Astrocyte activation in the anterior cingulate cortex and altered glutamatergic gene expression during paclitaxel-induced neuropathic pain in mice
- Published
- Accepted
- Subject Areas
- Anesthesiology and Pain Management, Molecular Biology, Neuroscience, Pharmacology
- Keywords
- neuropathic pain, anterior cingulate cortex, astrocyte, paclitaxel, glutamate, glutamate receptors, glutamate transporters
- 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
- 2015. Astrocyte activation in the anterior cingulate cortex and altered glutamatergic gene expression during paclitaxel-induced neuropathic pain in mice. PeerJ PrePrints 3:e1246v2 https://doi.org/10.7287/peerj.preprints.1246v2
Abstract
Spinal astrocyte activation contributes to the pathogenesis of paclitaxel-induced neuropathic pain (PINP) in animal models. We examined glial fibrillary acidic protein (GFAP; an astrocyte marker) immunoreactivity and gene expression of GFAP, glutamate transporters and receptor subunits by real time PCR in the anterior cingulate cortex (ACC) at 7 days post first administration of paclitaxel, a time point when mice had developed thermal hyperalgesia. The ACC, an area in the brain involved in pain perception and modulation, was chosen because changes in this area might contribute to the pathophysiology of PINP. GFAP transcripts levels were elevated by more than fivefold and GFAP immunoreactivity increased 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 mGLuR8 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
The manuscript has been submitted to PeerJ for peer review. Astrocyte activation and changes in gene expression of the glutamatergic system in the anterior cingulate cortex area of the brain was studied in mice during paclitaxel-induced neuropathic pain. Paclitaxel is a used for treating cancer but produces neuropathic pain as one of its adverse effects.
