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Prominent microglia...
Prominent microglial inclusions in transgenic mouse models of alpha-synucleinopathy that are distinct from neuronal lesions
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- Tanrioever, Gaye (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany; Univ Tubingen, Germany
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- Bacioglu, Mehtap (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany; Univ Tubingen, Germany; Univ Tubingen, Germany
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- Schweighauser, Manuel (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany; Univ Tubingen, Germany
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- Mahler, Jasmin (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany; Univ Tubingen, Germany
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- Wegenast-Braun, Bettina M. (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany; Univ Tubingen, Germany
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- Skodras, Angelos (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany; Univ Tubingen, Germany
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- Obermueller, Ulrike (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany; Univ Tubingen, Germany
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- Barth, Melanie (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany; Univ Tubingen, Germany; Univ Tubingen, Germany
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- Kronenberg-Versteeg, Deborah (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany; Univ Tubingen, Germany
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- Nilsson, Peter (författare)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Shimshek, Derya R. (författare)
- Novartis Pharma AG, Switzerland
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- Kahle, Philipp J. (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany; Univ Tubingen, Germany; Univ Tubingen, Germany
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- Eisele, Yvonne S. (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany; Univ Tubingen, Germany; Univ Pittsburgh, PA USA
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- Jucker, Mathias (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany; Univ Tubingen, Germany
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(creator_code:org_t)
- 2020-08-12
- 2020
- Engelska.
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Ingår i: Acta neuropathologica communications. - : BMC. - 2051-5960. ; 8:1
- Relaterad länk:
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https://liu.diva-por... (primary) (Raw object)
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https://actaneurocom...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Alpha-synucleinopathies are a group of progressive neurodegenerative disorders, characterized by intracellular deposits of aggregated alpha-synuclein (alpha S). The clinical heterogeneity of these diseases is thought to be attributed to conformers (or strains) of alpha S but the contribution of inclusions in various cell types is unclear. The aim of the present work was to study alpha S conformers among different transgenic (TG) mouse models of alpha-synucleinopathies. To this end, four different TG mouse models were studied (Prnp-h[A53T]alpha S; Thy1-h[A53T]alpha S; Thy1-h[A30P]alpha S; Thy1-m alpha S) that overexpress human or murine alpha S and differed in their age-of-symptom onset and subsequent disease progression. Postmortem analysis of end-stage brains revealed robust neuronal alpha S pathology as evidenced by accumulation of alpha S serine 129 (p-alpha S) phosphorylation in the brainstem of all four TG mouse lines. Overall appearance of the pathology was similar and only modest differences were observed among additionally affected brain regions. To study alpha S conformers in these mice, we used pentameric formyl thiophene acetic acid (pFTAA), a fluorescent dye with amyloid conformation-dependent spectral properties. Unexpectedly, besides the neuronal alpha S pathology, we also found abundant pFTAA-positive inclusions in microglia of all four TG mouse lines. These microglial inclusions were also positive for Thioflavin S and showed immunoreactivity with antibodies recognizing the N-terminus of alpha S, but were largely p-alpha S-negative. In all four lines, spectral pFTAA analysis revealed conformational differences between microglia and neuronal inclusions but not among the different mouse models. Concomitant with neuronal lesions, microglial inclusions were already present at presymptomatic stages and could also be induced by seeded alpha S aggregation. Although nature and significance of microglial inclusions for human alpha-synucleinopathies remain to be clarified, the previously overlooked abundance of microglial inclusions in TG mouse models of alpha-synucleinopathy bears importance for mechanistic and preclinical-translational studies.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Synuclein; Microglia; Inclusion; Prion-like; Amyloid; Conformation; Parkinsons disease
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Tanrioever, Gaye
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Bacioglu, Mehtap
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Schweighauser, M ...
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Mahler, Jasmin
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Wegenast-Braun, ...
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Skodras, Angelos
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Obermueller, Ulr ...
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Barth, Melanie
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Kronenberg-Verst ...
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Nilsson, Peter
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Shimshek, Derya ...
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Kahle, Philipp J ...
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Eisele, Yvonne S ...
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Jucker, Mathias
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Neurovetenskaper
- Artiklar i publikationen
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Acta neuropathol ...
- Av lärosätet
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Linköpings universitet