ArticleActa neuropathologica2021
Complement-associated loss of CA2 inhibitory synapses in the demyelinated hippocampus impairs memory.
Article in Acta neuropathologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 58 citations in OpenAlex.
- Immune-mediated excitotoxicity in brain disorders.Nature reviews. Immunology · 2026Review
- Increased Ih Current Is Associated with Reduced Hippocampal CA1 Excitability in a Mouse Model of Multiple Sclerosis.eNeuro · 2026Article
- FreeSurfer-Based MRI Volumetry Reveals Thalamic and Hippocampal Atrophy as Significant Correlates of Disability in Multiple Sclerosis.Medicina (Kaunas, Lithuania) · 2026Article
- Autoradiographic assessment of SynVesT-1 revealed changes in non-displaceable binding with demyelination and remyelination: implications for SV2A PET analysis.EJNMMI research · 2026Article
- Demyelination-induced glutamatergic imbalance mediates hippocampal Hyperexcitability.Neurobiology of disease · 2025Article
- Modeling neurodegeneration in the retina and strategies for developing pan-neurodegenerative therapies.Molecular neurodegeneration · 2025Review
- A focus on the normal-appearing white and gray matter within the multiple sclerosis brain: a link to smoldering progression.Acta neuropathologica · 2025Review
- Review
- Multiple sclerosis: what have we learned and can we still learn from electron microscopy.Cellular and molecular life sciences : CMLS · 2025Review
- Astrocyte-derived complement C3 facilitated microglial phagocytosis of synapses in Staphylococcus aureus-associated neurocognitive deficits.PLoS pathogens · 2025Article
- Astroglial modulation of synaptic function in the non-demyelinated cerebellar cortex is dependent on MyD88 signaling in a model of toxic demyelination.Journal of neuroinflammation · 2025Article
- Incomplete remyelination via therapeutically enhanced oligodendrogenesis is sufficient to recover visual cortical function.Nature communications · 2025Article
- Lingo1 in the hippocampus contributes to cognitive dysfunction after anesthesia and surgery in aged mice.International journal of biological sciences · 2025Article
- Microglia and Immune cells interactions in multiple sclerosis cognitive impairment: a postmortem study.Journal of neuroinflammation · 2024Article
- Homonymous hemi-macular atrophy in multiple sclerosis.Multiple sclerosis (Houndmills, Basingstoke, England) · 2024Article
- VEP Latency Delay Reflects Demyelination Beyond the Optic Nerve in the Cuprizone Model.Investigative ophthalmology & visual science · 2024Article
- Immunity impacts cognitive deficits across neurological disorders.Journal of neurochemistry · 2024Review
- Instability of excitatory synapses in experimental autoimmune encephalomyelitis and the outcome for excitatory circuit inputs to individual cortical neurons.Brain, behavior, and immunity · 2024Article
- Pilot Study of the Total and Phosphorylated Tau Proteins in Early-Stage Multiple Sclerosis.Medicina (Kaunas, Lithuania) · 2024Article
- Hotspots and trends of microglia in Alzheimer's disease: a bibliometric analysis during 2000-2022.European journal of medical research · 2024Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The complement system is implicated in synapse loss in the MS hippocampus, but the functional consequences of synapse loss remain poorly understood. Here, in post-mortem MS hippocampi with demyelination we find that deposits of the complement component C1q are enriched in the CA2 subfield, are linked to loss of inhibitory synapses and are significantly higher in MS patients with cognitive impairments compared to those with preserved cognitive functions. Using the cuprizone mouse model of demyelination, we corroborated that C1q deposits are highest within the demyelinated dorsal hippocampal CA2 pyramidal layer and co-localized with inhibitory synapses engulfed by microglia/macrophages. In agreement with the loss of inhibitory perisomatic synapses, we found that Schaffer collateral feedforward inhibition but not excitation was impaired in CA2 pyramidal neurons and accompanied by intrinsic changes and a reduced spike output. Finally, consistent with excitability deficits, we show that cuprizone-treated mice exhibit impaired encoding of social memories. Together, our findings identify CA2 as a critical circuit in demyelinated intrahippocampal lesions and memory dysfunctions in MS.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.