Similar Datasets
Project description:Chronic stress is a major risk factor for cognitive decline and blood-brain barrier (BBB) disruption, yet the underlying molecular mechanisms remain elusive. This study aimed to investigate the specific role of the metabolic intermediate homocysteine (Hcy) in chronic stress-induced BBB dysfunction and cognitive impairment. Methods: We utilized a rat model of chronic unpredictable mild stress (CUMS) and administered Vitamin B complex to lower Hcy levels in vivo. Regional Hcy accumulation, BBB permeability, and cognitive behaviors were assessed. In vitro, primary rat brain microvascular endothelial cells (BMECs) were exposed to Hcy to evaluate barrier-forming function, transcriptomic alterations, DNA methylation patterns, Cav1.2 expression, and reactive oxygen species (ROS) production. Results: CUMS selectively induced BBB hyperpermeability and significant Hcy accumulation predominantly within the rat hippocampus, which correlated intimately with cognitive deficits. Lowering Hcy levels via Vitamin B supplementation successfully restored hippocampal BBB integrity and alleviated cognitive impairment. In addition, elevated Hcy severely impaired the barrier function of BMECs. Mechanistically, Hcy reduced global DNA methylation in BMECs and specifically induced targeted DNA hypomethylation at the intro region of Cacna1c. This epigenetic shift caused the transcriptional derepression and overexpression of the Cav1.2 calcium channel. Upregulated Cav1.2 subsequently triggered a robust ROS burst, leading to tight junction degradation. Conclusions: Our findings unveil a novel metabolic-epigenetic axis where Hcy-driven Cacna1c hypomethylation directly disrupts BMEC function to dismantle the hippocampal BBB. Lowering Hcy or targeting this Hcy-Cav1.2 pathway establishes a promising therapeutic strategy for mitigating stress-related neurovascular damage and cognitive disorders.
2026-06-03 | GSE327662 | GEO
Project description:Chronic stress is a major risk factor for cognitive decline and blood-brain barrier (BBB) disruption, yet the underlying molecular mechanisms remain elusive. This study aimed to investigate the specific role of the metabolic intermediate homocysteine (Hcy) in chronic stress-induced BBB dysfunction and cognitive impairment. Methods: We utilized a rat model of chronic unpredictable mild stress (CUMS) and administered Vitamin B complex to lower Hcy levels in vivo. Regional Hcy accumulation, BBB permeability, and cognitive behaviors were assessed. In vitro, primary rat brain microvascular endothelial cells (BMECs) were exposed to Hcy to evaluate barrier-forming function, transcriptomic alterations, DNA methylation patterns, Cav1.2 expression, and reactive oxygen species (ROS) production. Results: CUMS selectively induced BBB hyperpermeability and significant Hcy accumulation predominantly within the rat hippocampus, which correlated intimately with cognitive deficits. Lowering Hcy levels via Vitamin B supplementation successfully restored hippocampal BBB integrity and alleviated cognitive impairment. In addition, elevated Hcy severely impaired the barrier function of BMECs. Mechanistically, Hcy reduced global DNA methylation in BMECs and specifically induced targeted DNA hypomethylation at the intro region of Cacna1c. This epigenetic shift caused the transcriptional derepression and overexpression of the Cav1.2 calcium channel. Upregulated Cav1.2 subsequently triggered a robust ROS burst, leading to tight junction degradation. Conclusions: Our findings unveil a novel metabolic-epigenetic axis where Hcy-driven Cacna1c hypomethylation directly disrupts BMEC function to dismantle the hippocampal BBB. Lowering Hcy or targeting this Hcy-Cav1.2 pathway establishes a promising therapeutic strategy for mitigating stress-related neurovascular damage and cognitive disorders.
2026-06-03 | GSE327052 | GEO
Project description:RNA-seq analysis of HTL and betaine-treated HT-22 cells
| PRJNA1331767 | ENA
Project description:PGC-1α overexpression in neurons protects against chronic cerebral hypoperfusion-induced cognitive impairment in mice. To investigate the neuroprotective mechanism of PGC-1α, we employed RNA-Seq analysis on PGC-1α-overexpressed HT-22 cells, a hippocampal neuron cell line. We performed OGD experiment to mimick chronic cerebral hypoperfusion. Indeed, PGC-1α overexpression alters the gene expression profiles of HT-22 cells, suggesting that neuronal PGC-1α might play an important role after chronic cerebral hypoperfusion.
2019-03-05 | GSE127788 | GEO
Project description:This study aims to examine the effects of betaine on the survival, proliferation, and invasion of human oral squamous carcinoma cells (HSC) and further elucidate the potential function of betaine via the utilisation of proteomic analysis.
2025-05-07 | PXD054595 | Pride
Project description:Proline betaine, and to a much lesser extent, N-methyl L-proline, are found in citrus fruits and often present in the human metabolome. However, most of the N-methyl L-proline found in an animal model metabolome is produced by the microbiota, yet organisms and enzymes capable of producing N-methyl proline in the anoxic intestine have been unknown. The anaerobe Eubacterium limosum ATCC 8486 makes acetate and butyrate from various substrates and is found in the human intestine. We found that this organism demethylates proline betaine and excretes N-methyl proline during growth. The proteome of proline betaine-grown Eubacterium limosum was obtained in order to identify enzymes required for growth on proline, in particular to identify components that are unique to growth on proline in comparison to other substrates for acetogenesis, such as lactic acid. Comparison of the proteomes of the bacteria on proline betaine and lactic acid led to identification of the proteins involved in a proline betaine:tetrahydrofolate methyltransferase system which was biochemically verified. The key proline betaine demethylating enzyme is a member of the widespread TMA methyltransferase protein superfamily.
2019-07-25 | PXD013962 | Pride
Project description:Purpose: Understanding the mechanism of action of lauryl betaine against Cryptococcus neoformans and Malassezia restricta. Methods: The transcriptome profile of the lauryl betaine-treated cells compared to that of untreated cells were generated by RNA-seq Illumina Hiseq. Results: A number of genes were differentially expressed in the lauryl betaine-treated cells, which include genes involved in ergosterol biosynthetic pathway.
2019-08-22 | GSE124734 | GEO
Project description:Betaine (trimethylglycine) is a non-toxic, highly water-soluble organic osmolyte widely used in skin care due to its assumed moisturizing and protective properties, but only few studies have addressed its specific effects in skin. Here, the cellular and molecular targets of betaine were analyzed by genome-wide expression analysis in organotypic cultures of rat epidermal keratinocytes (REK). In this model, we also examined whether betaine modifies the impacts of acute UVB exposure. The expression of several genes relevant to epidermal biology, proliferation/differentiation or malignancy as well as solute transport were verified by independent methods (qRT-PCR, western blotting). The data concerning changes in calcium metabolism after UVB exposure has been published separately (Bart et al., Br. J. Dermatol. 171:376-387, 2014). Organotypic cultures of rat epidermal keratinocytes (REK) were prepared by plating cells on a collagen-coated insert (submerged in medium), lifting the confluent cell layer to the air-liquid interface 3 days after plating. These 3D cultures were divided in four treatment groups with three replicates in each: control, betaine (10 mM), UVB (30 mJ/cm2) and betaine + UVB. Betaine was added to the cultures for 11 days, starting from day 4 until sample collection. UVB exposure was performed 24 h prior to sample collection for 2-week-old 3D cultures with a well-formed epidermal layer. For further details on the experimental set-up and characteristics of the UV source, please refer to Bart et al. (Br. J. Dermatol. 171:376-387, 2014) and Rauhala et al. (J. Biol. Chem. 288:17999-18012, 2013).
2015-10-26 | E-GEOD-63004 | biostudies-arrayexpress
Project description:In order to explore the effect of betaine on NAFLD and its mechanism, we divided mice into high-fat diet (HF) and high-fat diet with betaine (HB) groups, and used N6-methyladenosine sequence (m6A-seq), RNA-seq and mRNAs bound to ribosome-nascent chain complex sequencing (RNC-seq) to evaluate the gene expression levels in the liver of each group.
2021-05-20 | GSE174550 | GEO
Project description:An excessive high-fat/energy diet is a major cause of obesity and associated complications, such as non-alcoholic fatty liver disease (NAFLD). Betaine has been shown to effectively improve hepatic lipid metabolism. However, the mechanistic basis for this improvement is largely unknown. Herein, integration of transcriptomics sequencing (RNA-seq) and ribosome footprints profiling (Ribo-seq) was used to investigate the means by which betaine alleviates hepatic lipid metabolic disorders induced by a high-fat diet. For the transcriptome, gene set enrichment analysis demonstrated betaine to reduce liver steatosis by up-regulation of fatty acid beta oxidation, lipid oxidation, and fatty acid catabolic processes. For the translatome, 574 differentially expressed genes were identified, 17 of which were associated with the NAFLD pathway. By combined analysis of RNA-seq and Ribo-seq, we found that betaine had the greatest effect on NAFLD at the translational level. Further, betaine decreased translational efficiency (TE) for IDI1, CYP5A1, TM7SF2, and APOA4, which are related to lipid biosynthesis. In summary, this study demonstrates betaine to alleviate lipid metabolic dysfunction at the translational level. The powerful multi-omics data integration approach used herein provides for a new understanding of the means by which to treat NAFLD.
2021-07-31 | GSE181077 | GEO