Objective: Glutamate transporter-1 (GLT-1) and system x mediate glutamate uptake and release, respectively. Ceftriaxone has been reported to upregulate GLT-1 expression and improve cognitive decline in APP/PS1 mice. The aim of the present study was to elucidate the role of GLT-1 in ceftriaxone-mediated improvement on cognitive deficits and associated changes in xCT (catalytic subunit of system x ) expression and activity using GLT-1 knockdown APP/PS1 mice.
Methods: GLT-1 knockdown (GLT-1) mice were generated in C57BL/6J mice using the CRISPR/Cas9 technique and crossed to APP/PS1 mice to generate GLT-1APP/PS1 mice. The cognition was evaluated by novel object recognition and Morris water maze tests. GLT-1 and xCT expression, GLT-1 uptake for glutamate, and glutathione levels of hippocampus were assayed using Western blot and immunohistochemistry, H-glutamate, and glutathione assay kit, respectively.
Results: In comparison with wild-type mice, APP/PS1 mice exhibited significant cognitive deficits, represented with poor performance in novel object recognition and Morris water maze tests, downregulated GLT-1 expression and glutamate uptake. Ceftriaxone treatment significantly improved the above impairments in APP/PS1 mice, but had negligible impact in GLT-1APP/PS1 mice. The xCT expression increased in APP/PS1 and GLT-1APP/PS1 mice. This upregulation might be a compensatory change against the accumulated glutamate resulting from GLT-1 impairment. Ceftriaxone treatment restored xCT expression in APP/PS1 mice, but not in GLT-1APP/PS1 mice. Glutathione levels decreased in APP/PS1 mice in comparison to the wild-type group. After ceftriaxone administration, the decline in glutathione level was restored in APP/PS1 mice, but not in GLT-1APP/PS1 mice.
Conclusion: Ceftriaxone improves cognitive impairment of APP/PS1 mice by upregulating GLT-1-mediated uptake of glutamate and co-regulation of GLT-1 and xCT in APP/PS1 mice.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574737 | PMC |
| http://dx.doi.org/10.3389/fnagi.2020.580772 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Fecal Microbiota Transplantation from Methionine-Restricted Diet Mouse Donors Improves Alzheimer's Learning and Memory Abilities Through Short-Chain Fatty Acids.
Foods
January 2025
School of Public Health, Health Science Center, Ningbo University, Ningbo 315211, China.
Alzheimer's disease (AD) is marked by impaired cognitive functions, particularly in learning and memory, owing to complex and diverse mechanisms. Methionine restriction (MR) has been found to exert a mitigating effect on brain oxidative stress to improve AD. However, the bidirectional crosstalk between the gut and brain through which MR enhances learning and memory in AD, as well as the effects of fecal microbiota transplantation (FMT) from MR mice on AD mice, remains underexplored.
View Article and Find Full Text PDFSENP1 inhibits aerobic glycolysis in Aβ-incubated astrocytes by promoting PUM2 deSUMOylation.
Cell Biol Toxicol
January 2025
Department of Neurology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
Alzheimer's disease (AD), the most prevalent form of dementia in the elderly, involves critical changes such as reduced aerobic glycolysis in astrocytes and increased neuronal apoptosis, both of which are significant in the disease's pathology. In our study, astrocytes treated with amyloid β1-42 (Aβ) to simulate AD conditions exhibited upregulated expressions of small ubiquitin-like modifier (SUMO)-specific protease 1 (SENP1) and Pumilio RNA Binding Family Member 2 (PUM2), alongside decreased levels of Nuclear factor erythroid 2-related factor 2 (NRF2). SENP1 is notably the most upregulated SUMOylation enzyme in Aβ-exposed astrocytes.
View Article and Find Full Text PDFProtection of Alzheimer's disease progression by a human-origin probiotics cocktail.
Sci Rep
January 2025
USF Center for Microbiome Research, Microbiomes Institute, University of South Florida Morsani College of Medicine, Tampa, FL, 33612, USA.
Microbiome abnormalities (dysbiosis) significantly contribute to the progression of Alzheimer's disease (AD). However, the therapeutic efficacy of microbiome modulators in protecting against these ailments remains poorly studied. Herein, we tested a cocktail of unique probiotics, including 5 Lactobacillus and 5 Enterococcus strains isolated from infant gut with proven microbiome modulating capabilities.
View Article and Find Full Text PDFOAB-14 alleviates mitochondrial impairment through the SIRT3-dependent mechanism in APP/PS1 transgenic mice and N2a/APP cells.
Free Radic Biol Med
January 2025
Department of Pharmacology, Shenyang Pharmaceutical University103 Wenhua Road, Shenhe District, Shenyang Liaoning, 110016, P.R. China. Electronic address:
Alzheimer's disease (AD) is a progressive degenerative disease that affects a growing number of elderly individuals worldwide. OAB-14, a novel chemical compound developed by our research group, has been approved by the China Food and Drug Administration (FDA) for clinical trials in patients with AD (approval no. YD-OAB-220210).
View Article and Find Full Text PDFElevation of ganglioside degradation pathway drives GM2 and GM3 within amyloid plaques in a transgenic mouse model of Alzheimer's disease.
Neurobiol Dis
January 2025
Vulnerable Brain Lab, Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, Ontario N6A 5C1, Canada. Electronic address:
Alzheimer's disease (AD) is a progressive neurodegenerative disease that accounts for two-thirds of all dementia cases, and age is the strongest risk factor. In addition to the amyloid hypothesis, lipid dysregulation is now recognized as a core component of AD pathology. Gangliosides are a class of membrane lipids of the glycosphingolipid family and are enriched in the central nervous system (CNS).
View Article and Find Full Text PDFWant 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!