TY - JOUR
T1 - Endotoxin-induced changes in human working and declarative memory associate with cleavage of plasma "readthrough" acetylcholinesterase
AU - Cohen, Osnat
AU - Reichenberg, Abraham
AU - Perry, Chava
AU - Ginzberg, Dalia
AU - Pollmächer, Thomas
AU - Soreq, Hermona
AU - Yirmiya, Raz
N1 - 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.
PY - 2003
Y1 - 2003
N2 - 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.
AB - 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.
KW - Acetylcholinesterase
KW - Cortisol
KW - Cytokines
KW - Declarative memory
KW - Endotoxin
KW - Inflammation
KW - Working memory
UR - http://www.scopus.com/inward/record.url?scp=3242722725&partnerID=8YFLogxK
U2 - 10.1385/JMN:21:3:199
DO - 10.1385/JMN:21:3:199
M3 - Article
C2 - 14645987
AN - SCOPUS:3242722725
SN - 0895-8696
VL - 21
SP - 199
EP - 212
JO - Journal of Molecular Neuroscience
JF - Journal of Molecular Neuroscience
IS - 3
ER -