Glutamatergic Alterations in STZ-Induced Diabetic Rats Are Reversed by Exendin-4

Molecular Neurobiology
Caroline ZanottoCarlos-Alberto Gonçalves

Abstract

Diabetes mellitus is a metabolic disorder that results in glucotoxicity and the formation of advanced glycated end products (AGEs), which mediate several systemic adverse effects, particularly in the brain tissue. Alterations in glutamatergic neurotransmission and cognitive impairment have been reported in DM. Exendin-4 (EX-4), an analogue of glucagon-like peptide-1 (GLP-1), appears to have beneficial effects on cognition in rats with chronic hyperglycemia. Herein, we investigated the ability of EX-4 to reverse changes in AGE content and glutamatergic transmission in an animal model of DM looking principally at glutamate uptake and GluN1 subunit content of the N-methyl-D-aspartate (NMDA) receptor. Additionally, we evaluated the effects of EX-4 on in vitro models and the signaling pathway involved in these effects. We found a decrease in glutamate uptake and GluN1 content in the hippocampus of diabetic rats; EX-4 was able to revert these parameters, but had no effect on the other parameters evaluated (glycemia, C-peptide, AGE levels, RAGE, and glyoxalase 1). EX-4 abrogated the decrease in glutamate uptake and GluN1 content caused by methylglyoxal (MG) in hippocampal slices, in addition to leading to an increase in glutamate upta...Continue Reading

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Citations

May 5, 2021·The International Journal of Neuroscience·LongQing ZhangXueBi Tian
Jul 15, 2021·Neurotoxicity Research·Vanessa SovraniAndré Quincozes-Santos
Jul 3, 2021·Expert Opinion on Investigational Drugs·Jonathan FlintoffThomas Hj Burne

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay

Software Mentioned

GraphPad
PRISM

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