Skip to main content
ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #341545
Title: Effect of blueberry and insulin on glucose-induced neurotoxicity in rat microglial cells

Author
item HININGER, ISABELLE - Universite Grenoble Alpes
item Thangthaeng, Nopporn
item BIELINSKI, DONNA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item Fisher, Derek
item Shukitt-Hale, Barbara
item POULOSE, SHIBU - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 7/21/2017
Publication Date: 10/3/2017
Citation: Hininger, I., Thangthaeng, N., Bielinski, D., Fisher, D.R., Shukitt Hale, B., Poulose, S. 2017. Effect of blueberry and insulin on glucose-induced neurotoxicity in rat microglial cells. 8th International Conference on Polyphenols and Health (ICPH 2017) Abstract# 03-053.

Interpretive Summary:

Technical Abstract: Growing evidence suggests that the altered glucose metabolism seen in type-2 diabetes may be responsible for memory impairment. Studies suggest that high cellular glucose causes neurotoxicity via increased generation of oxidative free radicals which may enhance neuroinflammation. Blueberries (BB) have been shown to reduce oxidative stress (OS) and neuroinflammation (INF) in animal and cell models. Insulin (INS) is a known homeostatic agent for glucose metabolism, yet its role on microglia is largely unknown. Therefore, in the present study, we explored whether microglia exposed to a high glucose media would increase expression of neuroinflammatory mediators. We hypothesize that hyperglycemia would up-regulate inflammatory mediators which would be dampened by insulin and phytochemicals found in BB. Lipopolysaccharide (LPS) is a known cerebral inflammatory molecule with concomitant induction of iNOS expression and NO production; therefore, use of LPS to study the effect of glucose and possible protection by insulin and BB phytochemicals is an appropriate model to address the research problems. HAPI rat microglial cells were cultured in different concentrations of glucose (low-5mM, medium-25mM and high-50mM) and treated with whole fruit BB pulp extracts (2% w/v) and insulin (50mM), with and without LPS treatments. Expression of iNOS, NOX4, and GLUT1 along with extracellular release of TNF-alpha and nitrite was used as outcome measures. Indices of OS and INF increased proportionally to the sugar concentration, with medium and high glucose concentrations causing significant elevation of these markers. Individually, BB significantly reduced INF and OS mediators at low and medium glucose levels, whereas insulin was effective at all three sugar concentrations. No synergistic effects were observed with the combination treatment of insulin and BB. However, when the cells were additionally stressed with LPS along with sucrose, both BB and insulin significantly lowered the LPS-induced INF and OS markers even at high sucrose levels, compared to LPS-control. These findings suggest that either BB or INS treatments can attenuate the OS-, INF-neurotoxicity under high cellular stress conditions.