ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
Targeted rescue of synaptic plasticity improves cognitive decline in sepsis-associated encephalopathy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.
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Who cites it
15 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Global research trends and hotspots of short-chain fatty acids in cognitive impairment: a bibliometric analysis based on two databases.Frontiers in medicine · 2026Pooled it
- The core role of central nervous system in sepsis-related organ damage.Frontiers in immunology · 2025Pooled it
- In Situ Photo‑Crosslinked Functional Bilayer Hydrogel Modulates Local Microenvironment and Remyelination After Optic Nerve Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Hippocampal cytopathology orchestrates post-septic cognitive dysfunction.Metabolic brain disease · 2026Review
- Impact of Chronic Mild Stress on Neurotrophic and Hypothalamic-Pituitary-Adrenal Factors in the Brain of Rats Submitted to Sepsis.Neurotoxicity research · 2026Article
- Reversible synaptic deficits in early-stage batten disease.Journal of translational medicine · 2026Article
- HLA DP/DRA molecule regulates systemic inflammation and neuroinflammation, aggravates cognitive impairment and long-term anxiety in murine model of sepsis-associated encephalopathy.Frontiers in immunology · 2026Article
- Comparative Hippocampal Transcriptomics Reveals Model-Specific Pathways and Convergent Inflammation in Sepsis-Associated Encephalopathy.Neuromolecular medicine · 2025Article
- IRF7 drives macrophages to kill bacteria and improves septic outcomes via autophagy.JCI insight · 2025Article
- OTUD1 exacerbates sepsis-associated encephalopathy by promoting HK2 mitochondrial release to drive microglia pyroptosis.Journal of neuroinflammation · 2025Article
- Optimized Mouse Model of Sepsis-Associated Encephalopathy: A Rational Standard Based on Modified SHIRPA Score and Neurobehaviors in Mice.CNS neuroscience & therapeutics · 2025Article
- Microglia efferocytosis: an emerging mechanism for the resolution of neuroinflammation in Alzheimer's disease.Journal of neuroinflammation · 2025Review
- Targeting synaptic plasticity to bridge translational gaps in sepsis-associated encephalopathy.Frontiers in aging neuroscience · 2025Review
- Sepsis-associated encephalopathy: Mechanisms, Diagnosis, and Treatments update.International journal of biological sciences · 2025Review
- Prolactin deficiency drives diabetes-associated cognitive dysfunction by inducing microglia-mediated synaptic loss.Journal of neuroinflammation · 2024Article
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Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sepsis-associated encephalopathy (SAE) is a frequent complication of severe systemic infection resulting in delirium, premature death, and long-term cognitive impairment. We closely mimicked SAE in a murine peritoneal contamination and infection (PCI) model. We found long-lasting synaptic pathology in the hippocampus including defective long-term synaptic plasticity, reduction of mature neuronal dendritic spines, and severely affected excitatory neurotransmission. Genes related to synaptic signaling, including the gene for activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) and members of the transcription-regulatory EGR gene family, were downregulated. At the protein level, ARC expression and mitogen-activated protein kinase signaling in the brain were affected. For targeted rescue we used adeno-associated virus-mediated overexpression of ARC in the hippocampus in vivo. This recovered defective synaptic plasticity and improved memory dysfunction. Using the enriched environment paradigm as a non-invasive rescue intervention, we found improvement of defective long-term potentiation, memory, and anxiety. The beneficial effects of an enriched environment were accompanied by an increase in brain-derived neurotrophic factor (BDNF) and ARC expression in the hippocampus, suggesting that activation of the BDNF-TrkB pathway leads to restoration of the PCI-induced reduction of ARC. Collectively, our findings identify synaptic pathomechanisms underlying SAE and provide a conceptual approach to target SAE-induced synaptic dysfunction with potential therapeutic applications to patients with SAE.
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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.