Effect of Short-term 900 MHz low level electromagnetic radiation exposure on blood serotonin and glutamate levels.

BACKGROUND: Long term exposure to low level electromagnetic radiation (LLER) by using cellular phones causes serious health problems. METHODS: Ten male Wistar Albino rats were anesthetized 30 min before the LLER exposure, 0.5 ml blood was taken from the tail vein of rats in order to determine control values. Rats were grouped by three and placed on a plexi-glass flat. A fixed equivalent frequency emitter device was used. A sign to be an electromagnetic field 15.14 V/m (608 mW/m(2)) in strength in the head region with 100 kHz FM modulation at 900 MHz was applied to the animals. After calculating the ideal position for the device, electromagnetic LLER energy was applied for 45 minutes from a distance to be equal with energy transmitted by a mobile phone from a 0.5-1 cm distance to their head regions. After 1.5 hours and before the rats awoke, 0.5 ml of blood was taken from the tail veins in order to determine the treatment values. RESULTS: Plasma 5-HT and glutamate levels were measured by enzyme immunoassay (EIA) using commercial kits. It was found that a single 45 min of LLER exposure increased the blood 5-HT level significantly, but did not change the glutamate level of rats. CONCLUSION: It was concluded that even a single 45 min of LLER exposure may produce an increase in 5-HT level without changing the blood glutamate level. Increased 5-HT level may lead to a retarded learning and a deficit in spatial memory (Tab. 2, Fig. 2, Ref. 24).

On the generation and quenching of reactive-oxygen-species by aqueous vitamin B2 and serotonin under visible-light irradiation.

It is well known that endogenous daylight-absorbing compounds produce the sensitized photodegradation of biologically relevant substrates. In this context the photostability of a mixture of the indole neurotransmitter serotonin (Sero) and vitamin B2 (riboflavin, Rf) upon visible-light irradiation and the possible role of Sero and related compounds as generators or deactivators of reactive oxygen species (ROS) was investigated through a kinetic and mechanistic study. The work was done at pH 7 and under experimental conditions in which only the vitamin absorbs photoirradiation. Tryptamine (Trpa) and 5-hydroxyindole (OHIn) were included in the study as model compounds for the neurotransmitter. The visible light irradiation of aqueous Rf in the individual presence of Sero, Trpa and 5-OHIn, under aerobic conditions, induce degradative processes on the indole derivatives (In-der). At least two different mechanisms operate. Our analysis shows that the main reaction pathway is an electron-transfer-mediated quenching of triplet excited Rf ((3)Rf(*)) by the In-der. It produces the species Rf(-)/RfH() and the In-der radical cation that could react to form phenoxy and α-amino radicals. In a further reaction step the species O(2)(-) and OH() could be produced. In parallel, energy transfer from (3)Rf(*) to dissolved oxygen would generate O(2)((1)Δ(g)). Within the frame of the proposed mechanism, results suggest that Rf-sensitized degradation of Sero occurs via the mentioned ROS and non-oxygenated radical-mediated processes. The indole compound quenches O(2)((1)Δ(g)) in a dominant physical fashion. This fact constitutes a desirable property in antioxidants, provided that the quenching process practically does not eliminate the scavenger. Sero exerts a photoprotective effect towards tryptophan through the combined quenching of O(2)((1)Δ(g)) and (3)Rf(*), the latter excited species responsible for the generation of ROS. The amino acid can be taken as a target model of oxidizable biological substrates, particularly proteins.

Serotonin accumulation in transgenic rice by over-expressing tryptophan decarboxylase results in a dark brown phenotype and stunted growth.

A mutant M47286 with a stunted growth, low fertility and dark-brown phenotype was identified from a T-DNA-tagged rice mutant library. This mutant contained a copy of the T-DNA tag inserted at the location where the expression of two putative tryptophan decarboxylase genes, TDC-1 and TDC-3, were activated. Enzymatic assays of both recombinant proteins showed tryptophan decarboxylase activities that converted tryptophan to tryptamine, which could be converted to serotonin by a constitutively expressed tryptamine 5' hydroxylase (T5H) in rice plants. Over-expression of TDC-1 and TDC-3 in transgenic rice recapitulated the stunted growth, darkbrown phenotype and resulted in a low fertility similar to M47286. The degree of stunted growth and dark-brown color was proportional to the expression levels of TDC-1 and TDC-3. The levels of tryptamine and serotonin accumulation in these transgenic rice lines were also directly correlated with the expression levels of TDC-1 and TDC-3. A mass spectrometry assay demonstrated that the darkbrown leaves and hulls in the TDC-overexpressing transgenic rice were caused by the accumulation of serotonin dimer and that the stunted growth and low fertility were also caused by the accumulation of serotonin and serotonin dimer, but not tryptamine. These results represent the first evidence that over-expression of TDC results in stunted growth, low fertility and the accumulation of serotonin, which when converted to serotonin dimer, leads to a dark brown plant color.

Reduction of type II taste cells correlates with taste dysfunction after X-ray irradiation in mice.

BACKGROUND: Taste dysfunction that develops after radiotherapy for head and neck cancer impairs patients' quality of life. Although taste cells have been shown to degenerate after exposure to X-ray irradiation, the alteration in taste cell population is unclear. This study investigated the histopathological change of taste bud structure and the taste cell population in X-ray irradiated mice. METHODS: The head and neck region of C57BL/6J male mice was exposed to a single 15 Gy dose of X-ray irradiation and a chronological histopathological analysis of the circumvallate papilla was performed. Preference for sweet taste was measured using the two-bottle preference method. RESULTS: The histological analysis of the circumvallate papilla revealed that the basal cells had almost disappeared, but that there was not clear change in the spindle-shaped taste cells on day 4 after irradiation. The number of taste cells had decreased on day 8, and then remained unchanged until day 20, after which they increased and recovered to their original number by day 24. There was a more marked decrease in the number of alpha-gustducin-positive type II taste cells than in the number of serotonin-positive type III taste cells. Preference for sweet taste measured by the two-bottle preference method was decreased in parallel with taste cell number. CONCLUSION: These findings suggest that X-ray irradiation disrupts the basal cells, resulting in a decrease of the number of taste cells, particularly type II taste cells, which may be the cause of radiotherapy-induced taste dysfunction.

The influence of daylight exposure on platelet 5-HT levels in patients with major depression and schizophrenia.

Platelet serotonin (5-HT) can be used as a limited, peripheral model for the central 5-HT synaptosomes. Altered platelet 5-HT concentrations have been associated with psychiatric disorders like depression and schizophrenia. The aim of the present study was to compare platelet 5-HT concentrations during long, medium and short period of natural daylight exposure in a large number of medication-free male and female schizophrenic and depressed patients and sex-matched healthy controls. Platelet 5-HT concentration was determined spectrofluorimetrically in 240 (97 female, 143 male) schizophrenic and 258 (153 female, 105 male) nonpsychotic, nonsuicidal depressed medication-free patients and 328 (149 women, 179 men) healthy subjects during periods with short (<12), long (>12) and medium (average 12) hours of the natural daylight. Platelet 5-HT concentration was significantly lower in women compared to men in all groups. Healthy male subjects had significantly higher (p=0.011) platelet 5-HT concentrations during long compared to medium period. There were no significant differences (p>0.05) in platelet 5-HT concentration between different periods in healthy women. The significant increase in platelet 5-HT values were found in female (p=0.01) and male (p=0.029) depressed patients during long compared to short period. There were no significant associations between platelet 5-HT concentrations and different periods in both male and female schizophrenic patients. The results indicate the sex-related differences in the serotonergic system. The alterations of platelet 5-HT concentrations, observed across period with different durations of daylight exposure, point to a direct or indirect effect of light on peripheral 5-HT system that could be related to different sensitivity of the pineal gland to light and/or melatonin influence on 5-HT metabolism.

Single- and multi-photon excited fluorescence from serotonin complexed with beta-cyclodextrin.

The fluorescence of serotonin on binding with beta-cyclodextrin has been studied using both steady state and time-resolved methods. Steady state fluorescence intensity of serotonin at 340 nm showed approximately 30% increase in intensity on binding with K(A) approximately 60 dm(3) mol(-1) and the fluorescence lifetimes showed a corresponding increase. In contrast, the characteristic green fluorescence ('hyperluminescence') of serotonin observed upon multiphoton near-infrared excitation with sub-picosecond pulses was resolved into two lifetime components assigned to free and bound serotonin. The results are of interest in relation to selective imaging and detection of serotonin using the unusual hyperluminescence emission and in respect to recent determinations of serotonin by capillary electrophoresis in the presence of cyclodextrin. The results also suggest that hyperluminescence occurs from multiphoton excitation of a single isolated serotonin molecule.

Repetitive transcranial magnetic stimulation improves open field locomotor recovery after low but not high thoracic spinal cord compression-injury in adult rats.

Electromagnetic fields are able to promote axonal regeneration in vitro and in vivo. Repetitive transcranial magnetic stimulation (rTMS) is used routinely in neuropsychiatric conditions and as an atraumatic method to activate descending motor pathways. After spinal cord injury, these pathways are disconnected from the spinal locomotor generator, resulting in most of the functional deficit. We have applied daily 10 Hz rTMS for 8 weeks immediately after an incomplete high (T4-5; n = 5) or low (T10-11; n = 6) thoracic closed spinal cord compression-injury in adult rats, using 6 high- and 6 low-lesioned non-stimulated animals as controls. Functional recovery of hindlimbs was assessed using the BBB locomotor rating scale. In the control group, the BBB score was significantly better from the 7th week post-injury in animals lesioned at T4-5 compared to those lesioned at T10-11. rTMS significantly improved locomotor recovery in T10-11-injured rats, but not in rats with a high thoracic injury. In rTMS-treated rats, there was significant positive correlation between final BBB score and grey matter density of serotonergic fibres in the spinal segment just caudal to the lesion. We propose that low thoracic lesions produce a greater functional deficit because they interfere with the locomotor centre and that rTMS is beneficial in such lesions because it activates this central pattern generator, presumably via descending serotonin pathways. The benefits of rTMS shown here suggest strongly that this non-invasive intervention strategy merits consideration for clinical trials in human paraplegics with low spinal cord lesions.

Multiphoton-excited visible emission by serotonin solutions.

Nonlinear excitation of the neurotransmitter serotonin (5HT) in aqueous solution is shown to generate a blue-green-emitting photoproduct in addition to UV fluorescence characteristic of native 5HT. The visible emission rate in diffusional steady-state measurements scales as the sixth power of excitation intensity, demonstrating that absorption of six near-IR photons is required to generate emission of one visible photon. Transient measurements reveal that this process is composed of two sequential nonlinear steps, the first excited by four photons and the second by two photons. These results, in combination with measurements of multiphoton-excited serotonin UV fluorescence, support a model in which 5HT is photochemically transformed as a consequence of four-photon absorption (Etot approximately 6 eV) to a photoproduct that then emits in the visible region via two-photon excitation. A minimum bound of approximately 10(-51) cm4 s photon-1 is observed for the two-photon emission action cross section at 830 nm. Photoionization, rather than reaction with a dissolved oxygen species, appears to be the primary mechanism for generation of the blue-green-emitting photoproduct. The peak intensities required to generate significant blue-green emission (approximately 5 x 10(11) W cm-2 from 80 MHz 150 fs titanium: sapphire laser pulses) are approximately five-fold higher than are typically used in two-photon laser scanning microscopy but are still substantially lower than the estimated intensity needed to induce dielectric breakdown of water.

Photophysics of a neurotransmitter: ionization and spectroscopic properties of serotonin.

The neurotransmitter serotonin plays a modulatory role in the regulation of various cognitive and behavioral functions such as sleep, mood, pain, depression, anxiety, and learning by binding to a number of serotonin receptors present upon the cell surface. The spectroscopic properties of serotonin and their modulation with ionization state have been studied. Results show that serotonin fluorescence, as measured by its intensity, emission maximum, and lifetime, is pH dependent. These results are further supported by absorbance changes that show very similar pH dependence. Changes in fluorescence intensity and absorbance as a function of pH are consistent with a pK(a) of 10.4 +/- 0.2. The ligand-binding site for serotonin receptors is believed to be located in one of the transmembrane domains of the receptors. To develop a basis for monitoring the binding of serotonin to its receptors, its fluorescence in nonpolar media has been studied. No significant binding or partitioning of serotonin to membranes under physiological conditions was observed. Serotonin fluorescence in solvents of lower polarity is characterized by an enhancement in intensity and a blue shift in emission maximum, although the solvatochromism is much less pronounced than in tryptophan. In view of the multiple roles played by the serotonergic systems in the central and peripheral nervous systems, these results are relevant to future studies of serotonin and its binding to its receptors.

[An experimental study of the effect of Zofran on the manifestations of a primary reaction to irradiation]. / Eksperimental'noe issledovanie vliianiia zofrana na proiavleniia pervichnoi reaktsii na obluchenie.

Zofran is a selective antagonist of 5-HT3 receptors which effectively prevents postradiation dyspeptic and behavioral disorders in dogs and rats. Administration of the drug normalizes intestinal absorption and propulsion activity in irradiated animals.

Changes of aggressive behavior and brain serotonin turnover after very low-dose X-irradiation of mice.

Social isolation has been widely described to induce compulsive aggressive behavior and produce a large decrease of brain serotonin turnover in male mice. The aggressiveness by isolation in mice has been often used as a means for a better understanding of disturbed behavior in human beings. We found that male ICR white Swiss mice exhibiting isolation-induced aggression became gradually calm and showed remarkably quiet behavior 7 to 10 days after whole body irradiation of very low-dose X-rays (5-15 cGy). Higher doses (25-35 cGy), however, could not induce such effects. We also obtained the data on brain biochemistry giving a further support for the above low-dose effects on the mouse behavior. Brain serotonin turnover which has been known to be related to aggressive behavior in 5 or 15 cGy irradiated mice was faster than in aggressive control animals.

[The effect of an increased intensity of light on changes in the serotonin and melatonin content in patients with depression]. / Vliianie sveta povyshennoi intensivnosti na izmenenie soderzhaniia serotonina i melatonina u bol'nykh s depressiei.

Study into the effect of light of increased intensity shows that in patients with anxious depression a high level of melatonin excretion declines to normal, its low level in melancholic depression remaining unchanged. Blood concentrations of serotonin in depressive patients are higher as compared with the healthy persons and do not change with increasing in the brightness of the illumination except for a decrease in a portion of patients showing maximum levels of serotonin and melanin.

[The effect of long-term 24-hour illumination on serotonin metabolism in the rat epiphysis]. / Vliianie dlitel'nogo kruglosutochnogo osveshcheniia na metabolizm serotonina v épifize krys.

Continuous illumination of pubertal rats during their 1st month of life induced metabolism of serotonin in the pineal gland. This seems to be the basis of the mechanism by means of which the pineal gland interferes in the processes of biological rhythms photoregulation.

Pineal gland "magnetosensitivity" to static magnetic fields is a consequence of induced electric currents (eddy currents).

During the past decade, a number of reports indicated that the mammalian pineal gland is magnetosensitive in terms of spatial orientation. This indication is based on observations that artificial alterations of the direction of the earth's magnetic field (MF) markedly decreased the gland's capability to synthesize melatonin. These findings, however, seem paradoxical since animals as well as humans experience such alterations whenever they turn their heads. Therefore, the potential of the pineal for sensing magnetic fields was re-investigated. During the dark phase, rats were exposed to repeatedly inverted MFs, generated by two identical pairs of Helmholz coils; one pair connected to a power supply automatically, the other pair manually using an integrated potentiometer. Only the pineals of animals exposed to the automatically activated field responded with a reduced activity of the rate-limiting enzyme serotonin-N-acetyltransferase, lower melatonin levels and increases in serotonin and 5-hydroxyindole acetic acid. Hence, MF exposure itself did not affect the pineal. Rather, induced eddy currents in the animals, resulting from rapid On/Off transients of the artificially applied MF, are most likely the explanation.

[Pyridoxal phosphate as an agent for normalizing the monoamine oxidase activity of the brain in radiation sickness]. / Piridoksal'fosfat kak sredstvo normalizatsii monoaminoksidaznoi aktivnosti golovnogo mozga pri luchevoi bolezni.

A study was made of the influence of the coenzyme pyridoxal phosphate on the activity of mitochondrial monoaminoxidase (MAO) catalyzing oxidative deamination of serotonin at the exacerbation of acute radiation disease (on the 6th day after radiation exposure) in different parts of the brain (cerebral hemisphere, stem and cerebellum). Experiments were staged on rabbits, irradiated by x-ray at a dose of 4.5 Gy with a dose rate of 0.33 Gy/min. The peak of radiation disease was characterized by considerable changes in MAO activity resulting in catalysis of oxidative deamination of serotonin in different parts of the brain and in different mitochondrial subfractions. Pyridoxal phosphate produced a positive effect on monoaminoxidase activity, catalyzing serotonin deamination, and as a coenzyme it can be incorporated in a complex of drugs used for normalization of metabolism of mediators of the nervous system as well as for therapy of radiation injuries.

[The effect on an impulse electromagnetic field on the bioamine allowance of the spinal ganglion in rats under whole-body exposure]. / Vliianie impul'snogo élektromagnitnogo polia na sostoianie bioaminnoi obespechennosti spinnomozgovogo gangliia krys v usloviiakh total'nogo vozdeistviia.

In experiments with albino male rats subjected to whole-body pulse electromagnetic irradiation of 100 mTl magnetic induction, the luminescent histochemical methods and the subsequent microspectrofluorometry were used to determine the content of biogenic amines (catecholamines, serotonin, and histamine) in spinal ganglia neurons. Significant changes were revealed not only in the content of all studied bioamines but in the histamine/serotonin ratio as well.

On the interaction between 5-hydroxytryptamine and N-acetylneuraminic acid under aqueous conditions.

A complex designated 5-HT-NeuAc was formed between 5-hydroxytryptamine (5-HT) and N-acetylneuraminic acid (NeuAc) under aqueous conditions. Complex formation was encouraged by exposure to light (3000-3800 A; 1 A = 0.1 nm) and freeze-drying and the freeze-dried complex was isolated by gel filtration chromatography. Although stable to rechromatography on Bio-Gel P-2 if H2O was the eluent, 5-HT-NeuAc dissociated into the free components when placed in 0.1 M NaCl. Chemical analyses of the isolated complex showed that an equimolar amount of 5-HT and NeuAc was present and that all group functions were intact; these data suggested that the association between 5-HT and NeuAc was noncovalent. Spectrophotometric measurements demonstrated a small increase (approximately 12%) in extinction coefficient (275 nm) and a large increase (340- to 440-fold) in fluorescence emission (340 nm) compared with 5-HT alone. Data obtained from 1H nuclear magnetic resonance spectroscopy (250 MHz) of 5-HT and NeuAc standards compared closely to published reports. In comparison, measurements made with 5-HT-NeuAc showed that all 5-HT protons were slightly deshielded; of the NeuAc protons, slight deshielding of H8 and significant shielding of H3eq, H3ax, and H6 was observed. From these observations, a model describing the association between 5-HT and NeuAc is proposed.

[Effect of the photo-induced synthesis of serotonin on the photoreactivation of Saccharomyces cerevisiae yeasts]. / O vliianii fotoindutsirovannogo sinteza serotonina na fotoreaktivatsiiu drozhzhei Saccharomyces cerevisiae.

The photoreactivation of yeast (Saccharomyces cerevisiae) cells irradiated by far-UV-light has been studied. It has been shown that the near-UV-induced (334, 365 nm) synthesis of serotonin in yeast is an underlying cause of its photoreactivation action spectrum change. The effect of serotonin is due to its binding to far-UV-irradiated DNA (pyrimidine dimers) making them unavailable to the photoreactivating enzyme. The data obtained support the idea that serotonin affects the repair enzymes which are engaged in an elimination of lethal photoproducts from DNA.