Location: Boston, Massachusetts2010 Annual Report
1a. Objectives (from AD-416)
1: Determine the effects of the radiation on several cognitive and motor behaviors (e.g., Morris water maze), and in addition examine additional new ones (e.g., elevated + maze). 2: Determine whether pre-feeding with Blueberry (BB) or Strawberry (SB) at 2-4% of the diet will prevent the radiation induced deficits in these parameters. 3: We will utilize several techniques (see approach) to assess the changes in several markers of phosphorylation that are important in cell signaling and neurogenesis.
1b. Approach (from AD-416)
The effects of Strawberry (SB) and/or Blueberry (BB) dietary supplementations (8 wks)(control, 2% BB, 2% SB or 1% each SB/BB extracts in the diet for 8 weeks) will be examined in non-irradiated or irradiated (4 mo Sprague Dawley) rats using cognitive and motor tasks. The tests utilized will be age-sensitive motor (inclined screen) and cognitive behaviors (Morris water maze performance, elevated plus maze, sensorimotor gating). We will then determine the effects of the supplementations on neuronal signaling and correlate these with alterations in behavioral parameters determined. We will utilize several techniques (e.g., Western blot analyses and immunocytochemistry) to assess the changes in several markers of phosphorylation that are important in cell communication and neurogenesis (e.g., calcium-dependent protein kinase C, PKC; extracellular signal regulated kinases, ERK).
3. Progress Report
Previous work has shown that exposure to heavy particle irradiation produces neurochemical and cognitive deficits in young animals that are characteristic of much older animals. As a result, it has been suggested that exposure to heavy particles can produce “accelerated aging.” Over the last several years of this project in collaboration with a scientist from UMBC, we have primarily examined the effects of 56Fe irradiation. Both aged and irradiated rats display cognitive impairment in tests of spatial learning and memory such as the Morris water maze and the radial arm maze. Therefore, in the present study, we used a combination of these two tests, the 8 arm radial water maze (RAWM), to measure spatial learning in rats which were irradiated with different doses of 56Fe radiation. Results showed that the irradiated rats had more reference and working memory errors while learning the maze, particularly on Day 3 of testing. Additionally, they utilized non-spatial strategies to solve the RAWM task whereas the control animals used spatial strategies. These results show that irradiation with 56Fe high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere. Ionizing radiation also increases inflammatory stress signaling. These increases in stress signals can repress autophagy, a dynamic process for intracellular degradation and recycling of toxic proteins as well as aging organelles in the brain. Therefore, we assessed the effects of 56Fe irradiation on autophagy functions in the brain. Preliminary results indicate that exposure to HZE may decrease autophagy, in rat brain such that the SN dopaminergic neurons of the 2.5 Gy exposure rats exhibited a substantial accumulation of ubiquitin bodies, an early indicator of a dysfunctional autophagic process, that was not seen in control rats. We are now carrying out studies to determine if there are radiation-induced alterations in additional markers of autophagy. Monitoring of this project is accomplished through e-mail and/or teleconference.