Endotoxin-induced changes in human working and declarative memory associate with cleavage of plasma "readthrough" acetylcholinesterase

Osnat Cohen, Abraham Reichenberg, Chava Perry, Dalia Ginzberg, Thomas Pollmächer, Hermona Soreq*, Raz Yirmiya

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Endotoxin stimulation of the immune system produces marked alterations in memory functioning. However, molecular links between this cognitive response and infection-responding neurotransmission pathways are still unknown. The cytokine and memory responses of volunteers injected with 0.8 ng/kg Salmonella endotoxin were compared with changes in plasma levels and integrity of the stress-induced acetylcholinesterase variant, AChE-R. Vascular endothelial cells were found to express AChE-R messenger RNA and protein both in healthy and inflamed human tissues. Plasma AChE activity was reduced after endotoxin treatment, but not placebo treatment, parallel to the decline in cortisol after the endotoxin-induced peak and inversely to the accumulation of a C-terminal immunopositive AChE-R peptide of 36 amino acid residues. AChE-R cleavage coincided with significant endotoxin-induced improvement in working memory and impairment in declarative memory. By 3 h posttreatment, working memory improvement was negatively correlated with AChE-R cleavage, which showed association to proinflammatory cytokine levels. By 9 h posttreatment, declarative memory impairment was negatively correlated with AChE-R cleavage and positively correlated with the suppressed AChE activity. Endotoxin-induced peripheral cholinergic stress responses are hence associated with greater impairment in declarative memory and lower improvement in working memory, pointing at AChE-R as a surrogate marker of psychoneuroimmunological stress.

Original languageAmerican English
Pages (from-to)199-212
Number of pages14
JournalJournal of Molecular Neuroscience
Volume21
Issue number3
DOIs
StatePublished - 2003

Bibliographical note

Funding Information:
The authors are grateful to Dr. David Glick, Jerusalem, for critically reviewing this manuscript. This study was supported by the German-Israeli Foundation for Scientific Research and Development (grant no. I-495-135 to R.Y. and T.P.), US Department of Defense, DARPA (grant no. N65236-98-15411 to H.S.), and by Ester Neuroscience, Ltd.

Keywords

  • Acetylcholinesterase
  • Cortisol
  • Cytokines
  • Declarative memory
  • Endotoxin
  • Inflammation
  • Working memory

Fingerprint

Dive into the research topics of 'Endotoxin-induced changes in human working and declarative memory associate with cleavage of plasma "readthrough" acetylcholinesterase'. Together they form a unique fingerprint.

Cite this