Submitted to: Radiation Research
Publication Type: Peer reviewed journal
Publication Acceptance Date: 8/6/2002
Publication Date: 12/1/2002
Citation: DENISOVA, N.A., SHUKITT HALE, B., RABIN, B., JOSEPH, J.A. BRAIN SIGNALING AND BEHAVIORAL RESPONSES INDUCED BY EXPOSURE TO 56FE RADIATION. RADIATION RESEARCH. 2002.158(6):725-34. Interpretive Summary: Previous research suggests that young rats exposed to irradiation develop significant behavioral (i.e., memory) deficits. In this regard it has been theorized that astronauts on long-term space flights might experience similar memory deficits induced by irradiation. We investigated the effect of irradiation on brain activity. Our results confirm our previous findings and demonstrate that irradiated rats develop significant behavioral (memory) deficits. The behavioral abnormalities were associated with deficits in brain cellular communication. Specifically, brain cellular communication and brain activity were significantly lower in irradiated rats compared to non irradiated rats. Although our results suggest that antioxidants (e.g., vitamin E, etc.) will not have beneficial effects against irradiation it is important to develop interventions that will prevent irradiation-induced damage to brain and subsequent behavior activities.
Technical Abstract: Similar to adverse behavioral and neuronal effects seen in aged animals, exposing rats to 1.5 Gy (1 GeV) 56Fe produced age-like accelerations in behavioral deficits by disrupting the dopaminergic (DA)system integrity. However, molecular mechanisms involved in these deficits are not known. In this regard it is known that astronauts on long-term space flights will be exposed to similar heavy particle irradiation that might have similar deleterious effects on neuronal signaling and cognitive behavior. Thus, present study evaluated whether irradiation-induced behavioral deficit (reference and working memory errors) is associated with increased brain-region-specific vulnerability to oxidative stress and facilitation of synaptic plasticity [pre-synaptic vesicle proteins and protein kinases (PK)]. These signaling molecules were previously found to be essential for behavior, and they were assessed in striatum, hippocampus, and frontal cortex. Results demonstrated a significant irradiation-induced increase in reference memory errors. The increases in reference memory errors were significantly negatively correlated with striatal synaptobrevin (SBRV), while both types of errors were significantly negatively correlated with frontal cortical synaptophysin (SPHY) expression. Both SPHY and SBRV are synaptic vesicle proteins important in cognition. Moreover, striatal PKA, a memory signaling molecule was also significantly negatively correlated with reference memory errors. Overall, our findings suggest that irradiation-induced pre-synaptic facilitation, particularly in striatum, may be responsible for the previously reported irradiation-induced decrease in DA release and for the disruption of the central DA system integrity and DA-mediated behavior. Moreover, our findings suggest that oxidative stress is not a major factor in the irradiation-induced behavioral deficits.