ArticleMolecular and cellular biochemistry2012
Homocysteine alters cerebral microvascular integrity and causes remodeling by antagonizing GABA-A receptor.
Article in Molecular and cellular biochemistry, 2012. 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, 34 citations in OpenAlex.
- Diet-Induced Hyperhomocysteinemia in C57BL/6 Mice: Simultaneous Evaluation of Plasma Homocysteine, Methionine, and Cysteine by LC-MS/MS and Assessment of Associated Oxidative Stress in Brain Homogenates.Antioxidants (Basel, Switzerland) · 2026Article
- Visual Hallucinations and Cognitive Impairment as the Initial Presentation of Severe Hypothyroidism in an Elderly Patient: A Case Report.Geriatrics (Basel, Switzerland) · 2026Article
- The Extracellular Matrix and the Immune System in Acute Lung Injury: Partners in Damage and Repair.Biomedicines · 2025Review
- Unraveling the nutritional challenges in epilepsy: Risks, deficiencies, and management strategies: A systematic review.World journal of experimental medicine · 2025Article
- The involvement of the synaptic vesicle cycle in homocysteine induced neurotoxicity in vitro and in vivo.Scientific reports · 2025Article
- Epigenetics of Homocystinuria, Hydrogen Sulfide, and Circadian Clock Ablation in Cardiovascular-Renal Disease.Current issues in molecular biology · 2024Review
- Lactobacillus Eats Amyloid Plaque and Post-Biotically Attenuates Senescence Due to Repeat Expansion Disorder and Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2024Article
- Targeting Glutamate Neurotoxicity through Dietary Manipulation: Potential Treatment for Migraine.Nutrients · 2023Review
- Microvascular Contributions to Alzheimer Disease Pathogenesis: Is Alzheimer Disease Primarily an Endotheliopathy?Biomolecules · 2023Review
- Homocysteine-Potential Novel Diagnostic Indicator of Health and Disease in Horses.Animals : an open access journal from MDPI · 2023Review
- Effect of hyperbaric oxygen combined with folic acid on clinical efficacy and cognitive function in patients with cerebral small vessel disease.American journal of translational research · 2023Article
- Exploring the complexities of 1C metabolism: implications in aging and neurodegenerative diseases.Frontiers in aging neuroscience · 2023Review
- GABAergic dysfunction, neural network hyperactivity and memory impairments in human aging and Alzheimer's disease.Seminars in cell & developmental biology · 2021Review
- Effect of donepezil on Hcy level in serum of Alzheimer's disease patients and correlation analysis of Hcy and dyssomnia.Experimental and therapeutic medicine · 2019Article
- Hydrogen Sulfide Ameliorates Homocysteine-Induced Alzheimer's Disease-Like Pathology, Blood-Brain Barrier Disruption, and Synaptic Disorder.Molecular neurobiology · 2016Article
- Genetic Influences on Plasma Homocysteine Levels in African Americans and Yoruba Nigerians.Journal of Alzheimer's disease : JAD · 2016Article
- Ablation of MMP9 gene ameliorates paracellular permeability and fibrinogen-amyloid beta complex formation during hyperhomocysteinemia.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2014Article
- MMP-9 gene ablation mitigates hyperhomocystenemia-induced cognition and hearing dysfunction.Molecular biology reports · 2014Article
- One-carbon cycle alterations induced by Dyrk1a dosage.Molecular genetics and metabolism reports · 2014Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
High levels of homocysteine (Hcy), known as hyperhomocysteinemia (HHcy), are associated with cerebrovascular diseases, such as vascular dementia, stroke, and Alzheimer's disease. The γ-amino butyric acid (GABA) is an inhibitory neurotransmitter and a ligand of GABA-A receptor. By inhibiting excitatory response, it may decrease complications associated with vascular dementia and stroke. Hcy specifically competes with the GABA-A receptors and acts as an excitotoxic neurotransmitter. Previously, we have shown that Hcy increases levels of NADPH oxidase and reactive oxygen species (ROS), and decreases levels of thioredoxin and peroxiredoxin by antagonizing the GABA-A receptor. Hcy treatment leads to activation of matrix metalloproteinases (MMPs) in cerebral circulation by inducing redox stress and ROS. The hypothesis is that Hcy induces MMPs and suppresses tissue inhibitors of metalloproteinase (TIMPs), in part, by inhibiting the GABA-A receptor. This leads to degradation of the matrix and disruption of the blood brain barrier. The brain cortex of transgenic mouse model of HHcy (cystathionine β-synthase, CBS-/+) and GABA-A receptor null mice treated with and without muscimol (GABA-A receptor agonist) was analysed. The mRNA levels were measured by Q-RT-PCR. Levels of MMP-2, -9, -13, and TIMP-1, -2, -3, and -4 were evaluated by in situ labeling and PCR-gene arrays. Pial venular permeability to fluorescence-labeled albumin was assessed with intravital fluorescence microscopy. We found that Hcy increases metalloproteinase activity and decreases TIMP-4 by antagonizing the GABA-A receptor. The results demonstrate a novel mechanism in which brain microvascular permeability changes during HHcy and vascular dementias, and have therapeutic ramifications for microvascular disease in Alzheimer's patients.
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