Changes in Inflammatory Response, Redox Status and Na+, K+-ATPase Activity in Primary Astrocyte Cultures from Female Wistar Rats Subject to Ovariectomy.

Abstract

Astrocytes are dynamic glial cells that maintain brain homeostasis, particularly metabolic functions, inflammatory response, and antioxidant defense. Since menopause may be associated with brain dysfunction, in the present study, we evaluated anti- and proinflammatory cytokine release in cortical and hippocampal astrocyte cultures obtained from adult female Wistar rats subjected to ovariectomy, a known experimental model of menopause. We also tested some parameters of metabolic functionality (Na+, K+-ATPase activity) and cellular redox status, such as antioxidant enzyme defenses (superoxide dismutase and catalase) and the intracellular production of reactive oxygen species in this experimental model. Female adult Wistar rats (180 days-age) were assigned to one of the following groups: sham (submitted to surgery without removal of the ovaries) and ovariectomy (submitted to surgery to removal of the ovaries). Thirty days after ovariectomy or sham surgery, we prepared astrocyte cultures from control and ovariectomy surgery animals. Ovariectomized rats presented an increase in pro-inflammatory cytokines (tumor necrosis factor α, interleukins 1β, 6, and 18) and a decrease in interleukin 10 release, an anti-inflammatory cytokine, in cortical and hippocampal astrocytes, when compared to those obtained from sham group (control). In addition, Na+,K+-ATPase activity decreased in hippocampal astrocytes, but not in cortical astrocyte cultures. In contrast, antioxidant enzymes did not alter in cortical astrocyte cultures, but increased in hippocampal astrocytes. In summary, our findings suggest that ovariectomy is able to induce an inflammatory response in vivo, which could be detected in in vitro astrocytes after approximately 4 weeks.