Poster Presentation The International Congress of Neuroendocrinology 2014

Estradiol, synthesized by reactive astrocytes, is a potent anti-inflammatory following neural damage. (#297)

Colin J Saldanha 1 , Alyssa L Pedersen 1 , Lars Nelson 1
  1. The American University, Washington, DC, United States

Injury to the avian and mammalian brain increases the expression of aromatase and cytokines in astroglia and microglia respectively.  The induced synthesis of estrogens by glial aromatization may be protective and reparative, as it decreases apoptosis and increases cyto- and neurogenesis.  How (and if) induced glial estradiol (E2) synthesis interacts with inflammatory cascades, however, remains poorly understood.  Since circulating E2 has been shown to decrease inflammation, we hypothesized that induced astrocytic aromatization may serve to decrease neuro-inflammation following brain injury, via the synthesis provision of neural E2 around the site of damage.  In three separate experiments on adult zebra finches of both sexes we tested the influence of (a) mechanical brain injury (MBI), (b) inhibition of induced aromatase expression, and (c) inhibition of induced aromatase with replacement of E2 centrally, on the expression of the pro-inflammatory cytokines TNFa, IL-1b, and IL-6, and aromatase.  In both sexes, MBI increased (p=0.03) and tended to elevate (p<0.1) TNFa and IL-1b respectively, at 2hr but not 24hr post-injury.  At the latter timepoint, when cytokines have returned to baseline, aromatase is robustly elevated in both sexes (p<0.05).  Pharmacological inhibition of induced aromatization resulted in sustained neuroinflammation, since administration of fadrozole increased TNFa (in females (p=0.04)) and IL-1b (in males (p=0.01)) 24hr following MBI.  This prolonged neuroinflammation following aromatase inhibition appears to be due a failure to synthesize E2 locally, since E2 replacement lowered TNFa and IL-1b relative to fadrozole alone.  IL-6 was not affected by MBI, aromatase inhibition or E2 replacement in either sex. These data suggest that astrocytic E2 synthesis following MBI is a potent and inducible anti-inflammatory signal, with specific modulation of discrete cytokines signaling.  Induced neural provision of E2 following damage and compromise of central pathways may protect the brain from the deleterious effects of prolonged neuroinflammation.