Neurobehavioral effects of acute low-dose whole-body irradiation.

Radiation exposure has multiple effects on the brain, behavior and cognitive functions. It has been reported that high-dose (>20 Gy) radiation-induced behavior and cognitive aberration partly associated with severe tissue destruction. Low-dose (<3 Gy) exposure can occur in radiological disasters and cerebral endovascular treatment. However, only a few reports analyzed behavior and cognitive functions after low-dose irradiation. This study was undertaken to assess the relationship between brain neurochemistry and behavioral disruption in irradiated mice. The irradiated mice (0.5 Gy, 1 Gy and 3 Gy) were tested for alteration in their normal behavior over 10 days. A serotonin (5-HT), Dopamine, gamma-Aminobutyric acid (GABA) and cortisol analysis was carried out in blood, hippocampus, amygdala and whole brain tissue. There was a significant decline in the exploratory activity of mice exposed to 3 Gy and 1 Gy radiation in an open field test. We observed a significant short-term memory loss in 3 Gy and 1 Gy irradiated mice in Y-Maze. Mice exposed to 1 Gy and 3 Gy radiation exhibited increased anxiety in an elevated plus maze (EPM). The increased anxiety and memory loss patterns were also seen in 0.5 Gy irradiated mice, but the results were not statistically significant. In this study we observed that neurotransmitters are significantly altered after irradiation, but the neuronal cells in the hippocampus were not significantly affected. This study suggests that the low-dose radiation-induced cognitive impairment may be associated with the neurochemical in low-dose irradiation and unlike the high-dose scenario might not be directly related to the morphological changes in the brain.

Delayed effects of a single-dose whole-brain radiation therapy on glucose metabolism and myelin density: a longitudinal PET study.

PURPOSE: Radiotherapy is an important treatment option for brain tumors, but the unavoidable irradiation of normal brain tissue can lead to delayed cognitive impairment. The mechanisms involved are still not well explained and, therefore, new tools to investigate the processes leading to the delayed symptoms of brain irradiation are warranted. In this study, positron emission tomography (PET) is used to explore delayed functional changes induced by brain irradiation. MATERIALS AND METHODS: Male Wistar rats were subjected to a single 25-Gy dose of whole brain X-ray irradiation, or sham-irradiation. To investigate delayed effects of radiation on cerebral glucose metabolism and myelin density, 18F-fluorodeoxyglucose (18F-FDG) PET scans were performed at baseline and on day 64 and 94, whereas N-11C-methyl-4,4'-diaminostilbene (11C-MeDAS) PET scans were performed at baseline and on day 60 and 90 post-irradiation. In addition, the open field test (OFT) and novel spatial recognition (NSR) test were performed at baseline and on days 59 and 89 to investigate whether whole brain irradiation induces behavioral changes. RESULTS: Whole-brain irradiation caused loss of bodyweight and delayed cerebral hypometabolism, with 18F-FDG uptake in all brain regions being significantly decreased in irradiated rat on day 64 while it remained unchanged in control animals. Only amygdala and cortical brain regions of irradiated rats still showed reduced 18F-FDG uptake on day 94. 11C-MeDAS uptake in control animals was significantly lower on days 60 and 90 than at the baseline, suggesting a reduction in myelin density in young adults. In irradiated animals, 11C-MeDAS uptake was similarly reduced on day 60, but on day 90 tracer uptake was somewhat increased and not significantly different from baseline anymore. Behavioral tests showed a similar pattern in control and irradiated animals. In both groups, the OFT showed significantly reduced mobility on days 59 and 89, whereas the NSR did not reveal any significant changes in spatial memory over time. Interestingly, a positive correlation between the NSR and 11C-MeDAS uptake was observed in irradiated rats. CONCLUSIONS: Whole-brain irradiation causes delayed brain hypometabolism, which is not accompanied by white matter loss. Irradiated animals showed similar behavioral changes over time as control animals and, therefore, cerebral hypometabolism could not be linked to behavioral abnormalities. However, spatial memory seems to be associated with myelin density in irradiated rats.

Egocentric and allocentric representations in auditory cortex.

A key function of the brain is to provide a stable representation of an object's location in the world. In hearing, sound azimuth and elevation are encoded by neurons throughout the auditory system, and auditory cortex is necessary for sound localization. However, the coordinate frame in which neurons represent sound space remains undefined: classical spatial receptive fields in head-fixed subjects can be explained either by sensitivity to sound source location relative to the head (egocentric) or relative to the world (allocentric encoding). This coordinate frame ambiguity can be resolved by studying freely moving subjects; here we recorded spatial receptive fields in the auditory cortex of freely moving ferrets. We found that most spatially tuned neurons represented sound source location relative to the head across changes in head position and direction. In addition, we also recorded a small number of neurons in which sound location was represented in a world-centered coordinate frame. We used measurements of spatial tuning across changes in head position and direction to explore the influence of sound source distance and speed of head movement on auditory cortical activity and spatial tuning. Modulation depth of spatial tuning increased with distance for egocentric but not allocentric units, whereas, for both populations, modulation was stronger at faster movement speeds. Our findings suggest that early auditory cortex primarily represents sound source location relative to ourselves but that a minority of cells can represent sound location in the world independent of our own position.

Possible cause for altered spatial cognition of prepubescent rats exposed to chronic radiofrequency electromagnetic radiation.

The effects of chronic and repeated radiofrequency electromagnetic radiation (RFEMR) exposure on spatial cognition and hippocampal architecture were investigated in prepubescent rats. Four weeks old male Wistar rats were exposed to RF-EMR (900 MHz; SAR-1.15 W/kg with peak power density of 146.60 µW/cm(2)) for 1 h/day, for 28 days. Followed by this, spatial cognition was evaluated by Morris water maze test. To evaluate the hippocampal morphology; H&E staining, cresyl violet staining, and Golgi-Cox staining were performed on hippocampal sections. CA3 pyramidal neuron morphology and surviving neuron count (in CA3 region) were studied using H&E and cresyl violet stained sections. Dendritic arborization pattern of CA3 pyramidal neuron was investigated by concentric circle method. Progressive learning abilities were found to be decreased in RF-EMR exposed rats. Memory retention test performed 24 h after the last training revealed minor spatial memory deficit in RF-EMR exposed group. However, RF-EMR exposed rats exhibited poor spatial memory retention when tested 48 h after the final trial. Hirano bodies and Granulovacuolar bodies were absent in the CA3 pyramidal neurons of different groups studied. Nevertheless, RF-EMR exposure affected the viable cell count in dorsal hippocampal CA3 region. RF-EMR exposure influenced dendritic arborization pattern of both apical and basal dendritic trees in RF-EMR exposed rats. Structural changes found in the hippocampus of RF-EMR exposed rats could be one of the possible reasons for altered cognition.

Spatial updating of map-acquired representation.

In the present study, we examined whether people can update a map-acquired spatial representation. The participants learned a spatial layout from a map displayed on a computer screen, and then performed spatial judgments at a novel position either in the same room (Exp. 1) or in a distal room (Exp. 2). They were required to imagine the spatial layout from a perspective aligned with the learning direction, aligned with their facing direction during testing, or toward a novel direction misaligned with the two directions mentioned above. In both the immediate and nonimmediate environments, the participants performed better from the learning direction than from the novel direction, and also performed better from the facing direction than from the novel direction. These results reveal that people establish an orientation-specific spatial representation through map learning, and that they can update a map-acquired representation during locomotion.

Early-delayed, radiation-induced cognitive deficits in adult rats are heterogeneous and age-dependent.

Patients treated with whole-brain irradiation often develop cognitive deficits that are presumed to result from normal tissue injury. Age is a risk factor for these side effects. We compared the cognitive effects of fractionated whole-brain irradiation (300 kV X rays) in rats irradiated either as young adults or in middle age. A deficit in object memory was apparent at 3 months in rats irradiated as young adults, however, no comparable deficit was apparent in rats irradiated in middle age. In addition, the deficit in object memory in young adults was no longer apparent at 6 and 12 months after fractionated whole-brain irradiation and no radiation-induced deficit was detectable in a spatial memory task at any time, regardless of age at time of irradiation. Thus, clinically relevant fractionated whole-brain irradiation in adult rats resulted in early-delayed cognitive changes that were heterogeneous, transient and age-dependent. The results of the current and previous studies of radiation-induced cognitive changes support the continued investigation and validation of rodent models of radiation-induced brain injury, which are critical for developing and testing new therapies for treatment-induced cognitive dysfunction in cancer survivors.

Celestial orientation with the sun not in view: lizards use a time-compensated sky polarization compass.

The present investigation was aimed at testing whether the lizard sky polarization compass is time compensated. For this purpose, ruin lizards, Podarcis sicula, were both trained and tested for orientation inside a Morris water maze under clear skies with the sun not in view. During training, lizards showed a striking bimodal orientation along the training axis, demonstrating their capability of determining the symmetry plane of the sky polarization pattern and thus the use of polarization information in orientation. After reaching criteria, lizards were kept 7 days in a 6-h fast clock-shift treatment and then released with the sun not in view. Six-hour clock-shifted lizards showed a bimodal distribution of directional choices, which was oriented perpendicularly to the training axis, as it was expected on the basis of the clock-shift. The results show that the only celestial diurnal compass mechanism that does not need a direct vision of the sun disk (i.e., the sky polarization compass) is a time-compensated compass.

Comparison of the effects of partial- or whole-body exposures to ¹6O particles on cognitive performance in rats.

Studies using a ground-based system (NASA Space Radiation Laboratory) to examine the effects of exposure to high-energy charged particles or HZE particles on cognitive performance have interchangeably used whole-body exposures or exposures restricted to the head of the subject. For this study, we hypothesized that different types of exposure such as whole body vs. head only vs. body only might modulate the impact of irradiation on cognitive performance in different ways with the resulting cognitive performance outcomes being either independent of exposure type or strongly dependent on exposure type with each producing performance outcomes. To test these possibilities, three groups of rats were exposed to ¹6O particles (1,000 MeV/n): (1) head only; (2) body only; (3) whole body. Cognitive performance was measured using the elevated plus-maze, novel object recognition, spatial location memory and operant responding on an ascending fixed-ratio schedule. The results indicated that the performance of the rats on the spatial location memory task was markedly different when they received head-only irradiation compared to whole-body exposure. For the operant responding task, irradiation of the whole body resulted in a more severe performance decrement than exposures restricted to the head. The results are discussed in terms of nontargeted effects of HZE particles and the findings suggest that studies that utilize different patterns of exposure may not be directly comparable and that astronauts may be at a greater risk for HZE particle-induced cognitive deficits than previously thought.

[Galactic heavy charged particles damaging effect on biological structures].

A concept of the radiation risk of the manned interplanetary flights is proposed and substantiated. Heavy charged particles that are a component of the galactic cosmic rays (GCR) have a high damaging effect on the biological structures as great amount of energy is deposited in heavy particle tracks. The high biological effectiveness of heavy ions is observed in their action on cell genetic structures and the whole organism, including the brain structures. The hippocampus is the part of the central nervous system that is the most sensitive to radiation--first of all, to heavy charged particles. Irradiation of animals with accelerated iron ions at doses corresponding to the real fluxes of GCR heavy nuclei, to which Mars mission crews can be exposed, leads to marked behavioral function disorders in the post-irradiation period. To evaluate the radiation risk for the interplanetary flight crews, the concept of successful mission accomplishment is introduced. In these conditions, the central nervous system structures can be the critical target of GCR heavy nuclei. Their damage can modify the higher integrative functions of the brain and cause disorders in the crew members' operator performances.

Effects of prenatal irradiation on behaviour and hippocampal neurogenesis in adult rats.

Prenatal irradiation is known to have aversive effects on the brain development, manifested in changes in some behavioural parameters in adult individuals. The aim of our work was to assess the effect of prenatal irradiation on different forms of behaviour and on hippocampal neurogenesis in rats. Pregnant female rats were irradiated with a dose of 1 Gy of gamma rays on the 16th day of gravidity. The progeny of irradiated and control animals aged 3 months were tested in Morris water maze (MWM), open field (OF) and in elevated plus maze test (PM). The prenatal irradiation negatively influenced the short-term spatial memory in MWM in female rats, although the long-term memory was not impaired. A statistically significant increase of basic locomotor activity in OF was observed in irradiated rats. The comfort behaviour was not altered. The results of PM showed an increase of anxiety in irradiated females. The level of hippocampal neurogenesis, assessed as the number of cells labelled with 5-bromo-2-deoxyuridine in the area of gyrus dentatus, was not statistically different in irradiated rats. Our results indicate, that prenatal irradiation with a low dose of gamma-rays can affect some innate and learned forms of behaviour in adult rats. We did not confirm a relation of behavioural changes to the changes of hippocampal neurogenesis.

The polyamine inhibitor alpha-difluoromethylornithine modulates hippocampus-dependent function after single and combined injuries.

Exposure to uncontrolled irradiation in a radiologic terrorism scenario, a natural disaster or a nuclear battlefield, will likely be concomitantly superimposed on other types of injury, such as trauma. In the central nervous system, radiation combined injury (RCI) involving irradiation and traumatic brain injury may have a multifaceted character. This may entail cellular and molecular changes that are associated with cognitive performance, including changes in neurogenesis and the expression of the plasticity-related immediate early gene Arc. Because traumatic stimuli initiate a characteristic early increase in polyamine metabolism, we hypothesized that treatment with the polyamine inhibitor alpha-difluoromethylornithine (DFMO) would reduce the adverse effects of single or combined injury on hippocampus structure and function. Hippocampal dependent cognitive impairments were quantified with the Morris water maze and showed that DFMO effectively reversed cognitive impairments after all injuries, particularly traumatic brain injury. Similar results were seen with respect to the expression of Arc protein, but not neurogenesis. Given that polyamines have been found to modulate inflammatory responses in the brain we also assessed the numbers of total and newly born activated microglia, and found reduced numbers of newly born cells. While the mechanisms responsible for the improvement in cognition after DFMO treatment are not yet clear, the present study provides new and compelling data regarding the potential use of DFMO as a potential countermeasure against the adverse effects of single or combined injury.

Ultraviolet polarization vision and visually guided behavior in fishes.

Teleost fishes are capable of detecting and behaviorally responding to linearly polarized light. Fish exhibit free-swimming spatial orientation to imposed and natural polarized light fields, and the fidelity of this spatial orientation depends heavily on UV and short wavelength content of the polarization field. Fish make fine-scale behavioral discriminations between stimuli that differ in e-vector orientation, independent of brightness. The detection of polarized light by photoreceptors is based on specializations of the disk membrane in the outer segment of cones that permit preferential absorption of axial and transverse polarized light. Differential polarization detectors that have overlapping spectral sensitivity in the UV short wavelength spectrum mediate polarization sensitivity. These differential detectors are based on cone photoreceptors that share spectral sensitivity in the UV short wavelength spectrum: the alpha-band of UV-sensitive cone mechanism as the vertical detector, and the beta-band of mid- and long-wavelength sensitive cone mechanisms as the horizontal detector. Negative feedback of horizontal cells on cones govern opponent interactions between differentially sensitive polarization detectors. Polarization opponency functions to enhance e-vector contrast under conditions that vary in degree of polarization and ambient intensity. Ontogenetic changes in the cone mosaic, resulting from programmed cell death and regeneration of UV-sensitive cones, alter the retinal location of polarization sensitivity. These developmental changes greatly influence behavioral responses to polarized light.

Decoding movement trajectories through a T-maze using point process filters applied to place field data from rat hippocampal region CA1.

Firing activity from neural ensembles in rat hippocampus has been previously used to determine an animal's position in an open environment and separately to predict future behavioral decisions. However, a unified statistical procedure to combine information about position and behavior in environments with complex topological features from ensemble hippocampal activity has yet to be described. Here we present a two-stage computational framework that uses point process filters to simultaneously estimate the animal's location and predict future behavior from ensemble neural spiking activity. First, in the encoding stage, we linearized a two-dimensional T-maze, and used spline-based generalized linear models to characterize the place-field structure of different neurons. All of these neurons displayed highly specific position-dependent firing, which frequently had several peaks at multiple locations along the maze. When the rat was at the stem of the T-maze, the firing activity of several of these neurons also varied significantly as a function of the direction it would turn at the decision point, as detected by ANOVA. Second, in the decoding stage, we developed a state-space model for the animal's movement along a T-maze and used point process filters to accurately reconstruct both the location of the animal and the probability of the next decision. The filter yielded exact full posterior densities that were highly nongaussian and often multimodal. Our computational framework provides a reliable approach for characterizing and extracting information from ensembles of neurons with spatially specific context or task-dependent firing activity.

Spatial memory performance of Wistar rats exposed to mobile phone.

INTRODUCTION: With the tremendous increase in number of mobile phone users world wide, the possible risks of this technology have become a serious concern. OBJECTIVE: We tested the effects of mobile phone exposure on spatial memory performance. MATERIALS AND METHODS: Male Wistar rats (10-12 weeks old) were exposed to 50 missed calls/day for 4 weeks from a GSM (900/1800 MHz) mobile phone in vibratory mode (no ring tone). After the experimental period, the animals were tested for spatial memory performance using the Morris water maze test. RESULTS: Both phone exposed and control animals showed a significant decrease in escape time with training. Phone exposed animals had significantly (approximately 3 times) higher mean latency to reach the target quadrant and spent significantly (approximately 2 times) less time in the target quadrant than age- and sex-matched controls. CONCLUSION: Mobile phone exposure affected the acquisition of learned responses in Wistar rats. This in turn points to the poor spatial navigation and the object place configurations of the phone-exposed animals.

Spatial memory perfomance of wistar rats exposed to mobile phone

INTRODUCTION: With the tremendous increase in number of mobile phone users world wide, the possible risks of this technology have become a serious concern. OBJECTIVE: We tested the effects of mobile phone exposure on spatial memory performance. MATERIALS AND METHODS: Male Wistar rats (10-12 weeks old) were exposed to 50 missed calls/day for 4 weeks from a GSM (900/1800MHz) mobile phone in vibratory mode (no ring tone). After the experimental period, the animals were tested for spatial memory performance using the Morris water maze test. RESULTS: Both phone exposed and control animals showed a significant decrease in escape time with training. Phone exposed animals had significantly (~3 times) higher mean latency to reach the target quadrant and spent significantly (~2 times) less time in the target quadrant than age- and sex-matched controls. CONCLUSION: Mobile phone exposure affected the acquisition of learned responses in Wistar rats. This in turn points to the poor spatial navigation and the object place configurations of the phone-exposed animals.

Chronic exposure to low-intensity magnetic field improves acquisition and maintenance of memory.

Although past research has suggested that acute exposure to extremely low-frequency magnetic field (ELF MF) impairs learning and memory function, data on chronic exposure remain scarce. In this study, we examined the changes in spatial learning and memory by the Morris water maze test after 4 weeks of daily exposure of rats to a 50-Hz magnetic field of 2 mT for either 1 or 4 h. We found that chronic exposure to ELF MF reduced the latency to find the hidden platform and improved long-term memory of former location of platform without affecting the short-term memory and motor activity. These findings for the first time indicate that chronic exposure to ELF MF exerts a positive effect on the acquisition and maintenance of spatial memory.

Repeated application of an electric field increases BDNF in the brain, enhances spatial learning, and induces infarct tolerance.

Development of a safe method to increase brain-derived neurotrophic factor (BDNF) in the brain is expected to have utility in enhancing learning and memory, in protecting the brain, and in suppressing appetite. We investigated the effects of whole-body exposure to high voltage electric potential (HELP), which generates an electric field and current density in the body, on BDNF levels in the brain, spatial learning, or resistance to cerebral infarction development after focal ischemia. Adult mice (C57BL/6J) were exposed to 3.5 kV, or 5.8 kV for 5 h a day, making indirect contact with the ground via room air, over 1, 3, 6 or 12 consecutive weeks. After treatment, BDNF levels, performances in the Morris water maze task (MWM), or development of infarct lesion after focal ischemia was analyzed. Treatment with 3.5 kV for 1, 3, 6 or 12 weeks, or with 5.8 kV for 1, 3 or 12 weeks increased BDNF levels in the cortex (P<0.05, one-way ANOVA). Every HELP treatment differentially improved escape latency in the MWM, compared with the corresponding untreated controls (P<0.05, one-way ANOVA). Treatment with 3.5 kV for 6 or 12 weeks, but not with 5.8 kV protected the brain suppressing cerebral infarction development (P<0.05). The HELP treatment with 3.5 kV for 6 or 12 weeks improves spatial learning, gently suppressing body weight gain, and protects the brain against cerebral infarction.

Long-term exposure to extremely low-frequency magnetic fields impairs spatial recognition memory in mice.

1. In the present study, we investigated the short- and long-term effects of extremely low-frequency (ELF) magnetic fields on spatial recognition memory in mice by using a two-trial recognition Y-maze that is based on the innate tendency of rodents to explore novel environments. 2. Mice were exposed to 25 or 50 Hz electromagnetic fields for either 7 (short term) or 25 days (long term) and then tested in the Y-maze. 3. The results indicated that neither short- nor long-term exposure to magnetic fields affected the locomotor activity of mice in the Y-maze. However, long-term exposure to 50 Hz fields reduced recognition of the novel arm. 4. Our findings suggest that ELF magnetic fields impair spatial recognition memory in the Y-maze depending on the field strength and/or duration of exposure.

Ablation of antennae does not disrupt magnetoreceptive behavioural reaction of the American cockroach to periodically rotated geomagnetic field.

Neither a mode of function nor an exact anatomical localisation of the animal magnetoreceptor have been identified in any organism. Insects' antennae are organs specialized as unique neural input structures for a number of sensory modalities and have also been suggested to play a certain role in magnetoreception. In the present study, we used the American cockroach Periplaneta americana and tested the impact of amputation of both its antennae on the spontaneous magnetosensitive behaviour. By means of a full-laboratory assay we registered a non-specific unlearned movement reaction to the changing magnetic environment within the frame of the natural time and intensity parameters of the field. We report no loss of the magnetoreceptive behaviour in antennaeless cockroaches. Our finding narrows the spectrum of the insects' magnetite-rich nerve structures which might potentially be involved in magnetoreception.

Polarized skylight navigation in insects: model and electrophysiology of e-vector coding by neurons in the central complex.

Many insects exploit skylight polarization for visual compass orientation or course control. As found in crickets, the peripheral visual system (optic lobe) contains three types of polarization-sensitive neurons (POL neurons), which are tuned to different ( approximately 60 degrees diverging) e-vector orientations. Thus each e-vector orientation elicits a specific combination of activities among the POL neurons coding any e-vector orientation by just three neural signals. In this study, we hypothesize that in the presumed orientation center of the brain (central complex) e-vector orientation is population-coded by a set of "compass neurons." Using computer modeling, we present a neural network model transforming the signal triplet provided by the POL neurons to compass neuron activities coding e-vector orientation by a population code. Using intracellular electrophysiology and cell marking, we present evidence that neurons with the response profile of the presumed compass neurons do indeed exist in the insect brain: each of these compass neuron-like (CNL) cells is activated by a specific e-vector orientation only and otherwise remains silent. Morphologically, CNL cells are tangential neurons extending from the lateral accessory lobe to the lower division of the central body. Surpassing the modeled compass neurons in performance, CNL cells are insensitive to the degree of polarization of the stimulus between 99% and at least down to 18% polarization and thus largely disregard variations of skylight polarization due to changing solar elevations or atmospheric conditions. This suggests that the polarization vision system includes a gain control circuit keeping the output activity at a constant level.