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Abstract Details

Ketone Bodies Induce Oxidative Stress and Apoptosis on Human Microglial Cell Line
Neuro Trauma, Critical Care, and Sports Neurology
P15 - Poster Session 15 (12:00 PM-1:00 PM)
13-006

To investigate the effect of acetoacetate (AcAc) and 3-β-hydroxybutyrate (3HB) on human microglia cell line CHME5.

 
Diabetic ketoacidosis (DKA) has been associated with cognitive impairment and structural alterations in the brain. There is increased evidence supporting the role of neuroinflammation in causing these alterations. Ketone bodies have been reported to play a role in the pathogenesis of brain edema in DKA. However, their direct effect on microglia is unknown.   

Human microglia CHME5 cells  were treated with AcAc and 3HB at various concentrations and combinations. A series of morphological, biological and molecular responses were measured.

High and low dose of ketone bodies induced a significant and continuous increase in ROS within one hour after exposure to CHME5 cells. Upregulation in mitochondrial superoxide level was detected 5 minutes after exposure suggestive of early and selective impairment of mitochondrial function in AcAc treated CHME 5 cells. Although a reduction in cell viability with XTT was detected within 24 hours, a significant and delayed increase of apoptosis of CHME5 cells was observed 4 days after exposure to high dose of AcAc. Cytokines expression reached a peak within one hour and persisted for 3 days after exposure to ketone bodies:   only IL-13, IL-1β, and IL-6 increased more than 2-folds, which was considered a significant change. At 24 hour and 3 days, all cytokine mRNA level decreased, but IL-1β and IL-6 expression continued to significantly increase until 3 days post-treatment   

Ketone bodies induced microglia activation with early and selective impairment of mitochondrial function, increased cytokines expression and delayed increase in apoptosis. Damage of ketone bodies on microglia may be triggered by  mitochondrial damage and persistent ROS.
Authors/Disclosures
Nizar Souayah, MD, FÂ鶹´«Ã½Ó³»­ (NJMS)
PRESENTER 		Dr. Souayah has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Takeda. Dr. Souayah has received publishing royalties from a publication relating to health care.
No disclosure on file