Effects of intrahippocampal CT105, a carboxyl terminal fragment of beta-amyloid precursor protein, alone/with inflammatory cytokines on working memory in rats.
In this study, we examined the effects of a 105 amino acid carboxyl terminal fragment of beta-amyloid precursor protein (CT105) and inflammatory cytokines on working memory in rats, by using a three-panel runway set-up. CT105 at 10 nmol/side significantly impaired working memory when it was administered bilaterally into the hippocampus. Furthermore, to elucidate the interaction of CT105 with inflammatory cytokines, we co-administered tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in combination with CT105. Concurrent injections of CT105 (1.0 nmol/side) and TNF-alpha (100 ng/side) produced a synergistic deficit of working memory, whereas IL-1beta (100 ng/side) combined with CT105 (1.0 nmol/side) did not affect the working memory performance. These results indicate that the CT105-induced impairment of working memory is strongly aggravated by an increase in the level of the inflammatory cytokine TNF-alpha, which may occur in the brains of patients with Alzheimer's disease.
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Yuji
Y
Matsumoto
Shigenori
S
Watanabe
Yoo-Hun
YH
Suh
Tsuneyuki
T
Yamamoto
D000544:Alzheimer Disease; D016564:Amyloid beta-Protein Precursor / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects; D016207:Cytokines / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects* / Q000502:physiology; D008845:Microinjections; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D012054:Reinforcement, Psychology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology
D016564:Amyloid beta-Protein Precursor; D016207:Cytokines; D007375:Interleukin-1; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C409682:amyloid beta-protein precursor CT105