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P2‐198: TESTOSTERONE DEFICIENCY AGGRAVATES COGNITIVE DECLINE IN OBESE CONDITION VIA INCREASED OXIDATIVE STRESS, GLIAL ACTIVITY AND CELL APOPTOSIS IN HIPPOCAMPUS
Author(s) -
Chunchai Titikorn,
Apaijai Nattayaporn,
Keawtep Puntarik,
Mantor Duangkamol,
Arinno Apiwan,
Pratchayasakul Wasana,
Chattipakorn Nipon,
Chattipakorn Siriporn C.
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.885
Subject(s) - endocrinology , medicine , morris water navigation task , oxidative stress , insulin resistance , cognitive decline , hippocampus , testosterone (patch) , orchiectomy , obesity , biology , dementia , disease
activation of astrocytes, one of the primary immune cells of the brain. Methods: Primary mouse astrocytes were harvested from postnatal day 0-1 CD1 mice and conditioned with combinations of 50 nM heme, Hb, and Ab1-42. Cytokine expression into culture medium was analyzed using a multiplexed immunoassay (EMD Millipore). Western blot, immunocytochemistry, and phagocytosis assays were performed to quantify astrocyte scavenger activity. Size exclusion chromatography was used to identify and isolate heme and Hb bound Ab1-42 species. Results:Our work revealed that heme and Hb suppressed immune activity of primary mouse astrocytes. Both heme and Hb significantly reduced expression of a panel of inflammatory cytokines which was upregulated by Ab1-42 (p<0.01). Furthermore, both heme and Hb suppressed scavenger activity of astrocytes, as seen by decreased expression of the scavenger receptor CD36 (p<0.01), and internalization of Ab1-42. Finally, we identified that a soluble, high molecular weight (>75kDa), Ab1-42 oligomeric species is primarily responsible for astrocyte activation and that heme or Hb association with these oligomers reverses inflammation. Conclusions:Our data indicated that heme and Hb are potent modulators of astrocyte immune activity and suppress a number of critical immune functions, including the ability to clear pathogens such as Ab.