Location: Boston, Massachusetts2011 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. A contributing molecular factor to the disruption of cognitive performance may be macroautophagy. Autophagy, non-apoptotic cell death due to the accumulation of toxic proteins, is a well-regulated lysosomal process by which intracellular damaged toxic structures, such as protein/lipid complexes, protein oligomers/aggregates and cellular organelles, are identified, sequestered and/or recycled. Aging is characterized by progressive deterioration of cells and organs due to accumulation of damaged macromolecules and organelles. Therefore, continuous removal of worn-out components and replacement with newly synthesized ones ensures cellular homeostasis and delays the aging process. This year we measured autophagy in the hippocampus of rats exposed to radiation. Results showed an increased accumulation of p62/SQSTM1, an ubiquitin binding sequestering protein. This suggests an increase in ubiquitin-like inclusion bodies, resulting in low turnover or clearance for the lysosomal degradation. These results indicate an effect of exposure to HZE particles on autophagy and suggest a deficit in the capacity of cells to remove toxic proteins. We submitted a manuscript detailing these results this year. In a subsequent study we fed the rats diets containing either 2% blueberry or 2% strawberry to see if we could prevent the radiation-induced decreases in autophagy. This research is ongoing as we are currently running these studies and analyzing the data.