ArticleThe Journal of clinical investigation2022
Sphingosine-1-phosphate receptor 1 activation in the central nervous system drives cisplatin-induced cognitive impairment.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 46 citations in OpenAlex.
- Changes in EEG Microstate Dynamics and Cognition Post-Chemotherapy in People With Breast Cancer.Brain and behavior · 2025Trial
- Constellations of Thought: Astrocytic Contributions to Cognition Across Rodent Models of Brain Dysfunction.Biomolecules · 2026Review
- Mechanistic insights and therapeutic interventions of mitochondrial quality control in chemotherapy-related cognitive impairment.Neoplasia (New York, N.Y.) · 2026Review
- A systematic review of the neurobiological mechanisms of chemotherapy-induced deficits in executive functions.Brain, behavior, & immunity - health · 2026Review
- Cisplatin-induced toxicity in the hippocampus: a dose-dependent mechanism of damage.BMC pharmacology & toxicology · 2025Article
- Daflon attenuates cisplatin-induced cerebellar neurotoxicity, anxiety-like behavior, and motor dysfunction by downregulating TLR4/NF-kB signaling.BMC pharmacology & toxicology · 2025Article
- Cognitive training for breast cancer patients with cancer-related cognitive impairment: a scoping review.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025Article
- Gut microbiota mediates semaglutide attenuation of diabetes-associated cognitive decline.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Decreased Expression and Secretion of the Myokine Fndc5/Irisin by Cisplatin Treatment in Mouse Skeletal Muscle.Calcified tissue international · 2025Article
- Sphingosine 1-phosphate receptor 1 modulators exert neuroprotective effects in central nervous system disorders.Frontiers in pharmacology · 2025Review
- Temporal dynamics of cisplatin-induced endothelial senescence and its association with cognitive impairment: insights into the medial prefrontal cortex.Frontiers in oncology · 2025Article
- Article
- Involvement of sphingosine-1-phosphate receptor 1 in pain insensitivity in a BTBR mouse model of autism spectrum disorder.BMC medicine · 2024Article
- From Immunity to Neurogenesis: Toll-like Receptors as Versatile Regulators in the Nervous System.International journal of molecular sciences · 2024Review
- Children with non-central nervous system tumors treated with platinum-based chemotherapy are at risk for hearing loss and cognitive impairments.Frontiers in pediatrics · 2024Article
- Air pollution accelerates the development of obesity and Alzheimer's disease: the role of leptin and inflammation - a mini-review.Frontiers in immunology · 2024Review
- Implications of immunometabolism for smouldering MS pathology and therapy.Nature reviews. Neurology · 2023Review
- [Mobile everyday-life digital technologies for the prevention of Alzheimer's dementia: cognitive health and cognitive safety].Der Nervenarzt · 2023Review
- Neuroimaging based biotypes for precision diagnosis and prognosis in cancer-related cognitive impairment.Frontiers in medicine · 2023Review
- Curcumin-loaded graphene oxide quantum dots enhance otoprotective effects via blocking cuproptosis.Frontiers in bioengineering and biotechnology · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Cancer-related cognitive impairment (CRCI) is a major neurotoxicity affecting more than 50% of cancer survivors. The underpinning mechanisms are mostly unknown, and there are no FDA-approved interventions. Sphingolipidomic analysis of mouse prefrontal cortex and hippocampus, key sites of cognitive function, revealed that cisplatin increased levels of the potent signaling molecule sphingosine-1-phosphate (S1P) and led to cognitive impairment. At the biochemical level, S1P induced mitochondrial dysfunction, activation of NOD-, LRR-, and pyrin domain-containing protein 3 inflammasomes, and increased IL-1β formation. These events were attenuated by systemic administration of the functional S1P receptor 1 (S1PR1) antagonist FTY720, which also attenuated cognitive impairment without adversely affecting locomotor activity. Similar attenuation was observed with ozanimod, another FDA-approved functional S1PR1 antagonist. Mice with astrocyte-specific deletion of S1pr1 lost their ability to respond to FTY720, implicating involvement of astrocytic S1PR1. Remarkably, our pharmacological and genetic approaches, coupled with computational modeling studies, revealed that cisplatin increased S1P production by activating TLR4. Collectively, our results identify the molecular mechanisms engaged by the S1P/S1PR1 axis in CRCI and establish S1PR1 antagonism as an approach to target CRCI with therapeutics that have fast-track clinical application.
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Registered trials
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.