Restraining tumor necrosis factor-alpha by thalidomide prevents the Amyloid beta-induced impairment of recognition memory in mice

Tursun Alkam, Atsumi Nitta, Hiroyuki Mizoguchi, Kuniaki Saito, Mitsuru Seshima, Akio Itoh, Kiyofumi Yamada, Toshitaka Nabeshima

研究成果: Article査読

81 被引用数 (Scopus)

抄録

No effective remedy has currently been realized to prevent the cognitive impairments of Alzheimer's disease (AD). The interruption of the toxic pathways of amyloid beta peptide (Aβ) still remains promising for the treatment. The involvement of tumor necrosis factor-alpha (TNF-α) in the toxicity of Aβ1-40 in recent reports provide a fresh target for the interruption. In the current study, we evaluated the feasibility of a strategy that target TNF-α to prevent the impairment of memory induced by Aβ. The i.c.v-injection of Aβ25-35 increased the hippocampal mRNA expression of both TNF-α and inducible nitric oxide synthase (iNOS), of which the former was stronger. The knock-out of TNF-α (TNF-α (-/-)) in mouse prevented the increase of iNOS mRNA induced by Aβ25-35. Not only the inhibition of iNOS activity but also TNF-α (-/-) prevented the nitration of proteins in the hippocampus and the impairment of recognition memory in mice induced by Aβ25-35. Daily treatment with thalidomide (20 mg/kg), a preferential degrader of TNF-α mRNA, or i.c.v.-injection of an anti-TNF-α antibody (10 ηg/mouse) prevented the nitration of proteins in the hippocampus and the impairment of recognition memory induced by Aβ25-35 or Aβ1-40 in mice. These results suggested the practicability of targeting TNF-α as a preventive strategy against Aβ-mediated cognitive impairments.

本文言語English
ページ(範囲)100-106
ページ数7
ジャーナルBehavioural Brain Research
189
1
DOI
出版ステータスPublished - 16-05-2008
外部発表はい

All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience

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