Astrocyte Activation is Increased in a Rat Endometriosis Model

Abstract

Peripheral inflammation produces an immune response in the brain by the activation of microglia and astrocytes. Astrocytes are also involved in the pain symptoms of chronic diseases such as endometriosis, which is characterized by the growth of uterine tissue outside the reproductive organs. Studies using a mouse model of endometriosis found an increase in astrocytes in the spinal cord but effects in the various brain regions such as the hippocampus are still unknown. However, decreased grey matter value in women with endometriosis experiencing chronic pelvic pain suggests the involvement of the central nervous system. Previous studies in our lab found an increase in hyperalgesia symptoms in a rat model of endometriosis, however, the activation of glia cells such astrocytes and microglia in the central nervous system is still unknown.AimStudy the effects of endometriosis on astrocyte and microglia activation in the hippocampus.MethodsEndometriosis was induced by implanting uterine tissue in the intestinal mesentery in female Sprague Dawley rats that weighed more than 200g (ENDO group). Control animals received only sutures in the same region (SHAM). Sixty days after the induction of endometriosis, both groups underwent behavioral testing using open field followed by sacrifice to collect brain and endometrial tissue. Brain sections were stained against the astrocyte marker, Glial Fibric Acid Protein (GFAP), and the microglia marker, ionized calcium‐binding adapter molecule 1 (IBA‐1), and both the percent area and number and length of projections was measured using ImageJ.ResultsThe ENDO group developed vesicles with a mean total area of 49.67 mm2, indicating development of endometriosis. The ENDO group showed no significant differences in entries to the center of the open field arena (p>0.05; n=4–6), however they had significantly less velocity and travelled less distance compared with the SHAM group (p<0.05; n=4–6). Brain immunofluorescence shows an increase in the percent of area of GFAP positive staining, and an increase in the number and length of astrocyte projections in the hippocampus in the ENDO group compared with the SHAM (p<0.05; n=4–6). No significant differences were found with microglia.ConclusionsOur results demonstrate the possible involvement of astrocytes in the brain of the rat endometriosis model. Astrocyte activation in the hippocampus may be associated with peripheral inflammation and contribute to the hyperalgesia and depressive behavior often associated with endometriosis.Support or Funding InformationSupported in part by P20 GM103475‐16 & R15AT009915.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.