Abstract # 2049 Age dependent hypothalamic and pituitary responses to novel environment stress or lipopolysaccharide in rats

Previously, we have shown that nuclear factor interleukin (NF-IL)6 can be used as an activation marker for inflammatory lipopolysaccharide (LPS)-induced and psychological novel environment stress (NES) in the rat brain. Here, we aimed to investigate age-dependent changes of hypothalamic and pituitary responses to NES (cage switch) or LPS (100 μg/kg) in two and 24 months old rats. In the old rats, telemetric recording showed enhanced and prolonged NES-induced hyperthermia, which was accompanied by increased hypothalamic IL-6 mRNA expression and overall higher plasma corticosterone levels while corticotropin-releasing hormone mRNA-expression was only increased in young rats 90min after NES. Immunohistochemical analysis revealed a significant upregulation of NF-IL6-positive cells in the pituitary after NES or LPS-injection with higher numbers of NF-IL6 or NF-IL6-CD68-positive cells in the median eminence (LPS) or posterior pituitary (NES) of old rats compared to the young counterparts. Moreover, LPS-treatment significantly upregulated the secretion of the cytokines IL-6 and TNF α into supernatants of primary cell cultures of the anterior pituitary. Incubation with IL-6 and IL-10 antibodies prior to LPS-stimulation led to a robust decrease of IL-6- and an increase of TNF α -production by the pituitary cells in young but not in old rats. Overall, we show a prolonged hyperthermic and inflammatory response in aged animals to LPS and NES, which is linked to dysregulated pituitary cytokine interactions and modified brain cell activation (NF-IL6) in the hypothalamus-pituitary-adrenal axis.