Abstract # 1771 Experimental procedures performed sequentially exert a stress that activates caspase-1 and impairs memory in mice

Abstract

Various forms of psychological and physical stress, such as restraint and chronic mild stress, have been shown to activate the neuroimmune system and lead to cognitive impairment and depressive-like behaviors. Additionally, it has been shown that minor environmental changes, and even changes in gender, can induce stress responses in mice. Many of these models show increases in the pro-inflammatory cytokine IL-1 β . IL-1 β is produced in an inactive form and requires activation by caspase-1, which is activated by the sensing of a danger signal by the inflammasome complex. However, the danger signals responsible for these changes remains unknown. Here, we show that a novel stressor paradigm of common experimental procedures (weighing, scruffing, and needle pricks) performed sequentially can activate caspase-1 and impair memory which is dependent on adenosine signaling. 6 hr of stress increases caspase-1 activity 2–3 fold in the amygdala, hippocampus, and prefrontal cortex and impairs novel object recognition. However, 3 hr of stress was unable to change object recognition memory. Additionally, stress-induced memory impairment and caspase-1 activation can be blocked by IP administration of the pan-adenosine receptor antagonist caffeine. Finally, we show that stress-induced memory impairment can also be blocked by genetic knockout of the adenosine A2 receptor (A2AR). Taken together, these data show that common experimental techniques can exert a stress response in mice that is dependent on adenosine-induced caspase-1 activation.