Effects of intrahippocampal CT105, a carboxyl terminal fragment of beta-amyloid precursor protein,alone/with inflammatory cytokines on working memory in rats |
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Authors: | Matsumoto Yuji Watanabe Shigenori Suh Yoo-Hun Yamamoto Tsuneyuki |
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Institution: | Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan. |
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Abstract: | 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. |
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Keywords: | carboxyl terminal fragment of β-amyloid precursor protein hippocampus inflammatory cytokine working memory |
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