Abstract
The present report describes an animal model for examining the effects of radiation on a range of neurocognitive functions in rodents that are similar to a number of basic human cognitive functions. Fourteen male Long-Evans rats were trained to perform an automated intra-dimensional set shifting task that consisted of their learning a basic discrimination between two stimulus shapes followed by more complex discrimination stages (e.g., a discrimination reversal, a compound discrimination, a compound reversal, a new shape discrimination, and an intra-dimensional stimulus discrimination reversal). One group of rats was exposed to head-only X-ray radiation (2.3 Gy at a dose rate of 1.9 Gy/min), while a second group received a sham-radiation exposure using the same anesthesia protocol. The irradiated group responded less, had elevated numbers of omitted trials, increased errors, and greater response latencies compared to the sham-irradiated control group. Additionally, social odor recognition memory was tested after radiation exposure by assessing the degree to which rats explored wooden beads impregnated with either their own odors or with the odors of novel, unfamiliar rats; however, no significant effects of radiation on social odor recognition memory were observed. These data suggest that rodent tasks assessing higher-level human cognitive domains are useful in examining the effects of radiation on the CNS, and may be applicable in approximating CNS risks from radiation exposure in clinical populations receiving whole brain irradiation.
Highlights
Radiation therapy is a common treatment for numerous cancers in children and adults but it has deleterious effects on healthy tissue
When collapsed across Radiation, all rats committed more errors on SDRev compared to simple discrimination (SD) (p = 0.018), but errors were similar on CD reversal (CDRev) relative to compound discrimination (CD) (p = 0.461) and on IDS reversal discrimination (IDSRev) relative to intra-dimensional shift (IDS) (p = 0.537)
The present results show that 2.3 Gy of head-only X-irradiation produces deficits in performance on complex visual discriminations, but no significant deficits on social recognition memory
Summary
Radiation therapy is a common treatment for numerous cancers in children and adults but it has deleterious effects on healthy tissue. Radiation-induced cognitive deficits are reported in 50– 90% of adult patients receiving therapeutic whole brain irradiations surviving for 6 months or more post-exposure [1]. Numerous preclinical investigations have supported the sensitivity of the hippocampus to radiation-induced damage, given the fact that radiation decreases hippocampal neurogenesis and induces hippocampal-dependent cognitive deficits in rodents [2]. While patients report cognitive deficits associated with both hippocampus- and non-hippocampus-dependent cognitive domains, there is a lack of preclinical data examining the effects of radiation on behaviors mediated by brain regions other than the hippocampus. There is a need for research focused on tasks related to the function of other brain structures in rodents, in order to further understand radiation’s effects on these other complex cognitive domains reported to be negatively effected by therapeutic radiation in humans
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