View in EDS

Synaptopathy in the TDP‐43ΔNLS Mouse Model of Sporadic Amyotrophic Lateral Sclerosis.

Saved in:
Bibliographic Details
Title: Synaptopathy in the TDP‐43ΔNLS Mouse Model of Sporadic Amyotrophic Lateral Sclerosis.
Authors: Ayvazian‐Hancock, Ani (AUTHOR), Butler, Emma (AUTHOR), Meehan, Claire F. (AUTHOR), Miles, Gareth B. (AUTHOR), Broadhead, Matthew J. (AUTHOR)
Source: European Journal of Neuroscience. Nov2025, Vol. 62 Issue 10, p1-19. 19p.
Subjects: Amyotrophic lateral sclerosis, Synapses, TDP-43 proteinopathies, Neurodegeneration, Cholinergic mechanisms
Abstract: Sporadic cases of amyotrophic lateral sclerosis (sALS) represent the most common form of motor neuron disease. sALS is characterised by pathological cytoplasmic inclusions of TDP‐43, so‐called reactive astrocyte pathology and motor neuron degeneration. Alterations in certain subpopulations of synapses between neurons are thought to be a key driver of the pathological mechanisms of ALS. However, we do not have a clear understanding of which types of synapses are impacted in ALS. Identifying vulnerable synapses affected in sALS models may provide insights into the key sites of disease pathogenesis. In this study we have performed quantitative high‐resolution microscopy to survey different synapse subtypes, including excitatory (glutamatergic), inhibitory (glycinergic) and modulatory (cholinergic C‐Boutons) synapses, in the spinal cord of a mouse model of sALS showing inducible TDP‐43 pathology (TDP43ΔNLS) restricted to neurons. We have identified changes in cholinergic synapses and a subpopulation of excitatory synapses. Mice display robust neuronal TDP‐43 pathology and evidence of TDP‐43 changes at cholinergic C‐boutons. We also observe no evidence of astrocytic pathology nor changes in the fraction of synapses that are contacted by astrocytes. Overall, our findings highlight the selective vulnerability of distinct synapse populations in ALS. [ABSTRACT FROM AUTHOR]
Copyright of European Journal of Neuroscience is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
FullText Text:
  Availability: 0
Header DbId: pbh
DbLabel: Psychology and Behavioral Sciences Collection
An: 189709209
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Synaptopathy in the TDP‐43ΔNLS Mouse Model of Sporadic Amyotrophic Lateral Sclerosis.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Ayvazian‐Hancock%2C+Ani%22">Ayvazian‐Hancock, Ani</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Butler%2C+Emma%22">Butler, Emma</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Meehan%2C+Claire F%2E%22">Meehan, Claire F.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Miles%2C+Gareth B%2E%22">Miles, Gareth B.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Broadhead%2C+Matthew J%2E%22">Broadhead, Matthew J.</searchLink> (AUTHOR)
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%22European+Journal+of+Neuroscience%22">European Journal of Neuroscience</searchLink>. Nov2025, Vol. 62 Issue 10, p1-19. 19p.
– Name: Subject
  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Amyotrophic+lateral+sclerosis%22">Amyotrophic lateral sclerosis</searchLink><br /><searchLink fieldCode="DE" term="%22Synapses%22">Synapses</searchLink><br /><searchLink fieldCode="DE" term="%22TDP-43+proteinopathies%22">TDP-43 proteinopathies</searchLink><br /><searchLink fieldCode="DE" term="%22Neurodegeneration%22">Neurodegeneration</searchLink><br /><searchLink fieldCode="DE" term="%22Cholinergic+mechanisms%22">Cholinergic mechanisms</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Sporadic cases of amyotrophic lateral sclerosis (sALS) represent the most common form of motor neuron disease. sALS is characterised by pathological cytoplasmic inclusions of TDP‐43, so‐called reactive astrocyte pathology and motor neuron degeneration. Alterations in certain subpopulations of synapses between neurons are thought to be a key driver of the pathological mechanisms of ALS. However, we do not have a clear understanding of which types of synapses are impacted in ALS. Identifying vulnerable synapses affected in sALS models may provide insights into the key sites of disease pathogenesis. In this study we have performed quantitative high‐resolution microscopy to survey different synapse subtypes, including excitatory (glutamatergic), inhibitory (glycinergic) and modulatory (cholinergic C‐Boutons) synapses, in the spinal cord of a mouse model of sALS showing inducible TDP‐43 pathology (TDP43ΔNLS) restricted to neurons. We have identified changes in cholinergic synapses and a subpopulation of excitatory synapses. Mice display robust neuronal TDP‐43 pathology and evidence of TDP‐43 changes at cholinergic C‐boutons. We also observe no evidence of astrocytic pathology nor changes in the fraction of synapses that are contacted by astrocytes. Overall, our findings highlight the selective vulnerability of distinct synapse populations in ALS. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of European Journal of Neuroscience is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=189709209
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1111/ejn.70320
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 19
        StartPage: 1
    Subjects:
      – SubjectFull: Amyotrophic lateral sclerosis
        Type: general
      – SubjectFull: Synapses
        Type: general
      – SubjectFull: TDP-43 proteinopathies
        Type: general
      – SubjectFull: Neurodegeneration
        Type: general
      – SubjectFull: Cholinergic mechanisms
        Type: general
    Titles:
      – TitleFull: Synaptopathy in the TDP‐43ΔNLS Mouse Model of Sporadic Amyotrophic Lateral Sclerosis.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Ayvazian‐Hancock, Ani
      – PersonEntity:
          Name:
            NameFull: Butler, Emma
      – PersonEntity:
          Name:
            NameFull: Meehan, Claire F.
      – PersonEntity:
          Name:
            NameFull: Miles, Gareth B.
      – PersonEntity:
          Name:
            NameFull: Broadhead, Matthew J.
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 15
              M: 11
              Text: Nov2025
              Type: published
              Y: 2025
          Identifiers:
            – Type: issn-print
              Value: 0953816X
          Numbering:
            – Type: volume
              Value: 62
            – Type: issue
              Value: 10
          Titles:
            – TitleFull: European Journal of Neuroscience
              Type: main
ResultId 1