ArticleMolecular psychiatry2021
A CRHR1 antagonist prevents synaptic loss and memory deficits in a trauma-induced delirium-like syndrome.
Article in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Detailed stratified GWAS analysis for severe COVID-19 in four European populations.Human molecular genetics · 2022Pooled it
- Loss of C3 and CD14 reduces region-specific neuroinflammation in a murine polytrauma model.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- The NMDAR/TRPM4 death complex is a major promoter of disease progression in the 5xFAD mouse model of Alzheimer's disease.Molecular psychiatry · 2026Article
- Targeted Proteomics upon Treatment with Tofersen Identifies Novel Response Markers for Superoxide Dismutase 1-Linked Amyotrophic Lateral Sclerosis.Annals of neurology · 2025Article
- Genetically supported targets and drug repurposing for brain aging: A systematic study in the UK Biobank.Science advances · 2025Article
- Targeting corticotropin-releasing hormone receptor type 1 (Crhr1) neurons: validating the specificity of a novel transgenic Crhr1-FlpO mouse.Brain structure & function · 2024Article
- Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries.Nature genetics · 2024Article
- Mapping the epigenomic landscape of post-traumatic stress disorder in human cortical neurons.medRxiv : the preprint server for health sciences · 2024Article
- Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries.medRxiv : the preprint server for health sciences · 2024Article
- Chronic stress induces Alzheimer's disease-like pathologies through DNA damage-Chk1-CIP2A signaling.Aging · 2024Article
- Liraglutide ameliorates delirium-like behaviors of aged mice undergoing cardiac surgery by mitigating microglia activation via promoting mitophagy.Psychopharmacology · 2024Article
- Increased A1 astrocyte activation-driven hippocampal neural network abnormality mediates delirium-like behavior in aged mice undergoing cardiac surgery.Aging cell · 2024Article
- Scopolamine causes delirium-like brain network dysfunction and reversible cognitive impairment without neuronal loss.Zoological research · 2023Article
- Three-dimensional chromatin architecture datasets for aging and Alzheimer's disease.Scientific data · 2023Article
- Article
- Shank2/3 double knockout-based screening of cortical subregions links the retrosplenial area to the loss of social memory in autism spectrum disorders.Molecular psychiatry · 2022Article
- E4BP4 Coordinates Circadian Control of Cognition in Delirium.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- BDNF Therapeutic Mechanisms in Neuropsychiatric Disorders.International journal of molecular sciences · 2022Review
- Deletion of the Autism-Associated Protein SHANK3 Abolishes Structural Synaptic Plasticity after Brain Trauma.International journal of molecular sciences · 2022Article
- Corticotropin-releasing hormone (CRH) alters mitochondrial morphology and function by activating the NF-kB-DRP1 axis in hippocampal neurons.Cell death & disease · 2020Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Older patients with severe physical trauma are at high risk of developing neuropsychiatric syndromes with global impairment of cognition, attention, and consciousness. We employed a thoracic trauma (TxT) mouse model and thoroughly analyzed age-dependent spatial and temporal posttraumatic alterations in the central nervous system. Up to 5 days after trauma, we observed a transient 50% decrease in the number of excitatory synapses specifically in hippocampal pyramidal neurons accompanied by alterations in attention and motor activity and disruption of contextual memory consolidation. In parallel, hippocampal corticotropin-releasing hormone (CRH) expression was highly upregulated, and brain-derived neurotrophic factor (BDNF) levels were significantly reduced. In vitro experiments revealed that CRH application induced neuronal autophagy with rapid lysosomal degradation of BDNF via the NF-κB pathway. The subsequent synaptic loss was rescued by BDNF as well as by specific NF-κB and CRH receptor 1 (CRHR1) antagonists. In vivo, the chronic application of a CRHR1 antagonist after TxT resulted in reversal of the observed histological, molecular, and behavioral alterations. The data suggest that neuropsychiatric syndromes (i.e., delirium) after peripheral trauma might be at least in part due to the activation of the hippocampal CRH/NF-κB/BDNF pathway, which results in a dramatic loss of synaptic contacts. The successful rescue by stress hormone receptor antagonists should encourage clinical trials focusing on trauma-induced delirium and/or other posttraumatic syndromes.
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