Early Effects of Whole-Body⁵⁶Fe Irradiation on Hippocampal Function in C57BL/6J Mice

Abstract

Relatively little is known about early irradiation effects on hippocampal function in wild-type mice. In this study, the effects of 56Fe irradiation on hippocampal function were assessed starting 2 weeks after whole-body irradiation. Compared to sham irradiation, radiation impaired novel object recognition in female and male C57BL/6J wild-type mice. There were no effects of irradiation on contextual fear conditioning or spatial memory retention in the water maze. It is possible that oxidative damage might contribute to radiation-induced cognitive changes. Therefore, hippocampal and cortical levels of 3-nitrotyrosine (3NT) and lipid peroxidation, measures of oxidative damage were assessed. There were no effects of irradiation on these measures of oxidative damage. As 56Fe irradiation can increase reactive oxygen species (ROS) levels, which may contribute to the impairments in novel object recognition, the effects of the antioxidant alpha-lipoic acid (ALA) on cognition following sham irradiation and irradiation were also assessed. ALA did not prevent radiation-induced impairments in novel object recognition and impaired spatial memory retention of sham-irradiated and irradiated mice in the probe trial after the first day of hidden platform training in the water maze. Thus, the novel object recognition test is particularly sensitive to detect early cognitive effects of 56Fe irradiation through a mechanism unlikely involving ROS or oxidative damage.

Dose- and ApoE Isoform-Dependent Cognitive Injury after Cranial56Fe Irradiation in Female Mice

“…(2015) have extended the results of the NOR task and complementary novel location or object in place (OiP) test to very small doses of 600 MeV/n 16 O and 48 Ti particles using 6-month-old male transgenic mice [strain Tg(Thy1-EGFP) expressing the Thy1-EGFP transgene]. These animals were significantly older than those examined by Haley et al (2013) above. The data showed substantial impairment in NOR and OiP performance 6 weeks postirradiation after 5 -30-cGy exposures depending on ion type, as shown in Figure 10.…”

“…The age at evaluation and irradiation affects the responses to charged particles (Rabin et al 2012) and X-rays (Forbes et al 2014). Sex and genotype (e.g., ApoE allele and ATM) are important variables (Acevedo et al 2008;Benice and Raber 2009;Haley et al 2012;Higuchi et al 2002;Villasana et al 2006Villasana et al , 2011Yamamoto et al 2011;Yeiser et al 2013;Johnson et al 2014;Parihar et al 2014). Additionally, observations comparing head only-, body only-, or whole body-irradiated animals demonstrate a significant role for the periphery in determining behavioral responses .…”

“…Rodents normally spend more time exploring the novel object, and the proportion of time spent exploring the new object divided by the total object exploration time is used as the discrimination index. Haley et al (2013) studied the effects of 56 Fe particles on hippocampal function in male and female C57Bl/6J mice irradiated with 10 -50 cGy of 600 MeV/n 56 Fe ions and tested those 2 weeks later. Compared to sham irradiation, radiation impaired novel object recognition and spatial memory retention in female and male C57Bl/6J wild-type mice at an early time point at doses as low as 0.1 Gy.…”

Chronic methamphetamine exposure prior to middle cerebral artery occlusion increases infarct volume and worsens cognitive injury in Male mice

“…The particular novel object recognition paradigm used in this study involved a 24-hour period between training and testing and relies primarily on the hippocampus and entorhinal, perirhinal, and parahippocampal cortices (Baxter, 2010). Previous studies in our laboratory have indicated that this test is particularly sensitive in detecting cognitive injury following environmental challenges (Haley et al, 2013). On day 1 (habituation), 48 hours after tMCAO, mice were placed into an open field (16″ × 16″ Kinder Scientific, Poway, CA) for 15 minutes.…”

Impact of Breathing 100% Oxygen on Radiation-Induced Cognitive Impairment

“…Ground-based studies using air-breathing animals and simulated space radiations have reported radiation-induced brain injuries, including deleterious effects on dividing neuronal precursor cells in the hippocampus (1–3), nondividing hippocampal neurons (3, 4) and cognitive function (5–9). Recently published reviews suggest that acute radiation-induced oxidative stress and inflammation generate chronic reactive oxygen species that may ultimately result in late radiation-induced brain injury, including cognitive impairment (10–12).…”