Elucidation of the mechanism for neurodegeneration in prion diseases through neuron-glia cross-talk

2018 Fiscal Year Final Research Report

• Project/Area Number: 15H02475
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Hokkaido University
• Principal Investigator: HOROUICHI MOTOHIRO 北海道大学, 獣医学研究院, 教授 (30219216)
• Co-Investigator(Kenkyū-buntansha): 小林 篤史 北海道大学, 獣医学研究院, 准教授 (50431507)
• Research Collaborator: KURODA minori ; SHAN zhifu
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: プリオン / 神経細胞 / ミクログリア / アストロサイト / RNA-seq / AFT3 / 小胞体ストレス応答

Outline of Final Research Achievements

Microglia activation and astrogliosis are observed in the early stage of prion diseases. Therefore, glial activation are thought to be involved in the neurodegeneration, however, details of the mechanisms remain to be elucidated. In this study, first we analyzed the activation state of microgila and astrocyte in prion infected mice by RNA-sequencing. We also analyzed brain regions where neuronal loss was progressively observed in prion-infected mice and analyzed gene expression in the small region. Neuron-enriched genes were selected by bioinformatics and further analyses disclosed that expression of stress-induced transcriptional factor, ATF3, was induced in the lateral dorsal part of the thalamus where progressive neuronal loss was observed. The lateral dorsal part of the thalamus is one of the regions where intense glial activation is observed and thus, it is of interest to elucidate if glial activation induces STF3 induction in prion-infected neurons.

Free Research Field

獣医衛生学

Academic Significance and Societal Importance of the Research Achievements

神経変性疾患におけるグリア細胞の活性化状態の比較解析から、神経変性におけるグリア細胞の役割の理解が一層進むと思われる。本研究におけるミクログリアとアストロサイトの遺伝子発現情報は貴重な基礎データとして活用が期待されるため、独自にデータベース化して公開する方向で検討している。また、転写調節因子ATF3が神経変性機構を理解する鍵となる分子となる可能性があるため、ATF3は今後の重要な研究標的であり、その解析が進むことで、神経変性疾患の新たな治療標的となる可能性もある。