Long-term exposure to ELF-MF ameliorates cognitive deficits and attenuates tau hyperphosphorylation in 3xTg AD mice.

Although numerous studies have reported the influence of extremely low frequency magnetic field (ELF-MF) exposure on human health, its effects on cognitive deficits in Alzheimer's disease (AD) have remained under debate. Moreover, the influence of ELF-MF on hyperphosphorylated tau, which is one of the most common pathological hallmarks of AD, has not been reported to date. Therefore, transgenic mice (3xTg) were used in the present study. 3xTg mice, which express an APP/PS1 mutation combined with a tau (P301L) mutation and that develop cognitive deficits at 6 months of age, were subjected to ELF-MF (50Hz, 500µT) exposure or sham exposure daily for 3 months. We discovered that ELF-MF exposure ameliorated cognitive deficits and increased synaptic proteins in 3xTg mice. The protective effects of ELF-MF exposure may have also been caused by the inhibition of apoptosis and/or decreased oxidative stress levels that were observed in the hippocampus tissues of treated mice. Furthermore, tau hyperphosphorylation was decreased in vivo because of ELF-MF exposure, and this decrease was induced by the inhibition of GSK3ß and CDK5 activities and activation of PP2Ac. We are the first to report that exposure to ELF-MF can attenuate tau phosphorylation. These findings suggest that ELF-MF exposure could act as a valid therapeutic strategy for ameliorating cognitive deficits and attenuating tau hyperphosphorylation in AD.

Repeated exposure attenuates the behavioral response of rats to static high magnetic fields.

Exposure of rats to high strength static magnetic fields of 7 T or above has behavioral effects such as the induction of locomotor circling, the suppression of rearing, and the acquisition of conditioned taste aversion (CTA). To determine if habituation occurs across magnetic field exposures, rats were pre-exposed two times to a 14 T static magnetic field for 30 min on two consecutive days; on the third day, rats were given access to a novel 0.125% saccharin prior to a third 30-min exposure to the 14 T magnetic field. Compared to sham-exposed rats, pre-exposed rats showed less locomotor circling and an attenuated CTA. Rearing was suppressed in all magnet-exposed groups regardless of pre-exposure, suggesting that the suppression of rearing is more sensitive than other behavioral responses to magnet exposure. Habituation was also observed when rats underwent pre-exposures at 2-3h intervals on a single day. Components of the habituation were also long-lasting; a diminished circling response was observed when rats were exposed to magnetic field 36 days after 2 pre-exposures. To control for possible effects of unconditioned stimulus pre-exposure, rats were also tested in a similar experimental design with two injections of LiCl prior to the pairing of saccharin with a third injection of LiCl. Pre-exposure to LiCl did not attenuate the LiCl-induced CTA, suggesting that 2 pre-exposures to an unconditioned stimulus are not sufficient to explain the habituation to magnet exposure. Because the effects of magnetic field exposure are dependent on an intact vestibular apparatus, and because the vestibular system can habituate to many forms of perturbation, habituation to magnetic field exposure is consistent with mediation of magnetic field effects by the vestibular system.

Zingiber officinale exhibits behavioral radioprotection against radiation-induced CTA in a gender-specific manner.

At the organismic level, exposure to radiation can produce taste aversion (CTA) learning and emesis, which have been proposed as behavioral endpoints that are mediated by harmful effects of radiations on peripheral systems, primarily the gastrointestinal system. Thus, the aim of the present investigation was to study the gastroprotective action of hydroalcoholic extract of zingiber rhizome (Zingiber officinale Rosc.) against radiation-induced conditioned taste aversion (CTA) in both male and female species of animals, for testing its potential as a behavioral radioprotector. Administration of zingiber extract 1 h before 2-Gy gamma-radiation was significantly effective in blocking the saccharin avoidance response, with 200 and 250 mg/kg b.wt. i.p., being the most effective doses for male and female rats, respectively. A comparison of the efficacy of zingiber extract with two antiemetic drugs, ondansteron and dexamethasone, revealed that the extract rendered comparable protection against radiation-induced CTA. Our experiments also confirmed the existence of sex dichotomy (i.e., the sex of animal greatly influenced response towards radiation exposure) in relation to behavioral responses (CTA) or differential metabolism. The observed gender variations were hypothesized to be a result of hormonal fluctuations and differences in pharmacological parameters in male and female rats. To correlate the mechanism of action, the free-radical-scavenging potential of zingiber extract to scavenge hydroxyl ion and nitric oxide was also tested, in cell-free system and a concentration of 1000 microg/ml, was found to be the most potent, which has been proposed as one the many activities assisting in its overall ability to modulate radiation-induced taste aversion. The results demonstrate that Z. officinale possesses antioxidant, radioprotective and neuromodulatory properties that can be effectively utilized for behavioral radioprotection and for efficiently mitigating radiation-induced CTA in both males and females species.

Zingiber officinale Rosc. modulates gamma radiation-induced conditioned taste aversion.

The aim of the present study was to investigate the neurobehavioral protective efficacy of a hydroalcoholic extract of ginger (Zingiber officinale Rosc.) in mitigating gamma radiation-induced conditioned taste aversion in Sprague-Dawley rats. Administration of Zingiber extract 1 h before 2-Gy gamma irradiation was effective in blocking the saccharin avoidance response for 5 post-treatment observational days, both in a dose- and time-dependent manner, with 200 mg/kg b.w. i.p. being the most effective dose. Highest saccharin intake in all the groups was observed on the fifth post-treatment day. The potential of ginger extract to inhibit lipid peroxidation induced by radiation (2 Gy) and ascorbate-ion stress in brain homogenate and its ability to scavenge highly reactive superoxide anions were evaluated. The 1000-microg/ml and 2000-microg/ml concentration of ginger extract showed the highest efficiency in scavenging free radicals and in inhibiting lipid peroxidation. The lipid peroxidation and superoxide-anion scavenging ability of the extract further supports its radioprotective properties. The results clearly establish the neurobehavioral efficacy of ginger extract and the antioxidant properties appear to be a contributing factor in its overall ability to modulate radiation-induced conditioned taste aversion. Ginger extract has tremendous potential for clinical applications in mitigation of radiation-induced emesis in humans.

The effects of proton exposure on neurochemistry and behavior.

Future space missions will involve long-term travel beyond the magnetic field of the Earth, where astronauts will be exposed to radiation hazards such as those that arise from galactic cosmic rays. Galactic cosmic rays are composed of protons, alpha particles, and particles of high energy and charge (HZE particles). Research by our group has shown that exposure to HZE particles, primarily 600 MeV/n and 1 GeV/n 56Fe, can produce significant alterations in brain neurochemistry and behavior. However, given that protons can make up a significant portion of the radiation spectrum, it is important to study their effects on neural functioning and on related performance. Therefore, these studies examined the effects of exposure to proton irradiation on neurochemical and behavioral endpoints, including dopaminergic functioning, amphetamine-induced conditioned taste aversion learning, and spatial learning and memory as measured by the Morris water maze. Male Sprague-Dawley rats received a dose of 0, 1.5, 3.0 or 4.0 Gy of 250 MeV protons at Loma Linda University and were tested in the different behavioral tests at various times following exposure. Results showed that there was no effect of proton irradiation at any dose on any of the endpoints measured. Therefore, there is a contrast between the insignificant effects of high dose proton exposure and the dramatic effectiveness of low dose (<0.1 Gy) exposures to 56Fe particles on both neurochemical and behavioral endpoints.

High illumination levels potentiate the acoustic startle response in preweanling rats.

Fear potentiation of the acoustic startle response (FPS) by aversive conditioned stimuli does not emerge in rats until Postnatal Day (P)23 (see P. S. Hunt & B. A. Campbell, 1997). However, the present study found that when presented with an unconditioned fear-eliciting stimulus, rats younger than P23 display FPS. Specifically, high illumination levels were found to enhance startle amplitudes in rats aged 18 and 25 days, but not 14 days. Furthermore, the light-enhanced startle observed in P18 rats was prevented by a systemic injection of the noradrenergic beta-receptor antagonist propranolol. These data suggest that conditioned and unconditioned FPS have different ontogenetic trajectories, and thereby provide support for the idea that learned and unlearned fear are subserved by dissociable neural systems.