Handling stress impairs learning through a mechanism involving caspase-1 activation and adenosine signaling

Publication date: Available online 17 May 2019Source: Brain, Behavior, and ImmunityAuthor(s): Albert E. Towers, Maci L. Oelschlager, Madelyn Lorenz, Stephen J. Gainey, Robert H. McCusker, Steven A. Krauklis, Gregory G. FreundAbstractAcute stressors can induce fear and physiologic responses that prepare the body to protect from danger. A key component of this response is immune system readiness. In particular, inflammasome activation appears critical to linking stress to the immune system. Here, we show that a novel combination of handling procedures used regularly in mouse research impairs novel object recognition (NOR) and activates caspase-1 in the amygdala. In male mice, this handling-stress paradigm combined weighing, scruffing and sham abdominal injection once per hr. While one round of weigh/scruff/needle-stick had no impact on NOR, two rounds compromised NOR without impacting location memory or anxiety-like behaviors. Caspase-1 knockout (KO), IL-1 receptor 1 (IL-1R1) KO and IL-1 receptor antagonist (IL-RA)-administered mice were resistant to handling stress-induced loss of NOR. In addition, examination of the brain showed that handling stress increased caspase-1 activity 85% in the amygdala without impacting hippocampal caspase-1 activity. To delineate danger signals relevant to handling stress, caffeine-administered and adenosine 2A receptor (A2AR) KO mice were tested and found resistant to impaired learning and caspase-1 activation. Finally, mice treated with the β-...

Source: Brain, Behavior, and Immunity - May 18, 2019 Category: Neurology Source Type: research