3
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Synaptopodin Deficiency Ameliorates Symptoms in the 3xTg Mouse Model of Alzheimer's Disease

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Disruption in calcium homeostasis is linked to several pathologies and is suggested to play a pivotal role in the cascade of events leading to Alzheimer's disease (AD). Synaptopodin (SP) residing in dendritic spines has been associated with ryanodine receptor (RyR), such that spines lacking SP release less calcium from stores. In this work, we mated SPKO with 3xTg mice (3xTg/SPKO) to test the effect of SP deficiency in the AD mouse. We found that 6-month-old male 3xTg/SPKO mice restored normal spatial learning in the Barns maze, LTP in hippocampal slices, and expression levels of RyR in the hippocampus that were altered in the 3xTg mice. In addition, there was a marked reduction in 3xTg-associated phosphorylated tau, amyloid β plaques, and activated microglia in 3xTg/SPKO male and female mice. These experiments indicate that a reduction in the expression of SP ameliorates AD-associated phenotype in 3xTg mice.

          SIGNIFICANCE STATEMENT This study strengthens the proposed role of calcium stores in the development of AD-associated phenotype in the 3xTg mouse model, in that a genetic reduction of the functioning of ryanodine receptors using synaptopodin-knock-out mice ameliorates AD symptoms at the behavioral, electrophysiological, and morphological levels of analysis.

          Related collections

          Author and article information

          Journal
          J Neurosci
          J. Neurosci
          jneuro
          jneurosci
          J. Neurosci
          The Journal of Neuroscience
          Society for Neuroscience
          0270-6474
          1529-2401
          15 May 2019
          15 November 2019
          : 39
          : 20
          : 3983-3992
          Affiliations
          [1] 1Departments of Neurobiology, and
          [2] 2Veterinary Resources, The Weizmann Institute, Rehovot 76100, Israel
          Author notes
          Correspondence should be addressed to Menahem Segal at menahem.segal@ 123456weizmann.ac.il

          Author contributions: M.S. designed research; E.A., E.O.-B., M.T., and D.H.M. performed research; E.O.-B. contributed unpublished reagents/analytic tools; E.A., E.O.-B., M.T., and M.S. analyzed data; M.S. wrote the paper.

          Author information
          https://orcid.org/0000-0003-0441-8757
          https://orcid.org/0000-0001-5127-6830
          https://orcid.org/0000-0001-7592-0408
          Article
          PMC6520517 PMC6520517 6520517 2920-18
          10.1523/JNEUROSCI.2920-18.2019
          6520517
          30872324
          c57d0741-b038-401a-bc5b-e8c336a65a40
          Copyright © 2019 the authors
          History
          : 15 November 2018
          : 18 January 2019
          : 18 February 2019
          Categories
          Research Articles
          Neurobiology of Disease

          LTP,calcium,hippocampus,synaptopodin,3xTg mouse
          LTP, calcium, hippocampus, synaptopodin, 3xTg mouse

          Comments

          Comment on this article