Modulation of microglia activation by the ascorbic acid transporter SVCT2 DOI Creative Commons

Amanda Marino,

Tonia S. Rex, Fiona E. Harrison

et al.

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 120, P. 557 - 570

Published: July 6, 2024

Neuroinflammation is a major characteristic of pathology in several neurodegenerative diseases. Microglia, the brain's resident myeloid cells, shift between activation states under neuroinflammatory conditions, both responding to, but also driving damage brain. Vitamin C (ascorbate) an essential antioxidant for central nervous system function that may have specific role response. Uptake ascorbate throughout facilitated by sodium-dependent vitamin transporter 2 (SVCT2). SVCT2 transports reduced form into neurons and microglia, however contribution altered expression to response microglia not well understood. In this study we demonstrate modifies microglial response, as shown through changes cell morphology mRNA expression, following mild traumatic brain injury (mTBI) mice with decreased or increased SVCT2. Results were supported vitro studies immortalized line primary cultures derived from SVCT2-heterozygous transgenic animals. Overall, work demonstrates importance modulating mTBI suggests potential challenges.

Language: Английский

MOF-derived high-density carbon nanotubes “tentacle” with boosting electrocatalytic activity for detecting ascorbic acid DOI
Yan Zhang, Minghui Han,

Danni Peng

et al.

Talanta, Journal Year: 2024, Volume and Issue: 279, P. 126578 - 126578

Published: July 19, 2024

Language: Английский

Citations

8
Glioprotective Effects of Resveratrol Against Glutamate-Induced Cellular Dysfunction: The Role of Heme Oxygenase 1 Pathway DOI
André Quincozes‐Santos, Larissa Daniele Bobermin, Ana Carolina Tramontina

et al.

Neurotoxicity Research, Journal Year: 2025, Volume and Issue: 43(1)

Published: Jan. 27, 2025

Language: Английский

Citations

0
Trojan Horse Delivery Strategies of Natural Medicine Monomers: Challenges and Limitations in Improving Brain Targeting DOI Creative Commons

Kelu Lei,

Lanyu Zhou,

M. Bostenaru Dan

et al.

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(3), P. 280 - 280

Published: Feb. 20, 2025

Central nervous system (CNS) diseases, such as brain tumors, Alzheimer’s disease, and Parkinson’s significantly impact patients’ quality of life impose substantial economic burdens on society. The blood–brain barrier (BBB) limits the effective delivery most therapeutic drugs, especially natural products, despite their potential effects. Trojan Horse strategy, using nanotechnology to disguise drugs “cargo”, enables them bypass BBB, enhancing targeting efficacy. This review explores applications products in treatment CNS discusses challenges posed by analyzes advantages limitations strategy. Despite existing technical challenges, future research is expected enhance application integrating nanotechnology, improving mechanisms, optimizing characteristics.

Language: Английский

Citations

0
Vitamin C Modulates the PI3K/AKT Pathway via Glutamate and Nitric Oxide in Developing Avian Retina Cells in Culture DOI Creative Commons
Aline Teixeira Duarte-Silva, Ivan Domith,

Isabele Gonçalves-da-Silva

et al.

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(4), P. 369 - 369

Published: April 2, 2025

Background: In addition to its known antioxidant function, the reduced form of vitamin C, ascorbate, also acts as a neuromodulator in nervous system. Previous work showed reciprocal interaction ascorbate with glutamate chicken embryo retinal cultures. Ascorbate modulates extracellular levels by inhibiting excitatory amino acid transporter 3 and promoting activation NMDA receptors consequent intracellular signaling pathways involved transcription survival. Objective: present work, we investigated regulation AKT phosphorylation retina Methodology: Cultures cells were tested using Western blot, immunocytochemistry, fluorescent probe transfection, cellular imaging techniques. Results: Our results show that induces concentration time-dependent increase via accumulation glutamate, receptors, PI3K pathway. produces an calcium and, accordingly, is blocked chelator BAPTA-AM. Moreover, nitric oxide synthase inhibitor 7-nitroindazole, indicating it mediated oxide-dependent mechanisms. Conclusions: We demonstrate PI3K/AKT pathway cultures through NO production calcium-dependent manner. Given previous research has shown release cultures, our findings emphasize significance interactions between development. These provide further evidence supporting role

Language: Английский

Citations

0
Sex and organ specific proteomic responses to vitamin C deficiency in the brain, heart, liver, and spleen of Gulo-/- mice DOI Creative Commons
Lucie Aumailley, Michel Lebel

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(10), P. e0311857 - e0311857

Published: Oct. 10, 2024

Recent advances in mass spectrometry have indicated that the water-soluble antioxidant vitamin C differentially modulates abundance of various proteins hepatic tissue female and male mice. In this study, we performed LC-MS/MS to identify quantify correlate with serum concentrations whole brain, heart, liver, spleen tissues mice deficient for enzyme L-Gulonolactone oxidase required synthesis mammals. This work shows first time biological processes affected by a deficiency are not only sex specific dependent but also even though many been identified quantified more than three organs. For example, several complex III subunits mitochondrial electron transport chain correlated positively levels liver other examined study such were all organs analyzed. Western blot analyses on Uqcrc1 Uqcrfs1 validated results. Interestingly, ferritin represented few protein complexes examined. Concomitantly, light 1 was inversely serum. Thus, our provides an initial comprehensive atlas significantly correlating four will be useful resource scientific community.

Language: Английский

Citations

1
Increasing the vitamin C transporter SVCT2 in microglia improves synaptic plasticity and restrains memory impairments in Alzheimer’s disease models DOI Creative Commons
Camila C. Portugal, Evelyn Cristina da Silva Santos,

Ana M. Pacheco

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 4, 2024

Abstract Alzheimer’s Disease (AD) is characterized by progressive cognitive decline and synaptic dysfunction, often associated with amyloid-beta accumulation microglial alterations. Here, we investigate the role of Sodium-dependent Vitamin C Transporter 2 (SVCT2) in microglia to modulate AD-like pathology mice. Using a combination RNA sequencing, advanced quantitative proteomics, electrophysiology, behavioral tests, high-throughput imaging, viral gene delivery, explore interplay between SVCT2 expression microglia, load, proteome changes, plasticity. Our results demonstrate that decreases age 5xFAD mice, correlating memory deficits alterations mitochondrial proteome. Importantly, overexpression leads enhanced clearance amyloid plaques reconfiguration landscape synapses, improving long-term plasticity (LTP) performance. findings underscore as potent strategy simultaneously decrease enhance performance, offering new avenues for therapeutic interventions AD.

Language: Английский

Citations

0
Modulation of microglia activation by the ascorbic acid transporter SVCT2 DOI Creative Commons

Amanda Marino,

Tonia S. Rex, Fiona E. Harrison

et al.

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 120, P. 557 - 570

Published: July 6, 2024

Neuroinflammation is a major characteristic of pathology in several neurodegenerative diseases. Microglia, the brain's resident myeloid cells, shift between activation states under neuroinflammatory conditions, both responding to, but also driving damage brain. Vitamin C (ascorbate) an essential antioxidant for central nervous system function that may have specific role response. Uptake ascorbate throughout facilitated by sodium-dependent vitamin transporter 2 (SVCT2). SVCT2 transports reduced form into neurons and microglia, however contribution altered expression to response microglia not well understood. In this study we demonstrate modifies microglial response, as shown through changes cell morphology mRNA expression, following mild traumatic brain injury (mTBI) mice with decreased or increased SVCT2. Results were supported vitro studies immortalized line primary cultures derived from SVCT2-heterozygous transgenic animals. Overall, work demonstrates importance modulating mTBI suggests potential challenges.

Language: Английский

Citations

0