| Title: |
Stochastic Optical Reconstruction Microscopy Imaging of Multiple System Atrophy Inclusions Suggests Stepwise α‐Synuclein Aggregation |
| Authors: |
Vovard, Benoît; Bodin, Alexia; Gouju, Julien; de Guilhem de Lataillade, Adrien; Derkinderen, Pascal; Etcharry-Bouyx, Frédérique; Chauviré, Valérie; Guillet-Pichon, Virginie; Verny, Christophe; Letournel, Franck; Lenaers, Guy; Chevrollier, Arnaud; Codron, Philippe |
| Contributors: |
MitoVasc - Équipe MitoLab (Mitochondrial Pathophysiology) (MITOVASC-MITOLAB); MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC); Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Laboratoire de Neurobiologie et Neuropathologie; Centre Hospitalier Universitaire d'Angers (CHU Angers); Micro et Nanomédecines Translationnelles (MINT); Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS); The Enteric Nervous System in gut and brain disorders U1235 (TENS); Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE); Nantes Université - pôle Santé; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ); Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes); Centre de Référence des Maladies Neurogénétiques; Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Source: |
ISSN: 0885-3185. |
| Publisher Information: |
CCSD; Wiley |
| Publication Year: |
2024 |
| Collection: |
Université de Nantes: HAL-UNIV-NANTES |
| Subject Terms: |
α-synuclein; STORM; dementia with Lewy bodies; Parkinson’s disease; multiple system atrophy; [SDV]Life Sciences [q-bio] |
| Description: |
International audience ; Background The architecture and composition of glial (GCI) and neuronal (NCI) α‐synuclein inclusions observed in multiple system atrophy (MSA) remain to be precisely defined to better understand the disease. Methods Here, we used stochastic optical reconstruction microscopy (STORM) to characterize the nanoscale organization of glial (GCI) and neuronal (NCI) α‐synuclein inclusions in cryopreserved brain sections from MSA patients. Results STORM revealed a dense cross‐linked internal structure of α‐synuclein in all GCI and NCI. The internal architecture of hyperphosphorylated α‐synuclein (p‐αSyn) inclusions was similar in glial and neuronal cells, suggesting a common aggregation mechanism. A similar sequence of p‐αSyn stepwise intracellular aggregation was defined in oligodendrocytes and neurons, starting from the perinuclear area and growing inside the cells. Consistent with this hypothesis, we found a higher mitochondrial density in GCI and NCI compared to oligodendrocytes and neurons from unaffected donors ( P < 0.01), suggesting an active recruitment of the organelles during the aggregation process. Conclusions These first STORM images of GCI and NCI suggest stepwise α‐synuclein aggregation in MSA. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/38357858; PUBMED: 38357858 |
| DOI: |
10.1002/mds.29744 |
| Availability: |
https://hal.science/hal-04745255; https://hal.science/hal-04745255v1/document; https://hal.science/hal-04745255v1/file/Movement%20Disorders%20-%202024%20-%20Vovard%20-%20Stochastic%20Optical%20Reconstruction%20Microscopy%20Imaging%20of%20Multiple%20System%20Atrophy.pdf; https://doi.org/10.1002/mds.29744 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.C9CE6EA3 |
| Database: |
BASE |