title: Cytokines and cholinergic signals co-modulate surgical stress-induced changes in mood and memory.
abstract: 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-1 beta 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.
authors.affiliation: Department of Psychology, The Hebrew University, Jerusalem 91905, Israel.
authors.forename: Irit
authors.initials: I
authors.lastname: Shapira-Lichter
authors.forename: Benzion
authors.initials: B
authors.lastname: Beilin
authors.forename: Keren
authors.initials: K
authors.lastname: Ofek
authors.forename: Hanna
authors.initials: H
authors.lastname: Bessler
authors.forename: Michal
authors.initials: M
authors.lastname: Gruberger
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Shavit
authors.forename: Dan
authors.initials: D
authors.lastname: Seror
authors.forename: Galina
authors.initials: G
authors.lastname: Grinevich
authors.forename: Eldad
authors.initials: E
authors.lastname: Posner
authors.forename: Abraham
authors.initials: A
authors.lastname: Reichenberg
authors.forename: Hermona
authors.initials: H
authors.lastname: Soreq
authors.forename: Raz
authors.initials: R
authors.lastname: Yirmiya
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000328:Adult; D000339:Affect; D000368:Aged; D003071:Cognition; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008568:Memory; D008875:Middle Aged; D008954:Models, Biological; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D013315:Stress, Psychological / Q000523:psychology*; D013514:Surgical Procedures, Operative / Q000009:adverse effects*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D015850:Interleukin-6; D011956:Receptors, Cell Surface; D000110:Acetylcholinesterase