Neuronal activity regulates neurotransmitter switching in the adult brain following light-induced stress.

Neurotransmitter switching in the adult mammalian brain occurs following photoperiod-induced stress, but the mechanism of regulation is unknown. Here, we demonstrate that elevated activity of dopaminergic neurons in the paraventricular nucleus of the hypothalamus (PaVN) in the adult rat is required for the loss of dopamine expression after long-day photoperiod exposure. The transmitter switch occurs exclusively in PaVN dopaminergic neurons that coexpress vesicular glutamate transporter 2 (VGLUT2), is accompanied by a loss of dopamine type 2 receptors (D2Rs) on corticotrophin-releasing factor (CRF) neurons, and can lead to increased release of CRF. Suppressing activity of all PaVN glutamatergic neurons decreases the number of inhibitory PaVN dopaminergic neurons, indicating homeostatic regulation of transmitter expression in the PaVN.

Characteristic fingerprint spectrum of neurotransmitter norepinephrine with broadband terahertz time-domain spectroscopy.

The neurotransmitter norepinephrine (NE) was investigated by broadband terahertz time-domain spectroscopy (THz-TDS) in the air-plasma system range from 0.5 to 18.2 THz. NE has a unique absorption spectrum in the THz band, which can be used as a characteristic fingerprint for molecular detection and identification. The temperature-dependent THz spectra of NE were recorded in the range from 83 to 293 K, and a blue-shift of the absorption peaks was observed as the temperature decreased. A solid-state density functional theory (DFT) calculation was implemented to better understand the low-frequency vibrational property of NE, and the calculated results agree well with the THz experimental observations. This result suggests that the broadband THz system can obtain more abundant spectral signals of NE and each THz resonance peak has its own specific vibrational mode, which corresponds to a specific structure and interaction. Even with the adjacent absorption peaks, the vibrational behaviors are different. The deformation of the aromatic ring and the flexibility of the side chain directly affect the NE molecular conformation, which may be closely associated with the receptor binding preference for the neurotransmitter. The conformational diversity of NE may help to understand the biological function of the neurotransmitter in the nervous system.

The chronic effect of pulsed 1800 MHz electromagnetic radiation on amino acid neurotransmitters in three different areas of juvenile and young adult rat brain.

The extensive use of mobile phones worldwide has raised increasing concerns about the effects of electromagnetic radiation (EMR) on the brain due to the proximity of the mobile phone to the head and the appearance of several adverse neurological effects after mobile phone use. It has been hypothesized that the EMR-induced neurological effects may be mediated by amino acid neurotransmitters. Thus, the present study investigated the effect of EMR (frequency 1800 MHz, specific absorption rate 0.843 W/kg, power density 0.02 mW/cm2, modulated at 217 Hz) on the concentrations of amino acid neurotransmitters (glutamic acid, aspartic acid, gamma aminobutyric acid, glycine, taurine, and the amide glutamine) in the hippocampus, striatum, and hypothalamus of juvenile and young adult rats. The juvenile and young adult animals were each divided into two groups: control rats and rats exposed to EMR 1 h daily for 1, 2, and 4 months. A subgroup of rats were exposed daily to EMR for 4 months and then left without exposure for 1 month to study the recovery from EMR exposure. Amino acid neurotransmitters were measured in the hippocampus, striatum, and hypothalamus using high-performance liquid chromatography. Exposure to EMR induced significant changes in amino acid neurotransmitters in the studied brain areas of juvenile and young adult rats, being more prominent in juvenile animals. It could be concluded that the alterations in amino acid neurotransmitters induced by EMR exposure of juvenile and young adult rats may underlie many of the neurological effects reported after EMR exposure including cognitive and memory impairment and sleep disorders. Some of these effects may persist for some time after stopping exposure.

Dual-Signal Luminescent Detection of Dopamine by a Single Type of Lanthanide-Doped Nanoparticles.

Detection of dopamine, an important neurotransmitter, is vital for understanding its roles in mammals and disease diagnosis. However, commonly available methods for dopamine detection typically rely on a single signal readout, which can be susceptible to interference by internal or external factors. Here, we report a dual-signal detection of dopamine based on label-free luminescent NaGdF4:Tb nanoparticles. In the presence of dopamine, the NaGdF4:Tb nanoparticles exhibit luminescence quenching under the excitation of 272 nm, while they give enhanced luminescence under 297 nm excitation, realizing both turn off and turn on detection of dopamine. The nanoparticle-based dual-signal sensors exhibit high sensitivity, with a detection limit of ∼30 nM, and good selectivity, which offers the possibility to identify potential interferents in the samples. We further demonstrate that the dual-signal response results from different energy-transfer processes within the nanoparticles under the excitation of different light. The new strategy demonstrated here should pave the way for the development of multiresponse nanosensors based on lanthanide-doped luminescent nanomaterials.

Caged neurotransmitters. Shedding light on neural circuits.

The ability to locally activate neurons in living brain slices by using light to release 'caged' neurotransmitter allows the organization and development of neural circuits to be studied at a hitherto impossible level of detail.

Pulsed radiofrequency applied to dorsal root ganglia causes a selective increase in ATF3 in small neurons.

BACKGROUND: This is a "proof of concept study" to test the hypothesis that pulsed radiofrequency, PRF, produces cell stress at the primary afferent level without signs of overt thermal damage. We assumed that cell stress would result in impairment of normal function, and used the expression of activating transcription factor 3, ATF3, as an indicator of cellular "stress". METHODS: PRF (20 ms of 500-kHz RF pulses, delivered at a rate of 2 Hz; maximum temperature 42 degrees C) was delivered either to the sciatic nerve of adult rats in mid thigh, or to the L4 anterior primary ramus just distal to the intervertebral foramen. Controls were sham-operated or L4 axotomised. All tissues were examined 14 days after surgery. The percentage of CGRP- or ATF3-positive DRG neuronal somata was calculated using image analysis software (SigmaScan Pro 4). RESULTS: ATF3 expression was upregulated in L4 DRG neuronal cell bodies, irrespective of their size, after axotomy. It was also upregulated significantly (p<0.002) and selectively, in small and medium calibre L4 DRG neurons, when PRF was applied close to the DRG just distal to the intervertebral foramen. PRF did not produce any obvious cellular changes in the nerve or L4 DRG neurons when applied to the sciatic nerve in mid-thigh. CONCLUSION: PRF has a biological effect, unlikely to be related to overt thermal damage. It appears to be selective in that it targets the group of neurons whose axons are the small diameter C and Adelta nociceptive fibres.

Mechanisms of radiation-induced conditioned taste aversion learning.

The literature on taste aversion learning is reviewed and discussed, with particular emphasis on those studies that have used exposure to ionizing radiation as an unconditioned stimulus to produce a conditioned taste aversion. The primary aim of the review is to attempt to define the mechanisms that lead to the initiation of the taste aversion response following exposure to ionizing radiation. Studies using drug treatments to produce a taste aversion have been included to the extent that they are relevant to understanding the mechanisms by which exposure to ionizing radiation can affect the behavior of the organism.

Current status and perspectives of research on radiation hormesis in Japan.

The CRIEPI initiated the Radiation Hormesis Research based on the following rationale. If the Luckey's claim was true, our daily activities in the radiation management would be extremely erroneous. If the Luckey's claim was false, the concept publicated would bring us serious disturbance on the radiation management in Japan. We organized a hormesis research steering committee by the specialists in the concerned field, and started researches under cooperation with many universities, National Cancer Center Research Institute, and National Institute of Radiological Sciences. After interesting results obtained by various experiments on the health effects by low dose, we are now proceeding on the Round Robin tests program including fifteen research plans with universities all over Japan. These activities are categorized as: A. Effects of free radicals produced by the low dose radiation; B. Molecular biological responses to the low dose radiation; C. Radiation effects on the neurotransmission system; D. Stimulative effects of low dose radiation on the immune systems; and E. Epidemiological studies.

[The reaction of the systems of hormonal mediator regulation to a weak geomagnetic field against a background of ionizing radiation exposure]. / Reaktsiia sistem gormonal'no-mediatornoi reguliatsii na gipogeomagnitnoe pole na fone vozdeistviia ioniziruiushchego izlucheniia.

Guinea pigs were subjected for 30 minutes to geomagnetic field of ten times decreased induction. The increase of epinephrine and histamine level in blood was observed. The decrease of histamine and serotonin concentration as well as normalization of epinephrine level were found when the influence of weakened geomagnetic field was stopped. Preliminary 2 Gy X-radiation resulted in the suppressed response of the organism to the weak geomagnetic field.

[Neurotransmitter balance in the CNS structure as effected by the combination of ionizing radiation and various doses of lead acetate]. / Neiromediatornyi balans v strukturakh TsNS pri sochetannom vozdeistvii ioniziruiushchei radiatsii i razlichnykh doz atsetata svintsa.

In experiments with mature Wistar male rats exposed to 25- and 50-fold fractionated doses of external X-ray radiation (0.5 Gy) and daily probe-assisted administration of plumbum acetate (100, 10, 5 mg/kg), similar, but differently marked changes in transmitter relationship in some CNS structures resembling the earlier found neurotransmitter disbalance during chronic stress of different ethiology were revealed. Combined exposure to plumbum and radiation led to more sustained and prolonged disorders to transmitter relationship associated with a sharp decrease in specific binding of corticosterone in CNS glucocorticoid-sensitive structures.

[The neuromediator modulation of the ionic composition of the brain cells in rats irradiated at nonlethal doses]. / Neiromediatornaia moduliatsiia ionnogo sostava kletok golovnogo mozga krys pri obluchenii v neletal'nykh dozakh.

It had been found that both the single prolonged irradiation and chronic (fractionated) one with doses of 25 and 50 cGy (1.75 mGy/min) caused essential modification of the biphase modulative effects of acetylcholine and gamma-aminobutyric acid upon K+ level in rat brain cortex slices to be compared to the acute lethal irradiation influence. The results of model experiments showed saturated fatty acids to be significant for the changes in regulative functions of nerve cell membranes after exposure to low dose-rate radiation.

Effect of 1440-nanometer neodymium:yttrium-aluminum-garnet laser irradiation on pain and neuropeptide reduction: a randomized prospective clinical trial.

INTRODUCTION: The purpose of this study was to investigate the efficacy of a 1440-nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser on relieving pain in relation to the levels of inflammatory cytokine and neuropeptides in the root canal exudates of teeth with persistent symptomatic apical periodontitis. METHODS: Forty teeth with persistent symptomatic apical periodontitis were randomly assigned to treatment groups: group L, intracanal irradiation of 1440-nm Nd:YAG laser with a 300-µm-diameter fiberoptic tip in addition to conventional root canal retreatment, and group C, conventional root canal re-treatment. The degrees of both spontaneous pain and the pain on percussion before and after treatment were recorded, and root canal exudate samples were collected to quantify the associated levels of substance P, calcitonin gene-related peptide (CGRP), and matrix metalloproteinase (MMP)-8 by immunoassay. RESULTS: All of the measured parameters were significantly reduced in group L (P < .05), whereas the level of pain on percussion, CGRP, and MMP-8 were significantly reduced in group C (P < .05). The 1440-nm Nd:YAG laser had significantly better effect on the relief of pain on percussion and the reduction of substance P, CGRP, and MMP-8 levels. The visual analog scale scores of perceived pain correlated with pain-related neuropeptides and inflammatory cytokine levels in root canal exudates. CONCLUSIONS: The 1440-nm Nd:YAG laser irradiation via fiberoptic tip to the teeth with persistent apical periodontitis provided promising consequences of pain and inflammation modulation.

Photolysis of caged neurotransmitters: theory and procedures for light delivery.

Photolysis of "caged" compounds is a technique for releasing biologically active compounds in which the timing, rate, and spatial profile of release are controlled by light. Issues relating to the delivery of light for single-photon photolysis are presented. Specific discussions include the theories relating to how light interacts with biological tissue to produce scattering and phototoxicity, as well as the issues involved in choosing the appropriate light source. Several approaches and optical designs are presented for delivering the output of a laser to a microscopic specimen. The criteria for choosing an approach are presented. The commercial sources for the parts needed to build a photolysis system are also provided. This unit will be particularly useful for investigators interested in single-photon photolysis of caged neurotransmitters in brain slices.

Magnetization transfer effect on human brain metabolites and macromolecules.

A pulse sequence was implemented to observe the magnetization transfer (MT) effect on metabolites, water, and macromolecules in human frontal lobes in vivo at 1.5 Tesla. Signals were compared following the application of three hard pulses of 0.745 muT amplitude, applied at frequency offsets of either 2500 Hz or 30 kHz, preceding a conventional point-resolved spectroscopy (PRESS)-localized acquisition with an echo time (TE) of 30 ms and repetition time (TR) of 3 s. This gave an MT effect on water in vivo of 46%, while direct saturation by the MT pulses at 2.5 kHz offset was confirmed to be under 4% for all metabolites. We observed significant MT saturation in vivo for N-acetylated compounds, choline (Cho), myo-inositol, and lactate (Lac); a trend of an effect on glutamate + glutamine (Glx); and the typically observed effect on creatine (Cr). No significant MT effect was seen on the macromolecule signal, which was observed using metabolite nulling.

Radiation effects on dopamine and norepinephrine.

PURPOSE: Radiation sterilization is becoming increasingly popular for the sterilization of many pharmaceutical products. We have investigated the gamma radiation induced effects on dopamine and norepinephrine by ESR spectroscopy. RESULTS AND DISCUSSION: Equations to describe the evolution of the ESR curves versus doses and time of storage are presented. Linear regression is, for dopamine hydrochloride, applicable for doses ranging from 10 to 25 kGy. Since the radiation dose selected must always be based upon the bioburden of the products and the degree of sterility required, doses in the range 10-25 kGy could be investigated and linear regression would appear to be the least expensive route to follow and gives good results. The comportment of noradrenaline bitartrate is more complex and the use of linear regression would appear more hazardous especially for low doses. For doses higher than 25 kGy, a more general equation is required. Power function using only 2 parameters could give good results but must be validated. Decay kinetics for radicals versus storage were considered. Non-homogeneous kinetics with time dependent rate constant and bi-exponential function appeared valid to reproduce the decay of radicals for, respectively, dopamine and norepinephrine. CONCLUSIONS: It is worth noting that, at present, ESR is the only technique which proved to be suitable for identification and quantification purposes in irradiated pharmaceuticals. Moreover, other features such as sensitivity, precision, ease and non-destructive readout make ESR superior to other proposed analytical techniques.

Chronic exposure of primates to 60-Hz electric and magnetic fields: II. Neurochemical effects.

We exposed Macaca nemestrina (pig-tailed macaques) to electric (E) and magnetic (B) fields ranging in intensity from 3 kV/m and 0.1 G to 30 kV/m and 0.9 G for three 21-day (d) periods. Experimental animals were exposed to sham E and B fields for two 21-d periods, one prior to and one following actual exposure to E and B fields, resulting in a total of five 21-d periods. Control animals were exposed to sham E and B fields for the entire 105-d interval. At the end of each 21-d period cerebrospinal fluid (CSF) was obtained by lumbar puncture and analyzed for concentrations of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), metabolites of dopamine and serotonin neurotransmitters, respectively, by high-performance liquid chromatography with electrochemical detection (HPLC-ECD). Results are based on an examination of six experimental and four control animals. Exposure to E and B fields at all strengths was associated with a significant decline in CSF concentrations of both HVA and 5-HIAA when statistical comparisons were made against values obtained at the end of the preexposure interval. However, HVA returned to preexposure levels during the postexposure period, while 5-HIAA did not. No significant change in the concentrations of HVA or 5-HIAA was noted in the control animals. These results strongly suggest that exposure of the nonhuman primate to E and B fields can significantly affect specific biochemical estimates of nervous system function. These effects may involve alterations either in neuronal activity or in the activity of enzymes that catabolize the neurotransmitters.