ArticleMultiple sclerosis (Houndmills, Basingstoke, England)2022
Inhibitory synaptic loss drives network changes in multiple sclerosis: An ex vivo to in silico translational study.
Article in Multiple sclerosis (Houndmills, Basingstoke, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Neurophysiological brain function predicts response to cognitive rehabilitation and mindfulness in multiple sclerosis: a randomized trial.Journal of neurology · 2024Trial
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- Pathological extracellular matrix changes in decellularized normal appearing gray matter and subpial multiple sclerosis lesions.iScience · 2026Article
- TMS-EEG signatures of motor network dysfunction in multiple sclerosis.Brain communications · 2026Article
- Extracellular Vesicles From Multiple Sclerosis White Matter Exhibit Synaptic, Mitochondrial, Complement and Ageing-Related Pathway Dysregulation.Journal of extracellular vesicles · 2025Article
- Development of a Human Preclinical Platform for the Identification of Neuroprotective Compounds.The European journal of neuroscience · 2025Article
- A focus on the normal-appearing white and gray matter within the multiple sclerosis brain: a link to smoldering progression.Acta neuropathologica · 2025Review
- Multiple sclerosis: what have we learned and can we still learn from electron microscopy.Cellular and molecular life sciences : CMLS · 2025Review
- Task-induced 1/f slope modulation as a paradigm-independent marker of cognitive control in multiple sclerosis.Imaging neuroscience (Cambridge, Mass.) · 2025Article
- Energy Associated With Dynamic Network Changes in Patients With Multiple Sclerosis and Cognitive Impairment.Neurology · 2024Article
- Association of Cortical Lesions With Regional Glutamate, GABA,Neurology · 2024Article
- Instability of excitatory synapses in experimental autoimmune encephalomyelitis and the outcome for excitatory circuit inputs to individual cortical neurons.Brain, behavior, and immunity · 2024Article
- The NR4A2/VGF pathway fuels inflammation-induced neurodegeneration via promoting neuronal glycolysis.The Journal of clinical investigation · 2024Article
- Characterization of spinal cord tissue-derived extracellular vesicles in neuroinflammation.Journal of neuroinflammation · 2024Article
- Spatial correspondence among regional gene expressions and gray matter volume loss in multiple sclerosis.Molecular psychiatry · 2024Article
- Local signal variability and functional connectivity: Sensitive measures of the excitation-inhibition ratio?Cognitive neurodynamics · 2024Article
- The spectral slope as a marker of excitation/inhibition ratio and cognitive functioning in multiple sclerosis.Human brain mapping · 2023Article
- A vision of 14 T MR for fundamental and clinical science.Magma (New York, N.Y.) · 2023Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSynaptic and neuronal loss contribute to network dysfunction and disability in multiple sclerosis (MS). However, it is unknown whether excitatory or inhibitory synapses and neurons are more vulnerable and how their losses impact network functioning.
objectiveTo quantify excitatory and inhibitory synapses and neurons and to investigate how synaptic loss affects network functioning through computational modeling.
methodsUsing immunofluorescent staining and confocal microscopy, densities of glutamatergic and GABAergic synapses and neurons were compared between post-mortem MS and non-neurological control cases. Then, a corticothalamic biophysical model was employed to study how MS-induced excitatory and inhibitory synaptic loss affect network functioning.
resultsIn layer VI of normal-appearing MS cortex, excitatory and inhibitory synaptic densities were significantly lower than controls (reductions up to 14.9%), but demyelinated cortex showed larger losses of inhibitory synapses (29%). In our computational model, reducing inhibitory synapses impacted the network most, leading to a disinhibitory increase in neuronal activity and connectivity.
conclusionIn MS, excitatory and inhibitory synaptic losses were observed, predominantly for inhibitory synapses in demyelinated cortex. Inhibitory synaptic loss affected network functioning most, leading to increased neuronal activity and connectivity. As network disinhibition relates to cognitive impairment, inhibitory synaptic loss seems particularly relevant in MS.
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