Effect of teriflunomide on cortex-basal ganglia-thalamus (CxBGTh) circuit glutamatergic dysregulation in the Theiler's Murine Encephalomyelitis Virus mouse model of multiple sclerosis.
Pathology of gray matter is associated with development of physical and cognitive disability in patients with multiple sclerosis. In particular, glutamatergic dysregulation in the cortex-basal ganglia-thalamus (CxBGTh) circuit could be associated with decline in these behaviors.To investigate the ef...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5552032?pdf=render |
| _version_ | 1818056900853366784 |
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| author | Claire M Modica Ferdinand Schweser Michelle L Sudyn Nicola Bertolino Marilena Preda Paul Polak Danielle M Siebert Jacqueline C Krawiecki Michele Sveinsson Jesper Hagemeier Michael G Dwyer Suyog Pol Robert Zivadinov |
| author_facet | Claire M Modica Ferdinand Schweser Michelle L Sudyn Nicola Bertolino Marilena Preda Paul Polak Danielle M Siebert Jacqueline C Krawiecki Michele Sveinsson Jesper Hagemeier Michael G Dwyer Suyog Pol Robert Zivadinov |
| author_sort | Claire M Modica |
| collection | DOAJ |
| description | Pathology of gray matter is associated with development of physical and cognitive disability in patients with multiple sclerosis. In particular, glutamatergic dysregulation in the cortex-basal ganglia-thalamus (CxBGTh) circuit could be associated with decline in these behaviors.To investigate the effect of an immunomodulatory therapy (teriflunomide, Aubagio®) on changes of the CxBGTh loop in the Theiler's Murine Encephalomyelitis Virus, (TMEV) mouse model of MS.Forty-eight (48) mice were infected with TMEV, treated with teriflunomide (24) or control vehicle (24) and followed for 39 weeks. Mice were examined with MRS and volumetric MRI scans (0, 8, 26, and 39 weeks) in the cortex, basal ganglia and thalamus, using a 9.4T scanner, and with behavioral tests (0, 4, 8, 12, 17, 26, and 39 weeks). Within conditions, MRI measures were compared between two time points by paired samples t-test and across multiple time points by repeated measures ANOVA (rmANOVA), and between conditions by independent samples t-test and rmANOVA, respectively. Data were considered as significant at the p<0.01 level and as a trend at p<0.05 level.In the thalamus, the teriflunomide arm exhibited trends toward decreased glutamate levels at 8 and 26 weeks compared to the control arm (p = 0.039 and p = 0.026), while the control arm exhibited a trend toward increased glutamate between 0 to 8 weeks (p = 0.045). In the basal ganglia, the teriflunomide arm exhibited a trend toward decreased glutamate earlier than the control arm, from 0 to 8 weeks (p = 0.011), resulting in decreased glutamate compared to the control arm at 8 weeks (p = 0.016).Teriflunomide may reduce possible excitotoxicity in the thalamus and basal ganglia by lowering glutamate levels. |
| first_indexed | 2024-12-10T12:36:12Z |
| format | Article |
| id | doaj.art-19a66a2f09514348bed115a0b088defc |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T12:36:12Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-19a66a2f09514348bed115a0b088defc2022-12-22T01:48:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01128e018272910.1371/journal.pone.0182729Effect of teriflunomide on cortex-basal ganglia-thalamus (CxBGTh) circuit glutamatergic dysregulation in the Theiler's Murine Encephalomyelitis Virus mouse model of multiple sclerosis.Claire M ModicaFerdinand SchweserMichelle L SudynNicola BertolinoMarilena PredaPaul PolakDanielle M SiebertJacqueline C KrawieckiMichele SveinssonJesper HagemeierMichael G DwyerSuyog PolRobert ZivadinovPathology of gray matter is associated with development of physical and cognitive disability in patients with multiple sclerosis. In particular, glutamatergic dysregulation in the cortex-basal ganglia-thalamus (CxBGTh) circuit could be associated with decline in these behaviors.To investigate the effect of an immunomodulatory therapy (teriflunomide, Aubagio®) on changes of the CxBGTh loop in the Theiler's Murine Encephalomyelitis Virus, (TMEV) mouse model of MS.Forty-eight (48) mice were infected with TMEV, treated with teriflunomide (24) or control vehicle (24) and followed for 39 weeks. Mice were examined with MRS and volumetric MRI scans (0, 8, 26, and 39 weeks) in the cortex, basal ganglia and thalamus, using a 9.4T scanner, and with behavioral tests (0, 4, 8, 12, 17, 26, and 39 weeks). Within conditions, MRI measures were compared between two time points by paired samples t-test and across multiple time points by repeated measures ANOVA (rmANOVA), and between conditions by independent samples t-test and rmANOVA, respectively. Data were considered as significant at the p<0.01 level and as a trend at p<0.05 level.In the thalamus, the teriflunomide arm exhibited trends toward decreased glutamate levels at 8 and 26 weeks compared to the control arm (p = 0.039 and p = 0.026), while the control arm exhibited a trend toward increased glutamate between 0 to 8 weeks (p = 0.045). In the basal ganglia, the teriflunomide arm exhibited a trend toward decreased glutamate earlier than the control arm, from 0 to 8 weeks (p = 0.011), resulting in decreased glutamate compared to the control arm at 8 weeks (p = 0.016).Teriflunomide may reduce possible excitotoxicity in the thalamus and basal ganglia by lowering glutamate levels.http://europepmc.org/articles/PMC5552032?pdf=render |
| spellingShingle | Claire M Modica Ferdinand Schweser Michelle L Sudyn Nicola Bertolino Marilena Preda Paul Polak Danielle M Siebert Jacqueline C Krawiecki Michele Sveinsson Jesper Hagemeier Michael G Dwyer Suyog Pol Robert Zivadinov Effect of teriflunomide on cortex-basal ganglia-thalamus (CxBGTh) circuit glutamatergic dysregulation in the Theiler's Murine Encephalomyelitis Virus mouse model of multiple sclerosis. PLoS ONE |
| title | Effect of teriflunomide on cortex-basal ganglia-thalamus (CxBGTh) circuit glutamatergic dysregulation in the Theiler's Murine Encephalomyelitis Virus mouse model of multiple sclerosis. |
| title_full | Effect of teriflunomide on cortex-basal ganglia-thalamus (CxBGTh) circuit glutamatergic dysregulation in the Theiler's Murine Encephalomyelitis Virus mouse model of multiple sclerosis. |
| title_fullStr | Effect of teriflunomide on cortex-basal ganglia-thalamus (CxBGTh) circuit glutamatergic dysregulation in the Theiler's Murine Encephalomyelitis Virus mouse model of multiple sclerosis. |
| title_full_unstemmed | Effect of teriflunomide on cortex-basal ganglia-thalamus (CxBGTh) circuit glutamatergic dysregulation in the Theiler's Murine Encephalomyelitis Virus mouse model of multiple sclerosis. |
| title_short | Effect of teriflunomide on cortex-basal ganglia-thalamus (CxBGTh) circuit glutamatergic dysregulation in the Theiler's Murine Encephalomyelitis Virus mouse model of multiple sclerosis. |
| title_sort | effect of teriflunomide on cortex basal ganglia thalamus cxbgth circuit glutamatergic dysregulation in the theiler s murine encephalomyelitis virus mouse model of multiple sclerosis |
| url | http://europepmc.org/articles/PMC5552032?pdf=render |
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