ArticleLipids in health and disease2014
LDL receptor knock-out mice show impaired spatial cognition with hippocampal vulnerability to apoptosis and deficits in synapses.
Article in Lipids in health and disease, 2014. 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, 42 citations in OpenAlex.
- Dyslipidemia-Induced Mitochondrial Dysfunctions in the Brains Does Not Reach Pathological Levels in the ApoE-Knockout Mice.Neurochemical research · 2026Article
- Sex- and age-dependent mitochondrial dysfunction and cognitive impairment in a mouse model of familial hypercholesterolemia.Biology of sex differences · 2026Article
- Navigating the cholesterol maze: Key insights on use of statins in neurodegenerative disorders.Neuroprotection (Chichester, England) · 2026Review
- Sex Differences on Social and Anxiety-Related Responses in Low-Density Lipoprotein Receptor Knockout Mice.Molecular neurobiology · 2026Article
- Article
- Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Alzheimer's Disease: Recent Advances and Controversies.Molecular neurobiology · 2025Review
- The Emerging Role of PCSK9 in the Pathogenesis of Alzheimer's Disease: A Possible Target for the Disease Treatment.International journal of molecular sciences · 2024Review
- Carbon Nanodots Attenuate Lipid Peroxidation in the LDL Receptor Knockout Mouse Brain.Antioxidants (Basel, Switzerland) · 2023Article
- Impaired Cholesterol Metabolism, Neurons, and Neuropsychiatric Disorders.Experimental neurobiology · 2023Review
- Emerging Epidemiological Data on Rare Intellectual Disability Syndromes from Analyzing the Data of a Large Iranian Cohort.Archives of Iranian medicine · 2023Article
- Focused ultrasound mitigates pathology and improves spatial memory in Alzheimer's mice and patients.Theranostics · 2023Article
- Oxidative Stress and Lipid Accumulation Augments Cell Death in LDLR-Deficient RPE Cells andCells · 2022Article
- Free Triiodothyronine Levels are Related to Executive Function and Scene Memory in Type 2 Diabetes Mellitus Patients Without Diagnosed Thyroid Diseases.Diabetes, metabolic syndrome and obesity : targets and therapy · 2022Article
- Inverted U-shaped correlation between serum low-density lipoprotein cholesterol levels and cognitive functions of patients with type 2 diabetes mellitus.Lipids in health and disease · 2021Article
- The CC Genotype ofBioMed research international · 2020Article
- Cerebrovascular Changes and Neurodegeneration Related to Hyperlipidemia: Characteristics of the Human ApoB-100 Transgenic Mice.Current pharmaceutical design · 2020Article
- mTOR drives cerebrovascular, synaptic, and cognitive dysfunction in normative aging.Aging cell · 2020Article
- Elevated tumor LDLR expression accelerates LDL cholesterol-mediated breast cancer growth in mouse models of hyperlipidemia.Oncogene · 2017Article
- Ratio of apoB/LDL: a potential clinical index for vascular cognitive impairment.BMC neurology · 2016Article
- Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial.Frontiers in aging neuroscience · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEvidence from clinical studies support the fact that abnormal cholesterol metabolism in the brain leads to progressive cognitive dysfunction. The low-density lipoprotein receptor (LDLR) is well-known for its role in regulating cholesterol metabolism. Whether LDLR involved in this impaired cognition and the potential mechanisms that underlie this impairment are unknown.
methodsTwelve-month-old Ldlr-/- mice (n = 10) and wild-type littermates C57BL/6 J (n = 14) were subjected to the Morris water maze test. At 1 week after completion of the behavioural testing, all of the animals were sacrificed for analysis of synaptic and apoptotic markers.
resultsThe plasma cholesterol concentration of Ldlr-/- mice was increased moderately when compared with C57BL/6 J mice (P < 0.05). Behavioural testing revealed that Ldlr-/- mice displayed impaired spatial memory, and moreover, the expression levels of synaptophysin and the number of synaptophysin-immunoreactive presynaptic boutons in the hippocampal CA1 and dentate gyrus were decreased (all P < 0.05). Ultrastructural changes in the dentate gyrus were observed using transmission electron microscopy. Furthermore, apoptosis in the hippocampus of Ldlr-/- mice was revealed based on elevation, at both the mRNA and protein levels, of the ratio of Bax/Bcl-2 expression (all P < 0.05)and an increase in activated-caspase3 protein level (P < 0.05).
conclusionLDLR deficiency contributes to impaired spatial cognition. This most likely occurs via negative effects that promote apoptosis and synaptic deficits in the hippocampus.
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