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2021 Fiscal Year Research-status Report

Functional analysis of astrocytes by using experimental autoimmune encephalomyelitis animal model (EAE)

Research Project

Project/Area Number 20K16468
Research InstitutionJuntendo University

Principal Investigator

COSSU DAVIDE  順天堂大学, 健康総合科学先端研究機構, 非常勤助教 (90867326)

Project Period (FY) 2020-04-01 – 2023-03-31
KeywordsParkin / Pink1 / EAE / neuroinflammation / astrocytes / microglia / peripheral immunitty / BCG
Outline of Annual Research Achievements

To study the pathological mechanisms underlying neurodegeneration, we used a combined animal model: EAE, as a model of acute central nervous system inflammation, in Parkin and Pink1 knockout mice, which are a genetic model of Parkinson’s disease.
At first, we demonstrated that Parkin is a critical regulator of immunity, as the absence of this proteins worsen the acute inflammation caused by active EAE. Then, we found that Parkin and Pink1 proteins play an age-related role in the modulating of peripheral inflammatory response during EAE, potentially contributing to the pathogenesis of neuroinflammatory and neurodegenerative conditions.

Current Status of Research Progress
Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

Since Pink1 acts upstream Parkin in a common pathway, we hypothesized that the systemic deletion of Pink1 could also modify the clinical course of EAE. However,we found a different peripheral immune modulation between Pin1- and Parkin ko mice during EAE. Indeed, an increased number of encephalitogenic CD8 T cells were detected only in the periphery of young Parkin mice, while an increased number of dendritic cells was detected in the aged Parkin and Pink1 ko mice whose did not show recovery.
Furthermore, we also investigated the efficacy of the BCG vaccine in suppressing neuroinflammation. Preliminary data showed that BCG had an age-associated protective effect against EAE via differentiation of glial cells toward an anti-inflammatory phenotype.

Strategy for Future Research Activity

1) To investigate for the first time if systemic deletion of LRRK2 could alter the clinical course of EAE, modulating the peripheral and central nervous system immune responses, focusing on microglia and astrocytes.

2)To study the mechanism behind the neuroprotective effect of BCG in active and spontaneous models of EAE, by using transgenic B2D, Pink1 ko, and Parkin ko mice.

Causes of Carryover

To perform new experiments. Cost to publish in scientific journals.

  • Research Products

    (5 results)

All 2022 2021

All Journal Article (4 results) (of which Open Access: 2 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Efficacy of BCG vaccine in animal models of neurological disorders2022

    • Author(s)
      Cossu Davide、Ruberto Stefano、Yokoyama Kazumasa、Hattori Nobutaka、Sechi Leonardo A
    • Journal Title

      Vaccine

      Volume: 40 Pages: 432~436

    • DOI

      10.1016/j.vaccine.2021.12.005

  • [Journal Article] Editorial: A Microbial View of Central Nervous System Disorders: Interplay Between Microorganisms, Neuroinflammation and Behaviour2021

    • Author(s)
      Cossu Davide、Watson Robert O.、Farina Cinthia
    • Journal Title

      Frontiers in Immunology

      Volume: 12 Pages: 1~3

    • DOI

      10.3389/fimmu.2021.816227

    • Open Access
  • [Journal Article] PARKIN modifies peripheral immune response and increases neuroinflammation in active experimental autoimmune encephalomyelitis (EAE)2021

    • Author(s)
      Cossu Davide、Yokoyama Kazumasa、Sato Shigeto、Noda Sachiko、Sechi Leonardo A.、Hattori Nobutaka
    • Journal Title

      Journal of Neuroimmunology

      Volume: 359 Pages: 577694~577694

    • DOI

      10.1016/j.jneuroim.2021.577694

  • [Journal Article] Potential of PINK1 and PARKIN Proteins as Biomarkers for Active Multiple Sclerosis: A Japanese Cohort Study2021

    • Author(s)
      Cossu Davide、Yokoyama Kazumasa、Sechi Leonardo Antonio、Hattori Nobutaka
    • Journal Title

      Frontiers in Immunology

      Volume: 12 Pages: 1~7

    • DOI

      10.3389/fimmu.2021.681386

    • Open Access
  • [Presentation] BCG-Tokyo 172 vaccination induces neuroprotection in spontaneous relapsing-remitting EAE2021

    • Author(s)
      Cossu Davide, Yokoyama Kazumasa, Hattori Nobutaka. Sechi Leonardo Antonio
    • Organizer
      41st Annual Congress of European Society of Mycobacteriology,
    • Int'l Joint Research

URL: 

Published: 2022-12-28  

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