ArticleNeuroscience bulletin2022
Homocysteine-Induced Disturbances in DNA Methylation Contribute to Development of Stress-Associated Cognitive Decline in Rats.
Article in Neuroscience bulletin, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Molecular insights into enriched environments and behavioral improvements in autism: a systematic review and meta-analysis.Frontiers in psychiatry · 2024Pooled it
- Cystathionine β-synthase is inhibited by epinephrine and norepinephrine over-secretion via NF-κB activation in stress-induced hyperhomocysteinemia.Scientific reports · 2026Article
- Homocysteine Drives Hippocampal Blood-Brain Barrier Disruption and Cognitive Decline Under Chronic Stress via DNA Hypomethylation of Cav1.2.Brain sciences · 2026Article
- Review
- High-intensity interval training improves cognitive dysfunction in chronically stressed mice through alleviating homocysteine-induced transcriptional repression ofNeurobiology of stress · 2025Article
- Oral-Gut Microbiota Crosstalk and Epigenetic Targets in Metabolic and Neuropsychiatric Diseases.Nutrients · 2025Review
- The Role of Prenatal Microglial Activation and Its Sex Differences in the Development of Neuropsychiatric Disorders and Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Homocysteine Mediates Cognitive Inflexibility Induced by Stress via Targeting PIN1.Brain sciences · 2025Article
- Rutin ameliorates stress-induced blood‒brain barrier dysfunction and cognitive decline via the endothelial HDAC1‒Claudin-5 axis.Fluids and barriers of the CNS · 2025Article
- Homocysteine, HHcy, H-type hypertension and dizziness: an NHANES analysis.Frontiers in neurology · 2025Article
- Inhibition of Glycolysis Alleviates Chronic Unpredictable Mild Stress Induced Neuroinflammation and Depression-like Behavior.Brain sciences · 2024Article
- Positive association between increased homocysteine and deficit syndrome in Chinese patients with chronic schizophrenia: a large-scale cross-sectional study.European archives of psychiatry and clinical neuroscience · 2024Article
- Chronic stress induces Alzheimer's disease-like pathologies through DNA damage-Chk1-CIP2A signaling.Aging · 2024Article
- GLUT1-mediated microglial proinflammatory activation contributes to the development of stress-induced spatial learning and memory dysfunction in mice.Cell & bioscience · 2024Article
- Serum interleukin-17 A and homocysteine levels in children with autism.BMC neuroscience · 2024Article
- Betaine alleviates cognitive impairment induced by homocysteine through attenuating NLRP3-mediated microglial pyroptosis in an mRedox biology · 2024Article
- DNMT1 involved in the analgesic effect of folic acid on gastric hypersensitivity through downregulating ASIC1 in adult offspring rats with prenatal maternal stress.CNS neuroscience & therapeutics · 2023Article
- Review
- Homocysteine accelerates hepatocyte autophagy by upregulating TFEB via DNMT3b-mediated DNA hypomethylation.Acta biochimica et biophysica Sinica · 2023Article
- Maternal genetic polymorphisms in the major mitotic checkpoint genesFrontiers in genetics · 2023Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic stress is generally accepted as the main risk factor in the development of cognitive decline; however, the underlying mechanisms remain unclear. Previous data have demonstrated that the levels of homocysteine (Hcy) are significantly elevated in the plasma of stressed animals, which suggests that Hcy is associated with stress and cognitive decline. To test this hypothesis, we analyzed the cognitive function, plasma concentrations of Hcy, and brain-derived neurotropic factor (BDNF) levels in rats undergoing chronic unpredicted mild stress (CUMS). The results showed that decreased cognitive behavioral performance and decreased BDNF transcription and protein expression were correlated with hyperhomocysteinemia (HHcy) levels in stressed rats. Diet-induced HHcy mimicked the cognitive decline and BDNF downregulation in the same manner as CUMS, while Hcy reduction (by means of vitamin B complex supplements) alleviated the cognitive deficits and BDNF reduction in CUMS rats. Furthermore, we also found that both stress and HHcy disturbed the DNA methylation process in the brain and induced DNA hypermethylation in the BDNF promoter. In contrast, control of Hcy blocked BDNF promoter methylation and upregulated BDNF levels in the brain. These results imply the possibility of a causal role of Hcy in stress-induced cognitive decline. We also used ten-eleven translocation (TET1), an enzyme that induces DNA demethylation, to verify the involvement of Hcy and DNA methylation in the regulation of BDNF expression and the development of stress-related cognitive decline. The data showed that TET1-expressing viral injection into the hippocampus inhibited BDNF promoter methylation and significantly mitigated the cognitive decline in HHcy rats. Taken together, novel evidence from the present study suggests that Hcy is likely involved in chronic stress-induced BDNF reduction and related cognitive deficits. In addition, the negative side-effects of HHcy may be associated with Hcy-induced DNA hypermethylation in the BDNF promoter. The results also suggest the possibility of Hcy as a target for therapy and the potential value of vitamin B intake in preventing stress-induced cognitive decline.
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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 Socratic graph.