AI Article Synopsis
- Glutamate transporters, particularly EAAT3, are crucial for regulating glutamate levels and neurotransmission in the brain; dysfunction in EAAT3 can lead to seizures in rats.
- Research hypothesizes that the antiepileptic drug carbamazepine increases EAAT3 activity, and experiments show it enhances EAAT3 in oocytes and glioma cells at therapeutic concentrations.
- The enhancement of EAAT3 activity by carbamazepine occurs through a specific mechanism that decreases the enzyme's Km (affinity for glutamate) and is dependent on phosphatidylinositol 3-kinase (PI3K), suggesting EAAT3 could be a therapeutic target for managing seizures.
Article Abstract
Glutamate transporters (also called excitatory amino acid transporters, EAAT) participate in maintaining extracellular homeostasis of glutamate, a major excitatory neurotransmitter, and regulating glutamate neurotransmission. EAAT3, the major neuronal EAAT, may also regulate gamma-aminobutyric acid-mediated inhibitory neurotransmission. Dysfunction of EAAT3 has been shown to induce seizure in rats. We hypothesize that carbamazepine, a commonly used antiepileptic agent, enhances EAAT3 activity. We tested this hypothesis using oocytes artificially expressing EAAT3 and C6 rat glioma cells expressing endogenous EAAT3. In oocytes, carbamazepine dose-dependently enhanced EAAT3 activity. The EC50 of this carbamazepine effect was 12.2muM. The concentrations of carbamazepine to significantly enhance EAAT3 activity were within the therapeutic serum levels (17-51muM) of carbamazepine for the antiepileptic effect. Carbamazepine decreased the Km but did not change the maximal response of EAAT3 to glutamate. Carbamazepine-increased EAAT3 activity was inhibited by wortmannin or LY-294002, phosphatidylinositol 3-kinase (PI3K) inhibitors, but was not affected by staurosporine, chelerythrine or calphostin C, protein kinase C inhibitors. In C6 cells, carbamazepine also enhanced the endogenous EAAT3 activity. However, carbamazepine did not affect the activity of EAAT4 expressed in Cos7 cells. These results suggest that carbamazepine at clinically relevant concentrations specifically enhances the affinity of EAAT3 for glutamate to increase EAAT3 activity via a PI3K-dependent pathway. EAAT3 may be a therapeutic target for carbamazepine in the central nervous system.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.eplepsyres.2005.08.003 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Lactobacillus salivarius metabolite succinate enhances chicken intestinal stem cell activities via the SUCNR1-mitochondria axis.
Poult Sci
December 2024
MOA Key Laboratory of Animal Virology, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR China; Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR China. Electronic address:
Article Synopsis
- Intestinal stem cells (ISCs) in chickens can be influenced by Lactobacillus salivarius, enhancing nutrient transporters and supporting intestinal health.
- The study involved 189 chickens divided into 7 groups to assess the effects of Lactobacillus and succinate on mRNA levels related to amino acid transport and cell proliferation.
- Results showed that succinate from L. salivarius increases mRNA expression of key transporters and mitochondrial proteins, enhancing energy production in ISCs but can be inhibited by a receptor antagonist.
Increased forebrain EAAT3 expression confers resilience to chronic stress.
J Neurochem
January 2025
Centro Interdisciplinario de Neurociencia de Valparaíso (CINV), Universidad de Valparaíso, Valparaíso, Chile.
Article Synopsis
- Depression is a common mental illness linked to glutamate system dysfunction, with a specific focus on the neuronal glutamate transporter EAAT3 as a potential contributor to depressive-like behaviors.
- Research involving mice showed that those with increased EAAT3 expression in the forebrain were more resilient to developing depressive-like behaviors after undergoing chronic mild stress.
- Results indicated that EAAT3 overexpression not only protected these mice from depressive symptoms but also preserved their memory and normal synaptic activity, suggesting EAAT3's crucial role in mitigating the effects of chronic stress on mental health.
Dietary supplementation of microencapsulated botanicals and organic acids enhances the expression and function of intestine epithelial digestive enzymes and nutrient transporters in broiler chickens.
Poult Sci
November 2024
Department of Animal and Food Sciences, University of Delaware, 19716 Newark, DE, USA. Electronic address:
Article Synopsis
- The study investigated the effects of a microencapsulated blend of botanicals and organic acids on digestive enzymes and nutrient transporters in broilers, revealing beneficial impacts on gut health and growth performance.
- 288 birds were divided into a control group and a supplemented group, with significant improvements in feed efficiency and intestinal histology observed in the supplemented group after 21 days.
- Key findings included enhanced activities of enzymes like maltase and sucrase and increased expression of nutrient transporters, indicating that the blend positively influences nutrient absorption in the broilers.
Adolescent chemogenetic activation of dopaminergic neurons leads to reversible decreases in amphetamine-induced stereotypic behavior.
Mol Brain
June 2024
Department of Psychiatry, Columbia University Medical Center, New York, NY, 10032, USA.
Chronic perturbations of neuronal activity can evoke homeostatic and new setpoints for neurotransmission. Using chemogenetics to probe the relationship between neuronal cell types and behavior, we recently found reversible decreases in dopamine (DA) transmission, basal behavior, and amphetamine (AMPH) response following repeated stimulation of DA neurons in adult mice. It is unclear, however, whether altering DA neuronal activity via chemogenetics early in development leads to behavioral phenotypes that are reversible, as alterations of neuronal activity during developmentally sensitive periods might be expected to induce persistent effects on behavior.
View Article and Find Full Text PDFDietary apidaecin Api-PR19 addition enhances growth performance by regulating gut health and microbiota in broilers.
Anim Biosci
September 2024
College of Life Sciences, Northwest A&F University, Yangling, Shaanxi 712100, China.
Objective: This study investigated the effects of Apidaecin Api-PR19 as feed additive on growth performance, intestinal health, and small intestinal microbiota of broilers.
Methods: A total of 360 1-d-old Arbor Acres broilers were randomly assigned to 3 groups with 6 replicates including control group with basal diet (CON), antibiotic growth promotor group with basal plus 10 mg/kg colistin sulfate and 50 mg/kg roxarsone (AGP), and antibacterial peptide group with basal diet plus 330 mg/kg Apidaecin Api-PR19 (ABP). The trial lasted 35 d.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!