Astrocyte activation in the anterior cingulate cortex and altered glutamatergic gene expression during paclitaxel-induced neuropathic pain in mice

Department Pharmacology and Therapeutics, Faculty of Pharmacy, Kuwait University, Safat, Kuwait
DOI
10.7287/peerj.preprints.1246v1
Subject Areas
Anesthesiology and Pain Management, Molecular Biology, Neuroscience, Pharmacology
Keywords
Paclitaxel, anterior cingulate cortex, neuropathic-pain, glutamate transporters, glutamate receptors, astrocytes
Copyright
© 2015 Masocha
Licence
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ PrePrints) and either DOI or URL of the article must be cited.
Cite this article
Masocha W. 2015. Astrocyte activation in the anterior cingulate cortex and altered glutamatergic gene expression during paclitaxel-induced neuropathic pain in mice. PeerJ PrePrints 3:e1246v1

Abstract

Spinal astrocyte activation contributes to the pathogenesis of paclitaxel-induced neuropathic pain (PINP) in animal models. We examined gene expression of glial fibrillary acidic protein (GFAP; an astrocyte marker), glutamate transporters and receptor subunits in the anterior cingulate cortex (ACC) by real time PCR at 7 days post first administration of paclitaxel, a time point when mice had developed thermal hyperalgesia. Changes in the ACC, an area in the brain involved in pain perception and modulation, might contribute to the pathophysiology of PINP. GFAP transcripts levels were elevated by more than fivefold in the ACC of paclitaxel-treated mice. The 6 glutamate transporters (GLAST, GLT-1 EAAC1, EAAT4, VGLUT-1 and VGLUT-2) quantified were not significantly altered by paclitaxel treatment. Of the 12 ionotropic glutamate receptor subunits transcripts analysed 6 (GLuA1, GLuA3, GLuK2, GLuK3, GLuK5 and GLuN1) were significantly up-regulated, whereas GLuA2, GLuK1, GLuK4, GLuN2A and GLuN2B were not significantly altered and GLuA4 was lowly expressed. Amongst the 8 metabotropic receptor subunits analysed only mGLuR 8 was significantly elevated. In conclusion, during PINP there is astrocyte activation, no change in glutamate transporter expression and differential up-regulation of glutamate receptor subunits in the ACC. Thus, targeting astrocyte activation and the glutamatergic system might be another therapeutic avenue for management of PINP.

Author Comment

This is a submission to PeerJ for review.

Supplemental Information

Raw data - Relative expression of mRNA for GFAP

DOI: 10.7287/peerj.preprints.1246v1/supp-1

Raw data - Relative expression of mRNA for glutamate transporters

DOI: 10.7287/peerj.preprints.1246v1/supp-2

Raw data - Relative expression of mRNA for kainate glutamate receptor subunits

DOI: 10.7287/peerj.preprints.1246v1/supp-3

Raw data - Relative expression of mRNA for kainate glutamate receptor subunits

DOI: 10.7287/peerj.preprints.1246v1/supp-4

Raw data - Relative expression of mRNA for NMDA glutamate receptor subunits

DOI: 10.7287/peerj.preprints.1246v1/supp-5

Raw data - Relative expression of mRNA for metabotropic glutamate receptor

DOI: 10.7287/peerj.preprints.1246v1/supp-6