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Homocysteine May Decrease Glucose Uptake and Alter the Akt/GSK3β/GLUT1 Signaling Pathway in Hippocampal Slices: Neuroprotective Effects of Rivastigmine and Ibuprofen.
- Source :
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Molecular neurobiology [Mol Neurobiol] 2023 Sep; Vol. 60 (9), pp. 5468-5481. Date of Electronic Publication: 2023 Jun 14. - Publication Year :
- 2023
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Abstract
- Homocysteine (Hcy) is a risk factor for neurodegenerative diseases, such as Alzheimer's Disease, and is related to cellular and tissue damage. In the present study, we verified the effect of Hcy on neurochemical parameters (redox homeostasis, neuronal excitability, glucose, and lactate levels) and the Serine/Threonine kinase B (Akt), Glucose synthase kinase-3β (GSK3β) and Glucose transporter 1 (GLUT1) signaling pathway in hippocampal slices, as well as the neuroprotective effects of ibuprofen and rivastigmine alone or in combination in such effects. Male Wistar rats (90 days old) were euthanized and the brains were dissected. The hippocampus slices were pre-treated for 30 min [saline medium or Hcy (30 µM)], then the other treatments were added to the medium for another 30 min [ibuprofen, rivastigmine, or ibuprofen + rivastigmine]. The dichlorofluorescein formed, nitrite and Na+, K+-ATPase activity was increased by Hcy at 30 µM. Ibuprofen reduced dichlorofluorescein formation and attenuated the effect of Hcy. The reduced glutathione content was reduced by Hcy. Treatments with ibuprofen and Hcy + ibuprofen increased reduced glutathione. Hcy at 30 µM caused a decrease in hippocampal glucose uptake and GLUT1 expression, and an increase in Glial Fibrillary Acidic Protein-protein expression. Phosphorylated GSK3β and Akt levels were reduced by Hcy (30 µM) and co-treatment with Hcy + rivastigmine + ibuprofen reversed these effects. Hcy toxicity on glucose metabolism can promote neurological damage. The combination of treatment with rivastigmine + ibuprofen attenuated such effects, probably by regulating the Akt/GSK3β/GLUT1 signaling pathway. Reversal of Hcy cellular damage by these compounds may be a potential neuroprotective strategy for brain damage.<br /> (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Subjects :
- Rats
Animals
Male
Proto-Oncogene Proteins c-akt metabolism
Rivastigmine pharmacology
Ibuprofen pharmacology
Glucose Transporter Type 1 metabolism
Rats, Wistar
Glycogen Synthase Kinase 3 beta metabolism
Signal Transduction
Hippocampus metabolism
Glutathione metabolism
Glucose metabolism
Homocysteine
Neuroprotective Agents pharmacology
Neuroprotective Agents metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1559-1182
- Volume :
- 60
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Molecular neurobiology
- Publication Type :
- Academic Journal
- Accession number :
- 37314655
- Full Text :
- https://doi.org/10.1007/s12035-023-03408-6