Cytokines and cholinergic signals co-modulate surgical stress-induced changes in mood and memory

Irit Shapira-Lichter, Benzion Beilin, Keren Ofek, Hanna Bessler, Michal Gruberger, Yehuda Shavit, Dan Seror, Galina Grinevich, Eldad Posner, Abraham Reichenberg, Hermona Soreq, Raz Yirmiya*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Inflammatory cytokines and the cholinergic system have been implicated in the effects of stressors on mood and memory; however, the underlying mechanisms involved and the potential interrelationships between these pathways remain unclear. To address these questions, we administered neuropsychological tests to 33 generally healthy surgery patients who donated blood samples several days prior to undergoing moderate surgery (baseline), on the morning of the surgery (i.e., a psychological stressor), and one day after surgery. Eighteen control subjects were similarly tested. Serum levels of inflammatory cytokines, acetylcholinesterase (AChE) activity, and the stressor-inducible AChE-R variant were measured. An elevation in anxiety levels, an increase in depressed mood, and a decline in declarative memory were observed on the morning of the surgery, prior to any medical intervention, and were exacerbated one day after surgery. The surgical stressor-induced elevated IL-1β levels, which contributed to the increased depressed mood and to the post-surgery increase in AChE-R expression. The latter increase, which was also predicted by pre-surgery AChE-R and post-surgery mood disturbances, was associated with exacerbated memory impairments induced by surgery. In addition, elevated levels of AChE-R on the morning of the surgery predicted the post-surgery elevation in IL-6 levels, which was associated with amelioration of the memory impairments induced by surgery. Taken together, these findings suggest that exposure to a surgical stressor induces a reciprocal up-regulation of AChE-R and pro-inflammatory cytokines, which are involved in regulating the surgery-induced mood and memory disturbances.

Original languageAmerican English
Pages (from-to)388-398
Number of pages11
JournalBrain, Behavior, and Immunity
Issue number3
StatePublished - Mar 2008

Bibliographical note

Funding Information:
This study was supported by grants from the Israel Science Foundation (to R.Y.), as well as by the European Alternative Splicing Network of Excellence-EURASNET LSH-2004-1.1.5-3, the United States-Israel Binational Science Foundation (BSF No. 2003028-01) and the German Israel Project DIP-G 3.2 (to H.S.). I.S.-L. was the incumbent of an Interdisciplinary Center of Neuronal Computation (ICNC) pre-doctoral fellowship.


  • Acetylcholinesterase [AChE]
  • Anxiety
  • Interleukin-1 [IL-1]
  • Interleukin-6 [IL-6]
  • Memory
  • Mood
  • Stress
  • Surgery


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