Induction of fatigue-like behavior by pelvic irradiation of male mice alters cognitive behaviors and BDNF expression.

Fatigue and cognitive deficits are often co-occurring symptoms reported by patients after radiation therapy for prostate cancer. In this study, we induced fatigue-like behavior in mice using targeted pelvic irradiation to mimic the clinical treatment regimen and assess cognitive behavioral changes. We observed that pelvic irradiation produced a robust fatigue phenotype, a reduced rate of spontaneous alternation in a Y-maze test, and no behavioral change in an open field test. We found that reversal learning for fatigued mice was slower with respect to time, but not with respect to effort put into the test, suggesting that fatigue may impact the ability or motivation to work at a cognitive task without impairing cognitive capabilities. In addition, we found that mice undergoing pelvic irradiation show lower whole-brain levels of mature BDNF, and that whole-brain proBDNF levels also correlate with spontaneous alternation in a Y-maze test. These results suggest that changes in BDNF levels could be both a cause and an effect of fatigue-related changes in behavior.

Multi-domain cognitive assessment of male mice shows space radiation is not harmful to high-level cognition and actually improves pattern separation.

Astronauts on interplanetary missions - such as to Mars - will be exposed to space radiation, a spectrum of highly-charged, fast-moving particles that includes 56Fe and 28Si. Earth-based preclinical studies show space radiation decreases rodent performance in low- and some high-level cognitive tasks. Given astronaut use of touchscreen platforms during training and space flight and given the ability of rodent touchscreen tasks to assess functional integrity of brain circuits and multiple cognitive domains in a non-aversive way, here we exposed 6-month-old C57BL/6J male mice to whole-body space radiation and subsequently assessed them on a touchscreen battery. Relative to Sham treatment, 56Fe irradiation did not overtly change performance on tasks of visual discrimination, reversal learning, rule-based, or object-spatial paired associates learning, suggesting preserved functional integrity of supporting brain circuits. Surprisingly, 56Fe irradiation improved performance on a dentate gyrus-reliant pattern separation task; irradiated mice learned faster and were more accurate than controls. Improved pattern separation performance did not appear to be touchscreen-, radiation particle-, or neurogenesis-dependent, as 56Fe and 28Si irradiation led to faster context discrimination in a non-touchscreen task and 56Fe decreased new dentate gyrus neurons relative to Sham. These data urge revisitation of the broadly-held view that space radiation is detrimental to cognition.

Early postnatal x-irradiation of the hippocampus and discrimination learning in adult rats.

Rats with X-irradiation-produced degranulation of the hippocampal dentate gyrus were trained in the acquisition and reversal of simultaneous visual and tactile discriminations in a T-maze. These experiments employed the same treatment, apparatus, and procedure but varied in task difficulty. In the brightness and roughness discriminations, the irradiated rats were not handicapped in acquiring or reversing discriminations of low or low-moderate task difficulty. However, these rats were handicapped in acquiring and reversing discriminations of moderate and high task difficulty. In a Black/White discrimination, in which the stimuli were restricted to the goal-arm walls, the irradiated rats were handicapped in the acquisition (low task difficulty) and reversal (moderate task difficulty) phases of the task. These results suggest that the irradiated rats were not handicapped when the noticeability of the stimuli was high, irrespective of modality used, but were handicapped when the noticeability of the stimuli was low. In addition, these results are consistent with the hypothesis that rats with hippocampal damage are inattentive due to hyperactivity.

1439 MHz pulsed TDMA fields affect performance of rats in a T-maze task only when body temperature is elevated.

This study sought to clarify the effects of exposure to electromagnetic waves (EMW) used in cellular phones on learning and memory processes. Sprague-Dawley rats were exposed for either 1 h daily for 4 days or for 4 weeks to a pulsed 1439 MHz time division multiple access (TDMA) field in a carousel type exposure system. At the brain, average specific absorption rate (SAR) was 7.5 W/kg, and the whole body average SAR was 1.7 W/kg. Other subjects were exposed at the brain average SAR of 25 W/kg and the whole body average SAR of 5.7 W/kg for 45 min daily for 4 days. Learning and memory were evaluated by reversal learning in a food rewarded T-maze, in which rats learned the location of food (right or left) by using environmental cues. The animals exposed to EMW with the brain average SAR of 25 W/kg for 4 days showed statistically significant decreases in the transition in number of correct choices in the reversal task, compared to sham exposed or cage control animals. However, rats exposed to the brain average SAR of 7.5 W/kg for either 4 days or for 4 weeks showed no T-maze performance impairments. Intraperitoneal temperatures, as measured by a fiber optic thermometer, increased in the rats exposed to the brain average SAR of 25 W/kg but remained the same for the brain average SAR of 7.5 W/kg. The SAR of a standard cellular phone is restricted to a maximum of 2 W/kg averaged over 10 g tissue. These results suggest that the exposure to a TDMA field at levels about four times stronger than emitted by cellular phones does not affect the learning and memory processes when there are no thermal effects.

Teratology, survival, and reversal learning after fetal irradiation of mice by 2450-MHz microwave energy.

In the first of two factorially designed studies, 80 primigravid mice of the C3H-HeJ strain were subjected to 2450-MHz sinusoidally modulated microwave radiation or to sham radiation (with or without an accompanying injection of 5 mg of cortisone as a teratological marker) on the 11th, 12th, 13th or 14th day of gestation. The radiation treatment consisted of a single intense dosing of microwave energy (38 mW/g for 600 sec.= 22.8 J/g) in a multi-mode cavity. On the 19th day of gestation fetuses were taken via Caesarean section and were observed for gross structural abnormalities. While radiation of dams failed reliably to increase the incidence of fetal mortality or morbidity above that of controls, the dams treated with cortisone gave birth to reliably greater numbers of stillborn and deformed fetuses. In the second experiment and during their 14th day of gestation 60 primigravid mice received the radiation of sham-radiation treatment, half with, half without, the accompanying injection of cortisone. A virtually complete failure to survive to weaning characterized the pups born of the sham-radiated cortisone-treated group of dams, but the incidence of cortisone-induced mortality was reliably reduced in pups whose dams were also radiated by microwave energy. Pups sampled from all but the depleted group were observed later as young adults for competency in mastering a series of reversal habits in a water maze. No differences in maze performances were observed in the mice as a function of their placement in the control or the radiation condition, but offspring of cortisone-treated, radiated dams made reliably more errors. Careful measurement of elevations of colonic temperatures of radiated dams shortly after treatment with cortisone revealed an averaged deltaT that is close to that observed in a comparably radiated volume of water of equivalent mass. If the finding has generality beyond the gravid mouse-it, that is, cortisone effectively and reversibly renders the mammal ectothermic-an important advance in biological dosimetry of non-ionizing radiation may be at hand.