Aging leads to altered microglial function that reduces brain resiliency increasing vulnerability to neurodegenerative diseases

Abstract

Aging is the primary risk factor for many neurodegenerative diseases. Thus, understanding the basic biological changes that take place with aging that lead to the brain being less resilient to disease progression of neurodegenerative diseases such as Parkinson's disease or Alzheimer's disease or insults to the brain such as stroke or traumatic brain injuries. Clearly this will not cure the disease per se, yet increasing the ability of the brain to respond to injury could improve long term outcomes. The focus of this review is examining changes in microglia with age and possible therapeutic interventions involving the use of polyphenol rich dietary supplements.

Keywords: Microglia; Polyphenol.

Figure 1

Bargraph showing that treatment of NPC’s with old rat serum reduces the MTT signal (1A), whereas the serum from old rats treated with NT-020 shows MTT significantly higher than that found with old rat serum (One-way ANOVA F (2,12)=65.45 followed by Sidak’s multiple comparison test * p<0.05; ** p<0.001). In 1B there is a significant negative effect of old rat serum on the number of dividing stem cells measured with BrDU, and this is reversed with the serum from old rats fed NT-020 (One-way ANOVA F (2,17)=13.64, followed by Sidak’s multiple comparison test *** p<0.001 and * p<0.05).

Figure 2

Bargraphs showing numbers of cells with nuclear-localization of Nrf2 (A) or HO-1 (B). Below are confocal images (C) of microglia from aged control or NT-020 fed rats. Confocal microscopy was used to examine the nuclear localization of Nrf2. Cellular markers were used to determine specific localization in microglia with IBA-1. Here are shown a few examples of the confocal images demonstrating nuclear (DAPI, blue) co-localization of Nrf-2 (green) IBA-1 (red) positive cells in the NT-020 treated aged rats. Z-stacks (1 micron) were taken and rotated in 2 dimensions as shown in the side panels of the figures on the left of each subpanel for control and NT-020 treated rats. Higher power images are inserted to the right of each image focusing on the cell at the center of the Z-stack rotations. Only cells with clear co-labeling from all 3 views were counted. Cells shown for control (large arrows) clearly show no co-localization. Cells shown in NT-020 panel (arrowheads) demonstrate nuclear co-localization.