ArticleMolecular brain2021
Simvastatin impairs hippocampal synaptic plasticity and cognitive function in mice.
Article in Molecular brain, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- The role of lipid metabolism in neuronal senescence.FEBS open bio · 2026Review
- Synergistic activity of simvastatin and irinotecan chemotherapy against glioblastoma converges on TGF-β signaling.Journal of neuro-oncology · 2025Article
- Endothelial delivery of simvastatin by LRP1-targeted nanoparticles ameliorates pathogenesis of alzheimer's disease in a mouse model.Alzheimer's research & therapy · 2025Article
- Cholesterol in the CNS: functions, recycling and remyelination.Journal of neuroinflammation · 2025Review
- Is Targeting LDL-C Levels Below 70 mg/dL Beneficial for Cardiovascular and Overall Health? A Critical Examination of the Evidence.Journal of clinical medicine · 2025Review
- Protective Effect of HMG-CoA Reductase Inhibitor Rosuvastatin on Doxorubicin-Induced Cognitive Impairment, Oxidative Stress and Neuroinflammation: Possible Role of CREB, ERK1/2, and BDNF.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Drug-Induced Cognitive Impairment.Drug safety · 2025Review
- Wnt3a/GSK3β/β-catenin Signalling Modulates Doxorubicin-associated Memory Deficits in Breast Cancer.Molecular neurobiology · 2024Article
- Simvastatin ameliorates synaptic plasticity impairment in chronic mild stress-induced depressed mice by modulating hippocampal NMDA receptor.Psychopharmacology · 2024Article
- Genetically instrumented LDL-cholesterol lowering and multiple disease outcomes: A Mendelian randomization phenome-wide association study in the UK Biobank.British journal of clinical pharmacology · 2023Article
- Review
- The role of IGF-1 in exercise to improve obesity-related cognitive dysfunction.Frontiers in neuroscience · 2023Review
- Review
- Cranial irradiation induces cognitive decline associated with altered dendritic spine morphology in the young rat hippocampus.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2022Article
- Importance of Coagulation Factors as Critical Components of Premature Cardiovascular Disease in Familial Hypercholesterolemia.International journal of molecular sciences · 2022Review
- Cardiovascular therapeutics: A new potential for anxiety treatment?Medicinal research reviews · 2022Review
- The role of DHCR24 in the pathogenesis of AD: re-cognition of the relationship between cholesterol and AD pathogenesis.Acta neuropathologica communications · 2022Review
- Statins and cognition: Modifying factors and possible underlying mechanisms.Frontiers in aging neuroscience · 2022Review
- Article
- Hypothesis: Entrapment of lipoprotein particles in the brain causes Alzheimer's disease.Free neuropathology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipophilic statins which are blood brain barrier (BBB) permeable are speculated to affect the cholesterol synthesis and neural functions in the central nervous system. However, whether these statins can affect cholesterol levels and synaptic plasticity in hippocampus and the in vivo consequence remain unclear. Here, we report that long-term subcutaneous treatments of simvastatin significantly impair mouse hippocampal synaptic plasticity, reflected by the attenuated long-term potentiation of field excitatory postsynaptic potentials. The simvastatin administration causes a deficiency in recognition and spatial memory but fails to affect motor ability and anxiety behaviors in the mice. Mass spectrometry imaging indicates a significant decrease in cholesterol intensity in hippocampus of the mice receiving chronic simvastatin treatments. Such effects of simvastatin are transient because drug discontinuation can restore the hippocampal cholesterol level and synaptic plasticity and the memory function. These findings may provide further clues to elucidate the mechanisms of neurological side effects, especially the brain cognitive function impairment, caused by long-term usage of BBB-permeable statins.
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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.