論文

査読有り 国際誌
2018年9月

Inflammasome-derived cytokine IL18 suppresses amyloid-induced seizures in Alzheimer-prone mice

Proceedings of the National Academy of Sciences of the United States of America
  • Te-Chen Tzeng
  • ,
  • Yuto Hasegawa
  • ,
  • Risa Iguchi
  • ,
  • Amy Cheung
  • ,
  • Daniel R. Caffrey
  • ,
  • Elizabeth Jeanne Thatcher
  • ,
  • Wenjie Mao
  • ,
  • Gail Germain
  • ,
  • Nelsy DePaula Tamburro
  • ,
  • Shigeo Okabe
  • ,
  • Michael T. Heneka
  • ,
  • Eicke Latz
  • ,
  • Kensuke Futai
  • ,
  • Douglas T. Golenbock

115
36
開始ページ
9002
終了ページ
9007
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1073/pnas.1801802115

Alzheimer's disease (AD) is characterized by the progressive destruction and dysfunction of central neurons. AD patients commonly have unprovoked seizures compared with age-matched controls. Amyloid peptide-related inflammation is thought to be an important aspect of AD pathogenesis. We previously reported that NLRP3 inflammasome KO mice, when bred into APPswe/PS1ΔE9 (APP/PS1) mice, are completely protected from amyloid-induced AD-like disease, presumably because they cannot produce mature IL1β or IL18. To test the role of IL18, we bred IL18KO mice with APP/PS1 mice. Surprisingly, IL18KO/APP/PS1 mice developed a lethal seizure disorder that was completely reversed by the anticonvulsant levetiracetam. IL18-deficient AD mice showed a lower threshold in chemically induced seizures and a selective increase in gene expression related to increased neuronal activity. IL18-deficient AD mice exhibited increased excitatory synaptic proteins, spine density, and basal excitatory synaptic transmission that contributed to seizure activity. This study identifies a role for IL18 in suppressing aberrant neuronal transmission in AD.

リンク情報
DOI
https://doi.org/10.1073/pnas.1801802115
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30127003
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130368
ID情報
  • DOI : 10.1073/pnas.1801802115
  • PubMed ID : 30127003
  • PubMed Central 記事ID : PMC6130368

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