μg/ kg) and saline were administered 30 min before the behavioral tests. Then, the animals were exposed to open field, elevated plus maze, Porsolt and Morris water maze tests for measuring of behaviors. In experimental protocol 2, the cerebrospinal fluids of all groups of experimental protocol 1 were collected by microdialysis method and then were analyzed by HPLC. The effect of the low dose of leptin was significant on the open field. The effect of the high and low dose of leptin was significant on the elevated plus maze test. The effect of the low dose of leptin was significant on mobility in the center of the Porsolt. A high dose of leptin group had spent less time around the platform than controls in the Morris water maze test. HPLC analysis showed that the amount of serotonin and glutamate in the amygdala region increased after low dose leptin administration. Intra-amygdalar injection of low doses of leptin may decrease anxiety and depression-like behavior in rats by increasing serotonin and glutamate levels in the amygdala.

Membrane serotonin transporter as a Biomarker of Pulmonary arterial hypertension in children with Congenital Heart Defect

18 young children (aged from 1 month old to 2 years old) with congenital heart disease were observed. During observation they were divided into 2 groups. Group I-8 children with CHD, not complicated by PAH. Group II 11 children with CHD, complicated by PAH. The content of serotonin and its transporter in platelets, the amount of serotonin in serum were determined. Serotonin content was determined by enzyme-linked immunosorbent assay. The study was performed using the Serotonin ELISA diagnostic kit, IBL Hamburg on the Evolis automated robotic station (BioRad). To determine the Sodium-Dependent serotonin transporter (SLC6A4) there was used the method of quantitative sandwich ELISA of Cusabio production. The main initiator of the development of PAH is development of endothelial dysfunction of the pulmonary vessels. Since the cause of this dysfunction is associated with functional disorders of the serotonergic system, our task was to determine the content of SERT and serotonin in platelets in the studied groups. We suggest that the serotonin transporter (SERT), which is responsible for the proliferation of the pulmonary artery smooth-muscle cells (PASMC), can be used as a biomarker for predicting and diagnosing PAH in children with CHD. The need for early biomarkers in the diagnosis of PAH in children is claimed by scientists from many countries of the world [1, 2]. The results of our studies showed a significant increase in the concentration of SERT in platelets in group II, compared with group I more than several times. The serotonin content in platelets in children of group II tended to decrease as compared with group I. Perhaps, an excessive increase in transporters in platelets is sufficient in itself for the induction of PASMC hyperplasia and the subsequent development of PAH. It is necessary to continue research in this direction, which will help to reveal and understand the molecular mechanisms by which SERT regulates the proliferation of PASMC and the role of serotonin and its transporter in the development of PAH in children.

SELF HARM BEHAVOIR

In this study, it is aimed to examine this research from a wide perspective and to emphasize the importance of more specific studies on the subject.
 In this research, national and international studies on self-harm behavior were compiled.
 Self-injurious behavior is frequently encountered as an advanced behavioral problem. (Şipal, 2010) Self-injurious behavior is that a person can harm one's own tissues in such a way as to cause severe acts without the will to die consciously. Self-injurious behavior is associated with many psychiatric disorders. In addition, deliberate self-harm behavior should be separated from suicide attempts. Self-injurious behavior usually begins in adolescence. “In the community sample studies, it was found that self-injurious behavior was seen in 1/3 and 1/2 of adolescents (Lloyd-Richardson et al. 2007, Yates et al. 2008). self-injurious behavior typically begins in adolescence and often occurs impulsively; adolescents and young adulthood (Claassen et al. 2006) (Bildik, Somer, Basay, Basay, &Ozbaran, 2012). According to the results of the study, identity confusion and low self-esteem symptoms were found to be significantly more frequent in adolescents with self-injurious behavior (Akdemir, Zeki, Unal, Kara, & Cetin, 2013). It is observed that traumas experienced in the past are related to deliberate self-harm behavior. There are many reasons for self-harm behavior. One of them is abuse. If the trauma experienced is remembered, self-harm behavior arises in order to replace the high level of anxiety with physical pain. Miller and Favazza investigated the reasons for self-mutilation and listed the factors that caused self-mutilation as follows: To have a sense of relaxation; Suppressing emotional pain; Moving away from the feeling of emptiness to show their experiences.(Aksoy, Ögel, 2003). However, in individuals who frequently repeat the act of self-harm, feelings of embarrassment, guilt, regret, and desire for social isolation may also be exacerbated by the stimulation of other negative emotions. (Gratz, 2003) It has been suggested that there may be many biological factors under self-harm behavior. Some of them are opiate system disorder, hypersensitivity of dopamine receptors, decrease in the amount of serotonin. There are psychodynamic opinions about self-harm behavior. Emerson (1913) and Fenichel (1945) stated that self-harm behavior is a substitute for masturbation and is equivalent. Then, behaviorists related to self-harm behavior started to study. According to the behavioral approach, self-harm behavior was later learned and considered as a sense of self-protection against the difficulties of life.
 Intentional self-harm behavior is difficult to explain, but in recent years it has attracted attention by researchers (Chapman, Gratz, & Brown, 2006). In line with the literature review on the subject, it is seen that the studies on this subject need to be more detailed and more specialized case groups should be examined.

ШЛЯХ БІОСИНТЕЗУ СЕРОТОНІНУ В ГОЛОВНОМУ МОЗКУ ЩУРІВ ЗА УМОВ ЕКСПЕРИМЕНТАЛЬНОГО ОЖИРІННЯ, ВИКЛИКАНОГО ДОВГОТРИВАЛИМ УВЕДЕННЯМ ПРОГЕСТЕРОНУ

Obesity is one of the most common complex health problem. The pathway of serotonin synthesis takes part in neuroendocrine regulation, as well as in the regulation of a number of behavioral functions of the body and fat deposition. Serotonin is a mediator of the amine nature, which functions as a neurotransmitter and tissue hormone. The greatest amount of serotonin is synthesized in the brain and 12 duodenum. As a neurotransmitter, serotonin affects both directly and indirectly on the function of most brain cells. Female hormone progesterone influence on serotonin functions. One of the effect of progesterone is increasing of amount of fat tissue during the pregnancy. Long-term using of progesterone in hormone substitution therapy or as part of contraception also lead to fat accumulation effect. The levels of activity of serotonergic system enzymes, tryptophan hydroxylase, tryptophan decarboxylase and monoamine oxidase (MAO), and tryptophan, 5-hydroxytryptophan, serotonin and 5-hydroxyindoleacetic acid concentrations in the rat brain under obesity conditions caused by prolonged administration of progesterone were determined in this study. Studies have shown that the content of tryptophan, 5-hydroxytryptophan, serotonin and 5-hydroxyindoleacetic acid in the brain of rats under obesity caused by prolonged administration of progesterone increased in comparison with the rats of the control group. The levels of tryptophan hydroxylase and MAO activity decreased, and tryptophan decarboxylase activity levels increased in the rat brain under obesity conditions caused by prolonged administration of progesterone. Thus, as a result of our studies, we found an imbalance in the system of serotonin metabolism in the brain of rats with the development of hormonal obesity induced by prolonged administration of progesterone, which may indicate the involvement of the serotonergic neurotransmitter system in the mechanisms of the development of obesity and concomitant diseases.

Evidences for amelioration of reserpine-induced fibromyalgia in rat by low dose of gamma irradiation and duloxetine

Objective: Fibromyalgia is a prevalent disorder characterized by chronic widespread pain and complex symptoms. This study was conducted to investigate the potential therapeutic effect of low-dose irradiation (LDI) alone or in combination with duloxetine on the reserpine-induced fibromyalgia in rats.Methods: Fibromyalgia was induced by administration of reserpine (1 mg/kg/s.c) for 3 consecutive days. Duloxetine (30 mg/kg, p.o) was administered 60 min before a forced swimming test (FST), and rats were exposed to a single dose of γ-radiation (0.5 Gy) 1 day before the FST.Results: Reserpine significantly increased immobility time in the FST, decreased the amount of 5-hydroxytryptamine, dopamine, and norepinephrine in cerebral cortex. It also increased malondialdehyde and nitric oxide and reduced glutathione contents in brain tissue. LDI alone or combined with duloxetine completely antagonized reserpine-induced fibromyalgia as assessed by the measured parameters. One of the most significant findings in this study was that the therapeutic effect of duloxetine was more pronounced by its combination with LDI. A possible mechanism of action of LDI and duloxetine responsible for their therapeutic effect was discussed.Conclusion: On the basis of the presented evidences, it could be concluded that LDI alone or combined with duloxetine could be of value in the management of fibromyalgia.

Kinetics of extracted bioactive components from mushrooms in artificial digestive juices

ABSTRACTThis article presents a study on fruiting bodies of Boletus badius, Boletus edulis, Cantharellus cibarius, Lactarius deliciosus, Leccinum scabrum, Suillus bovinus, Suillus luteus, Pleurotus ostreatus, Tricholoma equestre, Armillaria mellea, Agaricus bisporus, and Auricularia polytricha. The amounts of their health-promoting bioelements and physiologically significant indole and phenolic compounds were determined. The significance of edible mushrooms in the human diet and in disease prevention were also established. The high-performance liquid chromatography was used to assess the contents of indole compounds and phenolic acids. The atomic absorption spectroscopy was applied to determine bioelements. In all samples, the content of 5-hydroxy-L-tryptophan was studied. The highest extraction amount of serotonin was found for P. ostreatus species. Phenolic compounds were determined in the conditions described in the present study for the first time. Additionally, protocatechuic, p-hydroxybenzoic, syringic, and gallic acids were determined.

Rootstock effect on serotonin and nutritional quality of tomatoes produced under low temperature and light conditions

In this study, we explored the capacity of different tomato rootstocks to improve the nutritional value of tomatoes grown in a greenhouse during the winter–spring period under low temperature and light conditions. The results showed that relative to nongrafted plants, some grafted rootstocks either did not affect or had detrimental effects on the nutritional parameters measured. In addition, the amount of serotonin was significantly lower in tomatoes from all grafted rootstocks than in tomatoes from the nongrafted plants. Nevertheless, relative to the nongrafted plants, some grafted treatments increased total macroelements (by 1.16 times), total microelements (by 1.43 times), protein content (by 17%), free total and essential amino acids (by respectively 23% and 19%), total phenolic compounds (by 11%), vitamin C (by 13.8%), lycopene (by 48%), and also total hydrocinnamic acids (by 67%) and flavonoids (by 279%). As the grafted treatments did not increase the tomato yield, we hypothesize that these compounds accumulated in the tomatoes due to the lack of increased biomass, which prevented a dilution effect on the compounds of interest in the fruits.

The Impact of Chronic Social Stress on Emotional Behavior in Mice and the Therapeutic Effect of Peripheral Mild-Heat Stimulation

In today’s stressful society, mental diseases such as adjustment disorder, affective disorders including anxiety and depression, and chronic fatigue syndrome could be attributed to social stress and are considered as serious social problems. It has been long known in the acupuncture and moxibustion therapies in Japan and China that stimulation at Zhongwan and Taichong points have effects on stress-related anxiety and depression. In the present study, we therefore tested the effect of peripheral mild-heat stimulation at Zhongwan and Taichong on anxiety and brain biochemistry using a mouse model of chronic social stress. Male ddY mice (4 weeks old) were stressed by isolated rearing for 6 weeks. They received mild-heat stimulation (43℃ for 5 min) at Zhongwan and Taichong under isoflurane anesthesia after 4 weeks of the social isolation 3 times a week for 2 weeks, using the “Stress Free Apparatus” (Ryoken Co., Ltd). Control mice received only isoflurane anesthesia. Group-reared mice also underwent the same stimulus/anesthesia sessions. Two days after the last peripheral heat stimulation, anxiety was determined by the light/dark box test as the time spent in the light compartment and the number of transfer between the light and dark compartments. Before and after the last stimulation, blood was collected from an artery at the back of the eye, and serum corticosterone, immunoglobulin E (IgE) which was an index of the inflammatory immune system, and interleukin 6 (IL-6) were measured using ELISA Kit. The frontal cortex was collected after the behavioral test, and the dopamine and serotonin contents were measured also by ELISA Kit. A significant decrease of the time spent in the light compartment was observed after the isolated rearing (p < 0.01). Mild-heat stimulation significantly increased the time spent in the light compartment, indicating an anti-anxiety effect. Serum corticosterone, IgE and IL-6 were increased after stress, and the amount of serotonin in the frontal cortex was found decreased. The increased corticosterone, IgE and IL-6 were cancelled by mild-heat stimulation. These results suggest that chronic social isolation has negative biological and emotional impacts in mice and that peripheral mild-heat stimulation alleviates at least part of these stress effects.

Serotonergic mechanism of the relieving effect of bee venom acupuncture on oxaliplatin-induced neuropathic cold allodynia in rats.

BackgroundOxaliplatin, an important chemotherapy drug for advanced colorectal cancer, often induces peripheral neuropathy, especially cold allodynia. Our previous study showed that bee venom acupuncture (BVA), which has been traditionally used in Korea to treat various pain symptoms, potently relieves oxaliplatin-induced cold allodynia in rats. However, the mechanism for this anti-allodynic effect of BVA remains poorly understood. We investigated whether and how the central serotonergic system, a well-known pathway for acupuncture analgesia, mediates the relieving effect of BVA on cold allodynia in oxaliplatin-injected rats.MethodsThe behavioral signs of cold allodynia in Sprague–Dawley (SD) rats were induced by a single injection of oxaliplatin (6 mg/kg, i.p.). Before and after BVA treatment, the cold allodynia signs were evaluated by immersing the rat’s tail into cold water (4°C) and measuring the withdrawal latency. For BVA treatment, a diluted BV (0.25 mg/kg) was subcutaneously administered into Yaoyangguan (GV3) acupoint, which is located between the spinous processes of the fourth and the fifth lumbar vertebra. Serotonin was depleted by a daily injection of DL-p-chlorophenylalanine (PCPA, 150 mg/kg, i.p.) for 3 days. The amount of serotonin in the spinal cord was measured by ELISA. Serotonergic receptor antagonists were administered intraperitoneally or intrathecally before BVA treatment.ResultsThe serotonin levels in the spinal cord were significantly increased by BVA treatment and such increase was significantly reduced by PCPA. This PCPA pretreatment abolished the relieving effect of BVA on oxaliplatin-induced cold allodynia. Either of methysergide (mixed 5-HT1/5-HT2 receptor antagonist, 1 mg/kg, i.p.) or MDL-72222 (5-HT3 receptor antagonist, 1 mg/kg, i.p) blocked the anti-allodynic effect of BVA. Further, an intrathecal injection of MDL-72222 (12 μg) completely blocked the BVA-induced anti-allodynic action, whereas NAN-190 (5-HT1A receptor antagonist, 15 μg, i.t.) or ketanserin (5-HT2A receptor antagonist, 30 μg, i.t.) did not.ConclusionsThese results suggest that BVA treatment alleviates oxaliplatin-induced acute cold allodynia in rats via activation of the serotonergic system, especially spinal 5-HT3 receptors. Thus, our findings may provide a clinically useful evidence for the application of BVA as an alternative therapeutic option for the management of peripheral neuropathy, a dose-limiting side effect that occurs after an administration of oxaliplatin.

Diabetic peripheral neuropathy therapy-induced activation of humoral serotonin and endogenous neurotrophins

The indicators of pain and psychological status, the concentrations of serum serotonin and blood platelets, and the levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor were studied in 82 patients with diabetic peripheral neuropathy (DPN). Along with conventional treatment aimed to normalize carbohydrate metabolism, 30 patients with DPN received actovegin in an intravenous, jetwise dose of 10.0 ml for 10 days. Prior to treatment, their pain intensity was 5.94±1.2 and 29.6±6.24 scores according to a visual analogue scale (VAS) and PainDETECT, respectively. The subclinical level of anxiety and depression was noted. The amount of serotonin in the serum (90.39±55.43 ng/ml) and blood platelets (298.13±80.33 ng/ml) was lower than that in the control. The content of serum BDNF in DPN was also substantially lower (419.27±132.7 pg/ml; p<0.04) than that in the control. After treatment, the actovegin group showed a more significant reduction in pain syndrome according to the VAS (3.5±0.6 cm; p=0.005) and PainDETECT (19.4±4.1 scores, p=0.005), a decrease in the degree of anxiety and depression according to the Beck inventory (11.4±1.4 scores; p=0.001), and an increase in BDNF levels up to 979.71±289.9 pg/ml. Serum serotonin and blood platelets increased up to 206.13±78.3 and 477.06±114.45 ng/ml, respectively; which is indicative of the correct choice of the treatment for DPN.

Biological Clocks in the Duodenum and the Diurnal Regulation of Duodenal and Plasma Serotonin

Serotonin in blood plasma is primarily synthesized in the duodenum, as brain derived serotonin does not cross the blood-brain barrier. Because serotonin in the brain and retina is synthesized under the control of a circadian clock, we sought to determine if a circadian clock in the duodenum regulates serotonin synthesis and release in blood. We examined gene expression in the duodenum of chickens at different times of the day and found that the duodenum rhythmically expresses molecular circadian clock genes and genes controlling serotonin biosynthesis, specifically tryptophan hydroxylase, in a light dark cycle (LD). Analysis of the duodenum and blood plasma showed that the amount of serotonin in the duodenum varies across the day and that serotonin profiles in blood plasma are also rhythmic in LD, but were not rhythmic in constant darkness. Because serotonin in the gut affects duodenal nutrient absorption and gut motility, the control of serotonin production in the duodenum by LD cycles could provide an additional mechanism by which the external environment controls nutrient uptake and digestive function. The diurnal regulation of plasma serotonin may also serve as an additional biochemical signal in the blood encoding time and could be used by target tissues to indicate the status of nutrient absorption.

Study of the absorptive intestinal function in an experimental model of chronic alcohol intoxication

Aim. To study the absorptive function of the rat intestine on the background of prolonged alcohol intoxication. Methods. The study was performed on 24 nonlinear white male rats (12 animals in the control and experimental groups) weighing 220-240 g, which had a daily consumption of 20° ethanol solution (ethyl alcohol) for the duration of 180 days. After 6 months perfusion of the isolated segment of jejunum with a dextrose (glucose) solution 35 mmol/L was performed by in the rats the method A.M. Ugolev. The luminescence-histochemical method was used to examine the content of catecholamines and serotonin in the neuroamine containing structures. Results. In the control rats, the rate of absorption in the first 10 min of perfusion reached a maximum value with a further decrease in the intensity of absorption. The content of serotonin and catecholamines in the absorptive epithelial layer of the jejunal villi was lower than in the muscle membrane. In the experimental rats the content of biogenic amines in the wall of the jejunum increased: the amount of serotonin in the absorptive layer of the villi increased up to 122% and in the muscle membrane - up to 126%. The content of catecholamines also increased up to 154% in the muscle membrane and up to 124% in the epithelial layer in the area of the villi compared with controls. In conditions of chronic alcohol intoxication the rate of absorption of dextrose (glucose) during perfusion in the first 30 minutes was reduced by 33% compared with the control. During the next hour, the intensity of absorption reduced by 45% (55% of control). After 1.5 hours the absorption increased slightly, accounting for 64% of the control value and by the end of the 2nd hour the intensity of the absorption reached 91%. Conclusion. An increase in content of catecholamines and serotonin in the mucous and muscular layers of the intestine in chronic alcohol intake and a decrease in the intensity of the absorption of dextrose (glucose) was established; in the setting if modified combined effects of neurotransmitters on smooth muscle cells an increased motor effect is formed, which is accompanied by rapid evacuation of the intestinal chyme with a reduction in the rate of absorption

Postural-motor reactions and the distribution of brain monoamines in rats of a catatonic strain at early developmental stages

Motor responses were studied in neonatal rats of the GC strain, which is characterized by hereditary catatonia. These pups differed from control Wistar pups in having a greater proportion of dyskinetic movements and postures on days 1–2 of neonatal development and a lower number of motor actions in later development. GC pups had elevated noradrenaline levels in the hemispheres on the 7th, 10th, and 14th days in comparison to Wistar rats and in the brainstem on day 10. In GC pups, the amount of serotonin in the hemispheres on days 1 and 14 and in the brainstem on day 14 was lower than in Wistar rats. The level of 5-hydroxyindoleacetic acid in GC pups was lower than in Wistar on days 1 and 7. We compared the characteristics of transmitter mechanisms on the basis of various models: GC rats, pharmacological in vivo models, and spinal in vitro preparations from animals at early developmental stages.

DISTINCT ROLES for Rap1b In PLATELET SECRETION and INTEGRIN aIIBb3 OUTSIDE-In SIGNALING

Abstract 2200Rap1b is activated by platelet agonists, and plays a critical role in integrin aIIbb3 inside-out signaling and platelet aggregation. In this study, we identify two novel functions of Rap1b in platelets. We show that agonist-induced Rap1b activation plays an important role in stimulating secretion of platelet granules. We also show that aIIbb3 outside-in signaling can activate Rap1b, and integrin outside-in signaling-mediated Rap1b activation is important in facilitating platelet spreading on fibrinogen and clot retraction. Rap1b deficient platelets had diminished ATP secretion and P-selectin expression induced by thrombin or collagen. Defect in secretion of Rap1b deficient platelets was not due to reduced granule contents, because the amount of serotonin (5HT) and platelet factor 4 (PF4) in Rap1b deficient platelets is similar to that in wild type platelets. Data from transmission electron microscopy indicate that under resting conditions, wild type and Rap1b deficient platelets had normal discoid shapes with similar numbers of granules. When stimulated with thrombin, wild type platelets showed an irregular appearance with protruding filopodia and lack of granules. In contrast, thrombin-stimulated Rap1b−/– platelets showed that more Rap1b−/– platelets contained visible a granules than wild type platelets. Dense granules were also more obvious in thrombin-stimulated Rap1b−/– platelets than wild type platelets. Importantly, addition of low doses of ADP and/or fibrinogen restored aggregation of Rap1b deficient platelets. Furthermore, we found that Rap1b was activated by platelet spreading on immobilized fibrinogen, a process that was not affected by P2Y12 or TP deficiency, but was inhibited by the selective Src inhibitor PP2, the PKC inhibitor Ro-31-8220, or the calcium chelator demethyl-BAPTA. Clot retraction was abolished, and platelet spreading on fibrinogen was diminished in Rap1b deficient platelets compared with wild type controls. The defects in clot retraction and spreading on fibrinogen of Rap1b deficient platelets were not rescued by addition of MnCl2, which elicits aIIbb3 outside-in signaling in the absence of inside-out signaling. Thus, our results reveal two different activation mechanisms of Rap1b as well as novel functions of Rap1b in platelet secretion and in integrin aIIbb3 outside-in signaling. Disclosures:No relevant conflicts of interest to declare.

Decreased hormone content of immune cells in children during acute lymphocytic leukemia (ALL) — Effect of treatment

Histamine, serotonin and triiodothyronine (T3) content of different circulating lymphocyte subsets of leukemic (acute lymphocytic leukemia, ALL) and non-leukemic (control) children were investigated by multicolor flow cytometry. The hormone contents of the cells were followed from the time of diagnosis till the end of treatment. Each hormone could be detected in every time in the investigated cell types, although the amounts of them changed during the treatment.T lymphocytes: Significantly lower amount of serotonin was found in each T cell subsets (Th, Tc and activated T lymphocytes) of leukemic children compared to the healthy control group at the time of diagnosis and it was permanently low during the maintenance therapy. The decreased amount of serotonin could be demonstrated in Tc and Th cells even at one year after the end of treatment. However, there was no alteration in the histamine and T3 content of T cell subsets in the time of diagnosis, but significant decrease was detected during the maintenance therapy and after treatment.NK cells: The serotonin and T3 contents of NK cells (both NK and NKT subsets) were significantly lower at the time of diagnosis and during the maintenance therapy. Similar decrease was detected in the case of serotonin in B cells. Although there was no difference in the T3 content of B cells at the time of diagnosis, significantly lower amounts could be detected during the therapy compared to the healthy control group. The serotonin concentration remained low for years after the end of treatment, both in B and NK cells. These observations might have diagnostic and prognostic importance.

Correlation between increased urinary serotonin levels and coronary artery disease in cigarette smoking patients

Platelets secrete serotonin (5-hydroxytryptamine), which has several effects on the vascular wall and promotes thrombogenesis, mitogenesis, and the proliferation of smooth muscle cells. We therefore measured excreted levels of 5-hydroxytryptamine (5-HT) concentrations in urine as a means of assessing vascular lesions in patients with coronary artery disease ( CAD). Materials and methods: Subjects who underwent coronary angiography were classified into 2 groups according to their diagnosis. The CAD group consisted of 33 patients with coronary artery stenosis, whereas the healthy control group consisted of 30 subjects. An isocratic high-performance liquid chromatographic (HPLC) system with an electrochemical detector was used for the HPLC analysis of serotonin in urine. Results: The mean urine 5-HT concentration was significantly (P < 0.01) higher in CAD patients than in the healthy control patients. Interestingly, the excretion of the urinary 5-HT levels in CAD patients were positively associated with cigarette smoking (r = 0.411, P < 0.01), serum hs-CRP levels (r = 0.198, P < 0.05), and age (r = 0.132, P < 0.05). Conclusion: The increase in the amount of serotonin in urine in correlation with cigarette smoking, age, and hs-CRP may be important for future treatment strategies.

Increased mRNA expression of cytochrome oxidase in dorsal raphe nucleus of depressive suicide victims

Suicidal behavior is a problem with important social repercussions. Some groups of the population show a higher risk of suicide; for example, depression, alcoholism, psychosis or drug abuse frequently precedes suicidal behavior. However, the relationship between metabolic alterations in the brain and premorbid clinical symptoms of suicide remains uncertain. The serotonergic and noradrenergic systems have frequently been, implicated in suicidal behavior and the amount of serotonin in the brain and CSF of suicide victims has been found to be low compared with normal subjects. However, there are contradictory results regarding the role of noradrenergic neurons in the mediation of suicide attempts, possibly reflecting the heterogeneity of conditions that lead to a common outcome. In the present work we focus on the subgroup of suicide victims that share a common diagnosis of major depression. Based on post-mortem studies analyzing mRNA expression by in situ hybridization, serotonergic neurons from the dorsal raphe nucleus (DRN) from depressive suicide victims are seen to over-express cytochrome oxidase mRNA. However, no corresponding changes were found in the expression of tyrosine hydroxylase (TH) mRNA in the noradrenergic neurons of the Locus Coeruleus (LC). These results suggest that, despite of the low levels of serotonin described in suicide victims, the activity of DRN neurons could increase in the suicidally depressed, probably due to the over activation of serotonin re-uptake. No alteration was found in noradrenergic neurons, suggesting that they play no crucial role in the suicidal behavior of depressive patients.

Serotonin content is elevated in the immune cells of histidine decarboxylase gene knock-out (HDCKO) mice. Focus on mast cells

Biogenic amines, histamine and serotonin are present in the granules and nucleus of mast cells. We wanted to study the presence, amount and localization of serotonin in mast cells and other cells of the immune system, under conditions of histamine deficiency caused by knock out of histamine decarboxylase gene (HDCKO). Wild type and histamine deficient HDCKO mice were studied for serotonin content of the immune cells (lymphocytes as well as the monocyte-granulocyte-mast cell group) using flow cytometry and confocal microscopy. Groups of mice were kept either on complete rodent chow or on a histamine-free diet for a month before the experiments. The amount of serotonin was significantly higher in the KO animals, irrespective of the diet. Confocal microscopy demonstrated the presence of serotonin in the nucleus of mast cells in the wild type animals, while it was not present in the KO mice. Furthermore, in the cytoplasm (granules) of KO mast cells a bright fluorescence was observed in contrast to the pale fluorescence of wild animals. It seems likely that serotonin replaces the deficient histamine in the heparin-biogenic amine complex in the mast cell granules.

Alkaloid formation in cell suspension cultures of Tabernaemontana elegans after feeding of tryptamine and loganin or secologanin

A cell suspension culture of Tabernaemontana elegans lost its ability to produce alkaloids after a prolonged period of subculture. To determine whether it was still capable of performing the later steps of the alkaloid biosynthetic pathway, the culture was fed with tryptamine and loganin. The precursors and alkaloids were determined in the biomass and in the medium during a growth cycle. In this culture, an increase in the amount of serotonin was found in the biomass after feeding of tryptamine and loganin. Secologanin was detected in small amounts but strictosidine was not. Therefore, a limitation in alkaloid formation in this T. elegans cell line occured in the formation of secologanin from loganin. After feeding of secologanin alone, strictosidine, 10-hydroxy strictosidine, strictosidinic acid and two other indole alkaloids, as yet unidentified, were formed. However, the alkaloids originally produced by this cell line were not found. As the biosynthesis is impaired at several steps, it seems that the loss of productivity is more likely to be to a change on the level of the regulation of the pathway, than due to the loss of the capacity to express an individual biosynthetic gene of the pathway.

Four weeks' inhalation exposure of Long Evans rats to 4-tert-butyltoluene: effect on evoked potentials, behaviour, and brain neurochemistry.

Long-lasting central nervous system (CNS) neurotoxicity of 4-tert-butyltoluene (TBT) has been investigated using electrophysiology, behaviour, and neurochemistry in Long Evans rats exposed by inhalation to 0, 20, or 40 p.p.m. TBT 6 hr/day, 7 days/week for 4 weeks. Flash evoked potentials and somatosensory evoked potentials were not affected by TBT. In Auditory Brain Stem Response there was no shift in hearing threshold, but the amplitude of the first wave was increased in both exposed groups at high stimulus levels. Three to four months after the end of exposure, behavioural studies in Morris water maze and eight-arm maze failed to demonstrate any TBT induced effects. Exposure was followed by a 5 months exposure-free period prior to gross regional and subcellular (synaptosomal) neurochemical investigations of the brain. TBT reduced the NA concentration in whole brain minus cerebellum. Synaptosomal choline acetyltransferase activity increased and acetylcholinesterase activity was unchanged suggesting increased synaptosomal ability for acetylcholine synthesis. The relative and total yield of synaptosomal protein was reduced suggesting reduced density and total number of synapses in situ, respectively. We hypothesise that a reduced yield of synaptosomal protein reflects a more general effect of organic solvent exposure on the software of the brain. The synaptosomal concentration per mg synaptosomal protein and the total amount of 5-hydroxytryptamine were not affected whereas the total amount of synaptosomal noradrenaline decreased. The concentration and the total amount of synaptosomal dopamine decreased. The noradrenergic and dopaminergic parts of CNS may be more vulnerable to TBT than the serotonergic, and these long-lasting effects may cause or reflect TBT-compromised CNS function.