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Aβ 1-42 Oligomers Induced a Short-Term Increase of Glutamate Release Prior to Its Depletion As Measured by Amperometry on Single Varicosities.
- Source :
-
Analytical chemistry [Anal Chem] 2019 Dec 03; Vol. 91 (23), pp. 15123-15129. Date of Electronic Publication: 2019 Nov 20. - Publication Year :
- 2019
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Abstract
- Glutamate (Glu) is a critical neurotransmitter for neuronal communication in the nervous system. In vivo studies have shown that the concentration of Glu is reduced within the brains of those afflicted with Alzheimer's disease (AD), which is also associated with the accumulation of pathogenic amyloid-beta (Aβ). However, the effects of Aβ peptides on the level of Glu release, as well as how Aβ-mediated Glu fluctuation is initiated, remain largely unknown. Here, we fabricated a Glu electrochemical biosensor and in situ quantitatively monitored the release of Glu from a single varicosity of Aβ <subscript>1-42</subscript> -insulted hippocampal neurons. We found that before the depletion of Glu after 300 min of treatment with Aβ <subscript>1-42</subscript> , a short-duration (30 min) incubation with Aβ <subscript>1-42</subscript> caused a dramatic increase in vesicular Glu release compared to that of a control. Further investigation demonstrated that the density of vesicular glutamate transporter 1 (VGLUT1), which is responsible for transport of Glu into synaptic vesicles, also displayed a significant elevation and then dramatic depletion with the extension of the time of treatment with Aβ <subscript>1-42</subscript> . These results indicate that at the early stage of AD, Aβ <subscript>1-42</subscript> induces excessive Glu release, which may overstimulate the N -methyl-d-aspartic acid (NMDA) receptor, resulting in excitotoxicity and damage to neurons. In this work, the amount of Glu released together with its fluctuations under Aβ <subscript>1-42</subscript> oligomers toxicity conditions was monitored for the first time, and such monitoring could provide direct and new insights for current research on Aβ <subscript>1-42</subscript> -induced abnormalities in neurotransmitter release and neuron functions.
- Subjects :
- Animals
Electrochemistry methods
Glutamic Acid deficiency
Glutamic Acid drug effects
Hippocampus metabolism
Humans
Neurons physiology
Time Factors
Vesicular Glutamate Transport Protein 1 metabolism
Alzheimer Disease metabolism
Amyloid beta-Peptides pharmacology
Biosensing Techniques methods
Glutamic Acid metabolism
Peptide Fragments pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1520-6882
- Volume :
- 91
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- Analytical chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 31697073
- Full Text :
- https://doi.org/10.1021/acs.analchem.9b03826