Tracing the path of disruption: ¹³C isotope applications in traumatic brain injury‐induced metabolic dysfunction

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(3)

Published: March 1, 2024

Abstract Cerebral metabolic dysfunction is a critical pathological hallmark observed in the aftermath of traumatic brain injury (TBI), as extensively documented clinical investigations and experimental models. An in‐depth understanding bioenergetic disturbances that occur following TBI promises to reveal novel therapeutic targets, paving way for timely development interventions improve patient outcomes. The 13 C isotope tracing technique represents robust methodological advance, harnessing biochemical quantification delineate trajectories isotopically labeled substrates. This nuanced approach enables real‐time mapping fluxes, providing window into cellular energetic state elucidating perturbations key circuits. By applying this sophisticated tool, researchers can dissect complexities networks within central nervous system, offering insights derangements specific pathology. Embraced by both animal studies research, has bolstered our TBI‐induced dysregulation. review synthesizes current applications its transformative potential evaluating addressing sequelae TBI.

Language: Английский

---

Investigating Past, Present, and Future Trends on Interface Between Marine and Medical Research and Development: A Bibliometric Review

Marine Drugs, Journal Year: 2025, Volume and Issue: 23(1), P. 34 - 34

Published: Jan. 10, 2025

The convergence of marine sciences and medical studies has the potential for substantial advances in healthcare. This study uses bibliometric topic modeling to map progression research themes from 2000 2023, with an emphasis on interdisciplinary subject sciences. Building global publication output at interface between using Hierarchical Dirichlet Process, we discovered dominating topics during three periods, emphasizing shifts focus development trends. Our data show a significant rise output, indicating growing interest bioresources applications. paper identifies two main areas active research, "natural product biochemistry" "trace substance genetics", both great therapeutic potential. We used social network analysis collaborative networks identify prominent scholars institutions driving this progress. indicates important paths policy R&D management operating crossroads healthcare innovation It also underscores significance quantitative foresight methods teams identifying interpreting future scientific convergences breakthroughs.

Language: Английский

---

N-formylkynurenine but not kynurenine enters a nucleophile-scavenging branch of the immune-regulatory kynurenine pathway

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108219 - 108219

Published: Jan. 1, 2025

Language: Английский

---

Fueling Brain Inhibition: Integrating GABAergic Neurotransmission and Energy Metabolism

Neurochemical Research, Journal Year: 2025, Volume and Issue: 50(2)

Published: April 1, 2025

Language: Английский

---

Deficient brain GABA metabolism leads to widespread impairments of astrocyte and oligodendrocyte function

Glia, Journal Year: 2024, Volume and Issue: 72(10), P. 1821 - 1839

Published: June 20, 2024

Abstract The neurometabolic disorder succinic semialdehyde dehydrogenase (SSADH) deficiency leads to great neurochemical imbalances and severe neurological manifestations. cause of the disease is loss function enzyme SSADH, leading impaired metabolism principal inhibitory neurotransmitter GABA. Despite known identity enzymatic deficit, underlying pathology SSADH remains unclear. To uncover new mechanisms disease, we performed an untargeted integrative analysis cerebral protein expression, functional metabolism, lipid composition in a genetic mouse model (ALDH5A1 knockout mice). Our proteomic revealed clear regional vulnerability, as alterations primarily manifested hippocampus cortex ALDH5A1 mice. These regions displayed aberrant expression proteins linked amino acid homeostasis, mitochondria, glial function, myelination. Stable isotope tracing acutely isolated brain slices demonstrated overall maintained oxidative glucose, but selective decrease astrocyte metabolic activity In contrast, elevated capacity glutamine was observed brain, which may serve neuronal compensation provision. addition reduced critical oligodendrocyte proteins, depletion myelin‐enriched sphingolipids found brains mice, suggesting degeneration myelin. Altogether, our study highlights that intimately pathology, targeting cells hold therapeutic potential this disease.

Language: Английский

---

Metabolic preferences of astrocytes: Functional metabolic mapping reveals butyrate outcompetes acetate

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 28, 2024

Disruptions to the gut-brain-axis have been linked neurodegenerative disorders. Of these disruptions, reductions in levels of short-chain fatty acids (SCFAs), like butyrate, observed mouse models Alzheimer’s disease (AD). Butyrate supplementation mice has shown promise reducing neuroinflammation, amyloid-β accumulation, and enhancing memory. However, underlying mechanisms remain unclear. To address this, we investigated impact butyrate on energy metabolism brain slices, primary cultures astrocytes neurons in-vivo by dynamic isotope labelling with [U- 13 C]butyrate [1,2- C]acetate map via mass spectrometry. Metabolic competition assays cerebral cortical slices revealed no between ketone body, β-hydroxybutyrate, but acetate. Astrocytes favoured compared neurons, suggesting that astrocytic compartment is site metabolism. In-vivo 5xFAD mouse, an AD pathology model, showed difference C-labelling TCA cycle metabolites wild-type brains, remained elevated acetate both groups, indicating sustained uptake mice. Overall, findings highlight role potential use as alternative fuel source.

Language: Английский

---

Metabolic aspects of genetic ion channel epilepsies

Journal of Neurochemistry, Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 18, 2023

Abstract Nowadays, particularly in countries with high incomes, individual mutations people affected by genetic epilepsies are identified, and therapies being developed. In addition, drugs screened to directly target specific mutations, personalised medicine is possible. However, epilepsy do not yet benefit from these advances, many types of medication‐resistant, including Dravet syndrome. Thus, the meantime, alternative effective treatment options needed. There increasing evidence that metabolic deficits contribute epileptic seizures such impairments may be amenable treatment, like ketogenic diet employed some success. brain alterations occur ion channel well‐understood, nor how differ acquired unknown origins. Here, we provide an overview studies investigating caused SCN1A KCNA1 genes, which currently most studied animal models. The changes found models likely seizures. A basis supported human and/or show beneficial effects diet, mediated provision auxiliary fuel form ketone bodies. Other potentially more preferred dietary medium‐chain triglycerides triheptanoin have also been tested a limited number studies, but their efficacies remain clearly established. extent metabolism syndrome, thereof still requires clarification. This experiments yield functional insight into metabolism. image

Language: Английский

---

Stable isotope tracing reveals disturbed cellular energy and glutamate metabolism in hippocampal slices of aged male mice

Neurochemistry International, Journal Year: 2023, Volume and Issue: 171, P. 105626 - 105626

Published: Oct. 12, 2023

Neurons and astrocytes work in close metabolic collaboration, linking neurotransmission to brain energy neurotransmitter metabolism. Dysregulated metabolism is a hallmark of the aging may underlie progressive age-dependent cognitive decline. However, astrocyte remains understudied research. In particular, how affects glutamate, being primary excitatory neurotransmitter, still poorly understood. Here we investigated critical aspects cellular male mouse hippocampus using stable isotope tracing vitro. Metabolism [U-13C]glucose demonstrated an elevated glycolytic capacity aged hippocampal slices, whereas oxidative TCA cycle was significantly reduced with aging. addition, [1,2-13C]acetate, reflecting metabolism, likewise slices old mice. contrast, uptake subsequent [U-13C]glutamate elevated, suggesting increased for glutamate handling Finally, [15N]glutamate maintained demonstrating sustained nitrogen Collectively, this study reveals fundamental alterations brain, which contribute age-related deficits.

Language: Английский

---

Ex-Vivo ¹³C NMR Spectroscopy of Rodent Brain: TNF Restricts Neuronal Utilization of Astrocyte-Derived Metabolites

Journal of Proteome Research, Journal Year: 2024, Volume and Issue: 23(8), P. 3383 - 3392

Published: June 29, 2024

Tumor necrosis factor (TNF) has well-established roles in neuroinflammatory disorders, but the effect of TNF on biochemistry brain cells remains poorly understood. Here, we microinjected into to study its impact glial and neuronal metabolism (glycolysis, pentose phosphate pathway, citric acid cycle, pyruvate dehydrogenase, carboxylase pathways) using

Language: Английский

---

Misprogramming of glucose metabolism impairs recovery of hippocampal slices from neuronal GLT‐1 knockout mice and contributes to excitotoxic injury through mitochondrial superoxide production

Journal of Neurochemistry, Journal Year: 2024, Volume and Issue: 169(1)

Published: Aug. 28, 2024

We have previously reported a failure of recovery synaptic function in the CA1 region acute hippocampal slices from mice with conditional neuronal knockout (KO) GLT-1 (EAAT2, Slc1A2) driven by synapsin-Cre (synGLT-1 KO). The is due to excitotoxic injury. hypothesized that changes mitochondrial metabolism contribute heightened vulnerability excitotoxicity synGLT-1 KO mice. found impaired flux carbon

Language: Английский

---