Reduced acetylcholinesterase activity downregulates peripheral and central inflammation during glucocorticoid resistance induced by chronic restraint stress and systemic lipopolysaccharide challenge in male mice

ABSTRACT

Stress sensitizes the neuroinflammatory response to immunogenic challenge and associated behavioral changes in rodents. GlucocorticoidS (GCs) have been well known for their immunosuppressive and anti-inflammatory properties. However, recent advances have uncovered situations wherein they have opposite effects, especially when activated immune cells show resistance to circulating GCs. Under these circumstances, studying the role of the recently described ‘cholinergic anti-inflammatory pathway’ was of considerable interest. In this study, we investigated the level of serum C-reactive protein (CRP), cytokines and reactive oxygen and nitrogen species and antioxidant enzyme activities in the liver, brain and adrenal gland following LPS administration in stressed mice. Hypothalamic acetyl cholinesterase (AChE) enzyme activity and the expression of heat shock proteins 70 and 90, superoxide dismutase-1 and cycloxygenase-2 proteins in the hypothalamus were estimated by immunobloting. Behavioural changes were observed on an elevated plus maze and in an open field. Our results suggest that there exists a synergistic effect between inflammation and stress only when the stress exposure is acute in nature. Immune activation following chronic stress, downregulated inflammation, in spite of the resistant endocrine response to inflammation, via the newly described cholinergic anti-inflammatory pathway. Thus, it indicates that acute immune activation during chronic stress may be beneficial for the host to maintain homeostasis.