THE EFFECTS OF DOSE AND DURATION ON AGE-RELATED NEUROPROTECTION AND BEHAVIOR BY WILD BLUEBERRIES
Location: Human Nutrition Research Center on Aging
Project Number: 1950-51000-070-15
Start Date: Dec 31, 2009
End Date: Dec 31, 2012
To determine the dose and duration effects of the wild blueberry powder (WBP) on age-related differences in resistance to oxidative stress/inflammation (OS/INF) by exposing young and old animals to lipopolysaccharide (LPS). Brain regional differences in stress signaling (e.g,, nuclear factor kappa B, Nf'B), cytokine activation (e.g., TNFa), and OX-6, a marker of microglial activation, as well as differences in microglial morphology, will be assessed. Tissue levels of the polyphenols will be assessed following the various doses and durations of WBP to examine bioavailability.
AIM 1 - The effects of the age-related differences in resistance to inflammation will be assessed by supplementing (for 2, 4, or 8, weeks) young (4 mo) and old (19 mo) animals with a control diet or a diet containing the equivalent of 0, ½, or 1.5, 4.5 cups/day (in human terms) of WBP. One half of each group of animals will then be administered a vehicle (saline) or LPS (5 mg/kg i.p.) just before they euthanized and stress (e.g., Nf'B, cytokines) and protective (ERK) signals assessed (Figure 1). We will also determine levels of OX-6, a marker of microglial activation, as well as differences in microglial morphology. A subset of animals will be euthanized at each time-point for assessment of stress signaling and tissue levels of the polyphenols.
AIM 2 - We will also compare and correlate the degree of alterations in the various signals to the rats’ behavioral (e.g., radial arm water maze, and various motor tests e.g., rotorod) performance. Additionally, using bromodeoxyuridine (BrdU) to identify areas of the dentate gyrus showing increased DNA incorporation (an indicator of cell proliferation) and neuronal (Ngn2) and glial (GFAP) markers, we will determine differences in neurogenesis among the various groups. Dr. Kalt will measure tissue levels of polyphenols to assess bioavailability of the various WBP doses.