Abstract
Acute 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-adrenergic receptor antagonist, propranolol, were resistant to handling stress-induced loss of NOR and caspase-1 activation. Taken together, these results indicate that handling stress-induced impairment of object learning is reliant on a pathway requiring A2AR-dependent activation of caspase-1 in the amygdala that appears contingent on β-adrenergic receptor functionality.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 763-776 |
| Number of pages | 14 |
| Journal | Brain, Behavior, and Immunity |
| Volume | 80 |
| DOIs | |
| State | Published - Aug 2019 |
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Keywords
- Adenosine
- Amygdala
- Caffeine
- Caspase-1
- Learning
- Stress
- β-Adrenergic receptor
ASJC Scopus subject areas
- Immunology
- Endocrine and Autonomic Systems
- Behavioral Neuroscience
Cite this
Handling stress impairs learning through a mechanism involving caspase-1 activation and adenosine signaling. / Towers, Albert E.; Oelschlager, Maci L.; Lorenz, Madelyn; Gainey, Stephen J.; McCusker, Robert H.; Krauklis, Steven A.; Freund, Gregory G.
In: Brain, Behavior, and Immunity, Vol. 80, 08.2019, p. 763-776.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Handling stress impairs learning through a mechanism involving caspase-1 activation and adenosine signaling
AU - Towers, Albert E.
AU - Oelschlager, Maci L.
AU - Lorenz, Madelyn
AU - Gainey, Stephen J.
AU - McCusker, Robert H.
AU - Krauklis, Steven A.
AU - Freund, Gregory G
PY - 2019/8
Y1 - 2019/8
N2 - Acute 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-adrenergic receptor antagonist, propranolol, were resistant to handling stress-induced loss of NOR and caspase-1 activation. Taken together, these results indicate that handling stress-induced impairment of object learning is reliant on a pathway requiring A2AR-dependent activation of caspase-1 in the amygdala that appears contingent on β-adrenergic receptor functionality.
AB - Acute 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-adrenergic receptor antagonist, propranolol, were resistant to handling stress-induced loss of NOR and caspase-1 activation. Taken together, these results indicate that handling stress-induced impairment of object learning is reliant on a pathway requiring A2AR-dependent activation of caspase-1 in the amygdala that appears contingent on β-adrenergic receptor functionality.
KW - Adenosine
KW - Amygdala
KW - Caffeine
KW - Caspase-1
KW - Learning
KW - Stress
KW - β-Adrenergic receptor
UR - http://www.scopus.com/inward/record.url?scp=85065858641&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065858641&partnerID=8YFLogxK
U2 - 10.1016/j.bbi.2019.05.025
DO - 10.1016/j.bbi.2019.05.025
M3 - Article
C2 - 31108171
AN - SCOPUS:85065858641
VL - 80
SP - 763
EP - 776
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
SN - 0889-1591
ER -