Chronic immobilisation stress ameliorates clinical score and neuroinflammation in a MOG-induced EAE in Dark Agouti rats: mechanisms implicated
<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis (MS) is the endpoint of a complex and still poorly understood process which results in inflammation, demyelination and axonal and neuronal degeneration. Since the first description of MS, psychological stress has b...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2010-10-01
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| Series: | Journal of Neuroinflammation |
| Online Access: | http://www.jneuroinflammation.com/content/7/1/60 |
| _version_ | 1818229277251862528 |
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| author | Madrigal José LM García-Bueno Borja Pérez-Nievas Beatriz G Leza Juan C |
| author_facet | Madrigal José LM García-Bueno Borja Pérez-Nievas Beatriz G Leza Juan C |
| author_sort | Madrigal José LM |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Multiple sclerosis (MS) is the endpoint of a complex and still poorly understood process which results in inflammation, demyelination and axonal and neuronal degeneration. Since the first description of MS, psychological stress has been suggested to be one of the trigger factors in the onset and/or relapse of symptoms. However, data from animal models of MS, such as experimental autoimmune encephalomyelitis (EAE) are inconsistent and the effect of stress on EAE onset and severity depends on duration and time of application of the stress protocol and the underlying mechanisms.</p> <p>Methods</p> <p>Dark Agouti rats were inoculated with MOG/CFA to induce EAE, and an immobilisation stress protocol with two different durations (12 and 21 days, starting at the moment of MOG-inoculation) was applied in order to analyse the effect of stress on disease onset and neuroinflammation.</p> <p>Results</p> <p>Twelve days of stress exposure increased EAE clinical score in Dark Agouti rats. In addition, these animals presented higher levels of MMP-9 and proinflammatory PGE<sub>2 </sub>in spinal cord. In contrast, animals chronically exposed to stress (21 days) showed a significantly lower incidence of EAE clinical signs and reduced myelin loss, leukocyte infiltration and accumulation of inflammatory/oxidative mediators in spinal cord. Interestingly, chronically stressed animals showed a parallel increase in levels of the anti-inflammatory prostaglandin 15d-PGJ<sub>2</sub>, the main endogenous agonist of PPARγ.</p> <p>Conclusions</p> <p>Our results demonstrate that, depending on duration, stress exposure elicits opposite effects on PGE<sub>2</sub>/15d-PGJ<sub>2 </sub>ratios in spinal cord of EAE-induced Dark Agouti rats. Further studies are needed to elucidate if these changes in prostaglandin balance are sufficient to mediate the differences in clinical score and inflammation here reported, and to establish the potential utility of pharmacological intervention in MS directed toward anti-inflammatory pathways.</p> |
| first_indexed | 2024-12-12T10:16:03Z |
| format | Article |
| id | doaj.art-ac3ca59ba64441c798bedabf89651c60 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-12T10:16:03Z |
| publishDate | 2010-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-ac3ca59ba64441c798bedabf89651c602022-12-22T00:27:40ZengBMCJournal of Neuroinflammation1742-20942010-10-01716010.1186/1742-2094-7-60Chronic immobilisation stress ameliorates clinical score and neuroinflammation in a MOG-induced EAE in Dark Agouti rats: mechanisms implicatedMadrigal José LMGarcía-Bueno BorjaPérez-Nievas Beatriz GLeza Juan C<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis (MS) is the endpoint of a complex and still poorly understood process which results in inflammation, demyelination and axonal and neuronal degeneration. Since the first description of MS, psychological stress has been suggested to be one of the trigger factors in the onset and/or relapse of symptoms. However, data from animal models of MS, such as experimental autoimmune encephalomyelitis (EAE) are inconsistent and the effect of stress on EAE onset and severity depends on duration and time of application of the stress protocol and the underlying mechanisms.</p> <p>Methods</p> <p>Dark Agouti rats were inoculated with MOG/CFA to induce EAE, and an immobilisation stress protocol with two different durations (12 and 21 days, starting at the moment of MOG-inoculation) was applied in order to analyse the effect of stress on disease onset and neuroinflammation.</p> <p>Results</p> <p>Twelve days of stress exposure increased EAE clinical score in Dark Agouti rats. In addition, these animals presented higher levels of MMP-9 and proinflammatory PGE<sub>2 </sub>in spinal cord. In contrast, animals chronically exposed to stress (21 days) showed a significantly lower incidence of EAE clinical signs and reduced myelin loss, leukocyte infiltration and accumulation of inflammatory/oxidative mediators in spinal cord. Interestingly, chronically stressed animals showed a parallel increase in levels of the anti-inflammatory prostaglandin 15d-PGJ<sub>2</sub>, the main endogenous agonist of PPARγ.</p> <p>Conclusions</p> <p>Our results demonstrate that, depending on duration, stress exposure elicits opposite effects on PGE<sub>2</sub>/15d-PGJ<sub>2 </sub>ratios in spinal cord of EAE-induced Dark Agouti rats. Further studies are needed to elucidate if these changes in prostaglandin balance are sufficient to mediate the differences in clinical score and inflammation here reported, and to establish the potential utility of pharmacological intervention in MS directed toward anti-inflammatory pathways.</p>http://www.jneuroinflammation.com/content/7/1/60 |
| spellingShingle | Madrigal José LM García-Bueno Borja Pérez-Nievas Beatriz G Leza Juan C Chronic immobilisation stress ameliorates clinical score and neuroinflammation in a MOG-induced EAE in Dark Agouti rats: mechanisms implicated Journal of Neuroinflammation |
| title | Chronic immobilisation stress ameliorates clinical score and neuroinflammation in a MOG-induced EAE in Dark Agouti rats: mechanisms implicated |
| title_full | Chronic immobilisation stress ameliorates clinical score and neuroinflammation in a MOG-induced EAE in Dark Agouti rats: mechanisms implicated |
| title_fullStr | Chronic immobilisation stress ameliorates clinical score and neuroinflammation in a MOG-induced EAE in Dark Agouti rats: mechanisms implicated |
| title_full_unstemmed | Chronic immobilisation stress ameliorates clinical score and neuroinflammation in a MOG-induced EAE in Dark Agouti rats: mechanisms implicated |
| title_short | Chronic immobilisation stress ameliorates clinical score and neuroinflammation in a MOG-induced EAE in Dark Agouti rats: mechanisms implicated |
| title_sort | chronic immobilisation stress ameliorates clinical score and neuroinflammation in a mog induced eae in dark agouti rats mechanisms implicated |
| url | http://www.jneuroinflammation.com/content/7/1/60 |
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