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Permanent link (DOI): https://doi.org/10.7939/R3TQ42

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Effects of long-term inhibition of EAAT2 on the excitability of spinal dorsal horn neurons Open Access

Descriptions

Other title
Subject/Keyword
Neuropathic pain
EAAT2
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Kim, Helena J
Supervisor and department
Smith, Peter A (Pharmacology)
Examining committee member and department
Ballanyi, Klaus (Physiology)
Kerr, Bradley J (Anesthesiology and Pain Medicine)
Department
Centre for Neuroscience
Specialization

Date accepted
2010-11-09T19:13:12Z
Graduation date
2011-06
Degree
Master of Science
Degree level
Master's
Abstract
This thesis examined the effects of long-term inhibition of excitatory amino acid transporter 2 (EAAT2) on the excitability of dorsal horn neurons in defined-medium organotypic slice cultures (DMOTCs). Previous reports suggest that inhibition of EAAT2 may be involved in development of neuropathic pain induced by brain-derived neurotrophic factor (BDNF). Experiments were carried out using confocal Ca2+ imaging to assess the excitability of dorsal horn neurons. Long-term treatment with EAAT2 blocker, dihydrokainate (DHK), prominently increased the neuronal excitability. Long-term exposure to DHK had a significant effect on NMDA, AMPA and metabotropic glutamate subtype 1 (mGluR1) receptors. Lastly, long-term treatment with BDNF and DHK increased activity of AMPA receptors but only DHK significantly increased activity of NMDA receptors. These findings suggest inhibition of EAAT2 and BDNF may have different pathways to promote neuropathic pain and modulating the activity of EAAT2 may be a novel therapeutic approach for neuropathic pain.
Language
English
DOI
doi:10.7939/R3TQ42
Rights
License granted by Helena Kim (helena3@ualberta.ca) on 2010-11-05T06:04:57Z (GMT): Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of the above terms. The author reserves all other publication and other rights in association with the copyright in the thesis, and except as herein provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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