|CAHOON, DANIELLE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 10/12/2021
Publication Date: 11/9/2021
Citation: Cahoon, D., Fisher, D.R., Shukitt Hale, B. 2021. Blueberry extract attenuates neuroinflammation and oxidative stress when administered before and/or after lipopolysaccharide in rat microglial cells. [abstract]. 2021 Society for Neuroscience Annual Meeting. Program #181.07.
Technical Abstract: Microglia, the primary immune cells of the central nervous system (CNS), are key regulators of inflammation and oxidative stress (OS) in the CNS. In response to stress, activated microglia produce inflammatory cytokines and oxidants to eliminate pathogens and initiate repair. However, overactivation of microglia can be neurotoxic, resulting in reactive microgliosis, a feed-forward amplification of inflammation and neuronal damage. Therefore, microglial activation can continue after removal of the initiating stimulus, leading to chronic inflammation, OS, and neuro-degeneration. Blueberries (BB), rich in anti-inflammatory and antioxidant polyphenols, have been shown to reduce inflammation and OS when administered to microglia before stressors such as lipopolysaccharide (LPS), but the therapeutic value of BBs administered after microglial activation has not been examined. This study investigated the differential effects of pre-, post-, and pre-/post-BB on LPS-induced inflammation and OS in microglia. HAPI rat microglia were pre-treated with freeze-dried BB diluted in media (0.5 mg/mL) or control media (C) for 24h, incubated overnight with LPS (0 or 200 ng/mL), and post-treated with BB or C for 24h. Griess methods, ELISA, and Western blot were used to measure biomarkers of inflammation (nitrite, tumor necrosis factor-' [TNF'], inducible nitric oxide synthase [iNOS], cyclooxygenase-2 [COX-2], phosphorylated IKB' [pIKB']) and OS (NADPH oxidase [NOX2]). Data were analyzed using two-way ANOVAs with BB treatment period and LPS exposure as experimental factors. Post-hoc testing was performed using Tukey’s test. Results showed that LPS increased nitrite, TNF', iNOS, COX2, pIKB', and NOX2 compared to non-stressed control conditions (P < 0.05) and BB before and/or after LPS significantly reduced all markers compared to no BB (P < 0.05). BB treatment period did not produce significantly different attenuating effects on LPS-induced iNOS, pIKB', and NOX2. However, pre-BB was more effective than post-BB at reducing nitrite, TNF', and COX2 (P < 0.05). Pre-BB was also more effective than pre/post-BB at attenuating LPS-induced nitrite and TNF' (P < 0.05). Results suggest that BBs can target the downstream effects of microglial activation in addition to preventing stressor-induced neuroinflammation and OS. Therefore, although potentially more effective, BBs may not need to be present prior to microglial activation for beneficial effects. These findings provide evidence to support that dietary iterventions may be effective even after initiation of disease processes such as microglial-induced neuroinflammation and OS.