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Dehydroepiandrosterone inhibits microglial nitric oxide production in a stimulus‐specific manner
Author(s) -
Barger Steven W.,
Chavis Janet A.,
Drew Paul D.
Publication year - 2000
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/1097-4547(20001115)62:4<503::aid-jnr4>3.0.co;2-a
Subject(s) - nitric oxide , dehydroepiandrosterone , stimulus (psychology) , microglia , neuroscience , chemistry , endocrinology , medicine , psychology , hormone , androgen , inflammation , cognitive psychology
Dehydroepiandrosterone (DHEA) is a steroid that circulates in abundance in the form of a sulfated reserve (DHEA‐S). The levels of DHEA decline with age and further in age‐related neuropathologies, including Alzheimer disease. Because of their reported anti‐inflammatory effects, we tested the actions of these compounds on microglia. At concentrations of 3 −9 to 1 −6 M, DHEA and DHEA‐S inhibited the production of nitrite and morphological changes stimulated by lipopolysaccharide. DHEA and DHEA‐S also inhibited LPS induction of iNOS protein, but neither inhibited LPS‐induced iNOS mRNA or the activation of NF‐κB. These data suggest that the hormone regulates nitrite production through a post‐transcriptional mechanism. Interestingly, microglial nitrite production in response to a secreted form of the β‐amyloid precursor protein (sAPP) was unaffected by DHEA. Another Alzheimer‐related factor, amyloid β‐peptide, also stimulated microglial nitrite production but in a manner dependent on the co‐stimulus interferon‐γ. DHEA was found to inhibit only the interferon‐γ component of the microglial response. These data add to a growing body of evidence for differences in the profiles of mononuclear phagocytes activated by distinct stimuli. J. Neurosci. Res. 62:503–509, 2000. © 2000 Wiley‐Liss, Inc.