Reconstruction of single cortical projection neurons reveals primary spine loss in multiple sclerosis
Open accessAbstract
See Friese (doi: 10.1093/brain/awv349 ) for a scientific commentary on this article. Grey matter pathology has emerged as an important contributor to long-term disability in multiple sclerosis. To better understand where and how neuronal damage in the grey matter is initiated, we used high resolution confocal microscopy of Golgi-Cox impregnated tissue sections and reconstructed single cortical projection neurons in autopsies from eight patients with long-standing relapsing-remitting or secondary progressive multiple sclerosis and eight control patients without neurological disease. Analysis of several hundred individual neurons located in the insular, frontotemporal and occipital lobe revealed a widespread and pronounced loss of dendritic spines in multiple sclerosis cortex that occurs independent of cortical demyelination and axon loss. The presence of a primary synaptic pathology in the normal-appearing cortex of multiple sclerosis patients challenges current disease concepts and has important implications for our understanding of disease progression. See Friese (doi: 10.1093/brain/awv349 ) for a scientific commentary on this article. Neuronal pathology contributes to long-term disability in multiple sclerosis, but where and how this damage is initiated is unclear. Jürgens et al. use high-resolution confocal microscopy to reconstruct single cortical neurons in patients with multiple sclerosis and controls. Results reveal a primary lesion-independent synaptic pathology that challenges current disease concepts.
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Neurite morphology is affected by multiple sclerosis.
“Our study tests the hypothesis that the variability of neurite orientations is a biomarker of multiple sclerosis pathology, and is motivated by recent findings demonstrating that neurite morphology is a substrate of neural function23, 24 and is affected by multiple sclerosis.25”
From Neurite dispersion: a new marker of multiple sclerosis spinal cord pathology? (2017) · cites this paper as [25]
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- Authors
- Jürgens, T., Jafari, M., Kreutzfeldt, M., Bahn, E., Brück, W., Kerschensteiner, M., & Merkler, D.
- Affiliations
- University of Geneva (CH)
- Institut für Klinische Neuroimmunologie (DE)
- Universitätsmedizin Göttingen (DE)
- Munich Cluster for Systems Neurology (DE)
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-12-14
- Volume
- 139
- Issue
- 1
- Pages
- 39-46
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2199486318
- Cited by
- 175
- References
- 25
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 13 · 2023: 14 · 2022: 12 · 2021: 24 · 2020: 21 · 2019: 18 · 2018: 17 · 2017: 19 · 2016: 8 · 2015: 1
- FWCI
- 11.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion)
- RERO DOC (Universität Bern) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- GRO (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- National Science Foundation
- Multiple Sclerosis Society
- European Commission (2007–2013)
- Deutsche Forschungsgemeinschaft (EXC 1010)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (152928)
- Bundesministerium für Bildung und Forschung
- Schweizerische Multiple Sklerose Gesellschaft
- FP7 Ideas: European Research Council (310932)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- multiple sclerosis, dendritic spine loss, cortical projection neurons, synaptic pathology, gray matter pathology, neuronal injury, relapsing-remitting multiple sclerosis, secondary progressive multiple sclerosis, long-term disability, single-neuron reconstruction
- MeSH terms
- Cerebral Cortex, Female, Humans, Male, Middle Aged, Multiple Sclerosis, Neurons, Case-Control Studies, Dendritic Spines, Gray Matter
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