Long-Term Cognitive Functioning in Single-Dose Total-Body Gamma-Irradiated Rhesus Monkeys (Macaca mulatta)

Abstract

In this study, the effects of a potentially lethal radiation exposure on the brain for long-term cognitive sequelae were investigated using Rhesus macaques (Macaca mulatta) adopted from other facilities after analysis of acute radiation response via the Centers for Medical Countermeasures against Radiation (CMCR) network. Fifty-nine animals were given the opportunity to participate in cognitive cage-side testing. The animals that received single-dose gamma irradiation were significantly less likely to engage in cognitive testing than the controls, suggesting that irradiated animals may have differences in cognitive ability. Five irradiated (6.75–8.05 Gy) and three naïve control animals self-selected, were extensively trained and administered a simple visual discrimination with reversal (SVD+R) task 2–3 times per week for 11–18 months. Each session consisted of 30 trials in which the animals were required to choose the correct visual stimulus for a food reward. After the initial presentation, the stimulus that signaled the presence of food was twice reversed once the animal reached criterion (90% accuracy across four consecutive sessions). While the limited sample size precluded definitive statistical analysis, irradiated animals took longer to reach the criterion subsequent to reversal than did control animals, suggesting a relative deficiency in cognitive flexibility. These results provide preliminary data supporting the potential use of a nonhuman primate model to study radiation-induced, late-delayed cognitive deficits.

Nonhuman primates as models for the discovery and development of radiation countermeasures

“…At 9 months post-irradiation cognitive tasks was markedly reduced compared to pre-irradiation values [41]. Another study examined the effects of long-term cognitive functioning in rhesus macaques exposed to single TBI (6.75–8.05 Gy) and tested using simple visual discrimination with reversal tasks [42]. Irradiated animals were significantly less likely to engage in at least one task than age-matched, non-irradiated controls.…”

Solving the Issue of Ionizing Radiation Induced Neurotoxicity by Using Novel Cell Models and State of the Art Accelerator Facilities

“…In rodents, the radiation-induced loss of glial oligodendrocyte progenitor cells followed by demyelination of neurons ends up with white matter necrosis [59], which is also seen in humans [70]. These impacts on mammalian brains may contribute to impairments in behavior and to memory deficits as assessed by the Barnes maze [55,60] and visual discrimination tests [54] and may also mirror cognitive defects seen in humans.…”

Sex-Specific Effects of a Wartime-Like Radiation Exposure on Cognitive Function

“…Those irradiated animals were less likely to engage in behavior testing, suggested to be a result of attention deficits. Otherwise, the irradiated NHP were slower to learn and complete the task, and had reduced cognitive flexibility (45). Furthermore, these animals exhibited evidence of persistent inflammation, expression of complement proteins and T-cell activation, as well as impaired glutamatergic neurotransmission and signal transduction within the white matter of the brain (46).…”