• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Role of APLP1 and APLP2 expressed in astrocytes on astrocyte/synapse interactions and synaptic plasticity

Research Project

Project/Area Number 19F19728
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section外国
Review Section Basic Section 46010:Neuroscience-general-related
Research InstitutionInstitute of Physical and Chemical Research
Host Researcher 合田 裕紀子  国立研究開発法人理化学研究所, 脳神経科学研究センター, チームリーダー (40614897)
Foreign Research Fellow SAINT MARTIN MARGAUX  国立研究開発法人理化学研究所, 脳神経科学研究センター, 外国人特別研究員
Project Period (FY) 2019-07-24 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2020: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2019: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordsastrocyte / APP / APLP / tripartite synapse / astrocyte morphology / APLP1 / synapse
Outline of Research at the Start

The overall aim of this research is to demonstrate the role of astrocyte cell adhesion molecules APLPs in synaptic transmission and synaptic plasticity. Although APP has been widely studied in the context of Alzheimer disease, the physiological role and mechanisms of APP and the related APLPs in the nervous system has been less well documented. Importantly, the full understanding of APP/APLPs function in synapse formation and synaptic transmission could be provide new insights for the development of Alzheimer disease therapeutics.

Outline of Annual Research Achievements

To study a role for astrocyte APP and APLPs on neuron-astrocyte interactions, we confirmed astrocytic APP, APLP1 and APLP2 expression by western blot analysis of rat hippocampal culture lysates. Immunofluorescence analysis of hippocampal cultures showed the expression of APP, APLP1 and APLP2 in neurons, as expected. We also detected a strong APLP1 signal and a more limited signal for APP and APLP2 in astrocytes compared to neurons, consistent with the detection of relatively higher levels of APLP1 mRNA compared to APP or APLP2 mRNA in astrocytes in the RNA-seq analysis (unpublished). The impact of APP and APLPs as a substrate on astrocyte morphology was studied by overexpressing APP, APLP1 and APLP2 in HEK cells and culturing astrocytes over them. Neurexin-1-α, known to increase astrocyte morphological complexity, and mGFP were used as positive and negative controls, respectively. Sholl analysis showed that APLP1 and APLP2 but not APP as a substrate slightly increased the astrocyte morphological complexity. When APP, APLP1 or APLP2 in astrocytes was knocked down by shRNA (Young-Pearse et al., 2008), APP and APLP1 KD in astrocytes decreased astrocyte complexity compared to the controls. Moreover, astrocyte APLP1 KD reduced astrocyte area and branch length. No significant impact of APP, APLP1 or APLP2 KD in astrocytes on the density of excitatory or inhibitory presynaptic boutons or in their level of synaptic vesicle proteins was detected. Future work will characterize the roles of astrocyte APP and APLPs on synaptic function and also extend the analysis to the intact brain.

Research Progress Status

令和2年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和2年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2020 Annual Research Report
  • 2019 Annual Research Report

Research Products

(1 results)

All 2020

All Presentation (1 results)

  • [Presentation] Astrocyte APLPs’ role on astrocyte/synapse interaction and synaptic plasticity2020

    • Author(s)
      Margaux SAINT MARTIN
    • Organizer
      The 8th RIKEN Life Science Retreat
    • Related Report
      2020 Annual Research Report

URL: 

Published: 2019-07-30   Modified: 2021-12-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi