Steroid protection in the experimental autoimmune encephalomyelitis model of multiple sclerosis
Objectives: Based on evidence that pregnant women with multiple sclerosis (MS) show a decline in the relapse rate during the third trimester and an increase during the first 3 months postpartum, the suggestion was made that high levels of circulating sex steroids are responsible for pregnancy-mediat...
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2008
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10217401_v15_n1_p76_Garay http://hdl.handle.net/20.500.12110/paper_10217401_v15_n1_p76_Garay |
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paper:paper_10217401_v15_n1_p76_Garay2023-06-08T16:00:00Z Steroid protection in the experimental autoimmune encephalomyelitis model of multiple sclerosis Estradiol Experimental autoimmune encephalomyelitis Multiple sclerosis Myelination Neuroprotection Progesterone 1,3,5 tris(4 hydroxyphenyl) 4 propylpyrazole adenosine triphosphatase (potassium sodium) brain derived neurotrophic factor estradiol estriol ethinylestradiol fluasterone glucocorticoid medroxyprogesterone myelin basic protein myelin oligodendrocyte glycoprotein prasterone progesterone proteolipid protein tetrahydroprogesterone allergic encephalomyelitis brain function cell infiltration cell proliferation cellular immunity demyelination disease course drug activity drug effect drug megadose estrogen activity hormonal regulation hormone action human low drug dose multiple sclerosis myelin sheath myelination neuroprotection nonhuman pathogenesis priority journal protein expression quantitative analysis review theoretical model third trimester pregnancy Animals Brain-Derived Neurotrophic Factor Central Nervous System Disease Models, Animal Drug Synergism Drug Therapy, Combination Encephalomyelitis, Autoimmune, Experimental Estradiol Female Humans Mice Mice, Inbred C57BL Multiple Sclerosis Myelin Basic Proteins Myelin Proteolipid Protein Nerve Fibers, Myelinated Neurosecretory Systems Progesterone RNA, Messenger Sodium-Potassium-Exchanging ATPase Treatment Outcome Up-Regulation Objectives: Based on evidence that pregnant women with multiple sclerosis (MS) show a decline in the relapse rate during the third trimester and an increase during the first 3 months postpartum, the suggestion was made that high levels of circulating sex steroids are responsible for pregnancy-mediated neuroprotection. As both estradiol (E2) and progesterone exert neuroprotective and myelinating effects on the nervous system, the effects of sex steroids were studied in the experimental autoimmune encephalomyelitis (EAE) model of MS. Methods: EAE was induced in female C57BL/6 mice by administration of a myelin oligodendrocyte protein (MOG40-45) peptide. Clinical signs of EAE, myelin protein expression and neuronal parameters were determined in mice with or without hormonal treatment. Results: Progesterone given prior to EAE induction attenuated the clinical scores of the disease, slightly delayed disease onset and decreased demyelination foci, according to luxol fast blue staining (LFB), myelin basic protein (MBP) and proteolipid protein (PLP) and mRNA expression. Motoneuron expression of Na,K-ATPase mRNA was also enhanced by progesterone. In turn, combined E2 plus progesterone therapy more effectively prevented neurological deficits, fully restored LFB staining, MBP and PLP immunoreactivity and avoided inflammatory cell infiltration. On the neuronal side, steroid biotherapy increased brain-derived neurotrophic factor (BDNF) mRNA. Conclusion: Early treatment with progesterone alone or more evidently in combination with E2 showed a clinical benefit and produced myelinating and neuroprotective effects in mice with MOG 40-45-induced EAE. Therefore, sex steroids should be considered as potential novel therapeutic strategies for MS. Copyright © 2008 S. Karger AG. 2008 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10217401_v15_n1_p76_Garay http://hdl.handle.net/20.500.12110/paper_10217401_v15_n1_p76_Garay |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Estradiol Experimental autoimmune encephalomyelitis Multiple sclerosis Myelination Neuroprotection Progesterone 1,3,5 tris(4 hydroxyphenyl) 4 propylpyrazole adenosine triphosphatase (potassium sodium) brain derived neurotrophic factor estradiol estriol ethinylestradiol fluasterone glucocorticoid medroxyprogesterone myelin basic protein myelin oligodendrocyte glycoprotein prasterone progesterone proteolipid protein tetrahydroprogesterone allergic encephalomyelitis brain function cell infiltration cell proliferation cellular immunity demyelination disease course drug activity drug effect drug megadose estrogen activity hormonal regulation hormone action human low drug dose multiple sclerosis myelin sheath myelination neuroprotection nonhuman pathogenesis priority journal protein expression quantitative analysis review theoretical model third trimester pregnancy Animals Brain-Derived Neurotrophic Factor Central Nervous System Disease Models, Animal Drug Synergism Drug Therapy, Combination Encephalomyelitis, Autoimmune, Experimental Estradiol Female Humans Mice Mice, Inbred C57BL Multiple Sclerosis Myelin Basic Proteins Myelin Proteolipid Protein Nerve Fibers, Myelinated Neurosecretory Systems Progesterone RNA, Messenger Sodium-Potassium-Exchanging ATPase Treatment Outcome Up-Regulation |
| spellingShingle |
Estradiol Experimental autoimmune encephalomyelitis Multiple sclerosis Myelination Neuroprotection Progesterone 1,3,5 tris(4 hydroxyphenyl) 4 propylpyrazole adenosine triphosphatase (potassium sodium) brain derived neurotrophic factor estradiol estriol ethinylestradiol fluasterone glucocorticoid medroxyprogesterone myelin basic protein myelin oligodendrocyte glycoprotein prasterone progesterone proteolipid protein tetrahydroprogesterone allergic encephalomyelitis brain function cell infiltration cell proliferation cellular immunity demyelination disease course drug activity drug effect drug megadose estrogen activity hormonal regulation hormone action human low drug dose multiple sclerosis myelin sheath myelination neuroprotection nonhuman pathogenesis priority journal protein expression quantitative analysis review theoretical model third trimester pregnancy Animals Brain-Derived Neurotrophic Factor Central Nervous System Disease Models, Animal Drug Synergism Drug Therapy, Combination Encephalomyelitis, Autoimmune, Experimental Estradiol Female Humans Mice Mice, Inbred C57BL Multiple Sclerosis Myelin Basic Proteins Myelin Proteolipid Protein Nerve Fibers, Myelinated Neurosecretory Systems Progesterone RNA, Messenger Sodium-Potassium-Exchanging ATPase Treatment Outcome Up-Regulation Steroid protection in the experimental autoimmune encephalomyelitis model of multiple sclerosis |
| topic_facet |
Estradiol Experimental autoimmune encephalomyelitis Multiple sclerosis Myelination Neuroprotection Progesterone 1,3,5 tris(4 hydroxyphenyl) 4 propylpyrazole adenosine triphosphatase (potassium sodium) brain derived neurotrophic factor estradiol estriol ethinylestradiol fluasterone glucocorticoid medroxyprogesterone myelin basic protein myelin oligodendrocyte glycoprotein prasterone progesterone proteolipid protein tetrahydroprogesterone allergic encephalomyelitis brain function cell infiltration cell proliferation cellular immunity demyelination disease course drug activity drug effect drug megadose estrogen activity hormonal regulation hormone action human low drug dose multiple sclerosis myelin sheath myelination neuroprotection nonhuman pathogenesis priority journal protein expression quantitative analysis review theoretical model third trimester pregnancy Animals Brain-Derived Neurotrophic Factor Central Nervous System Disease Models, Animal Drug Synergism Drug Therapy, Combination Encephalomyelitis, Autoimmune, Experimental Estradiol Female Humans Mice Mice, Inbred C57BL Multiple Sclerosis Myelin Basic Proteins Myelin Proteolipid Protein Nerve Fibers, Myelinated Neurosecretory Systems Progesterone RNA, Messenger Sodium-Potassium-Exchanging ATPase Treatment Outcome Up-Regulation |
| description |
Objectives: Based on evidence that pregnant women with multiple sclerosis (MS) show a decline in the relapse rate during the third trimester and an increase during the first 3 months postpartum, the suggestion was made that high levels of circulating sex steroids are responsible for pregnancy-mediated neuroprotection. As both estradiol (E2) and progesterone exert neuroprotective and myelinating effects on the nervous system, the effects of sex steroids were studied in the experimental autoimmune encephalomyelitis (EAE) model of MS. Methods: EAE was induced in female C57BL/6 mice by administration of a myelin oligodendrocyte protein (MOG40-45) peptide. Clinical signs of EAE, myelin protein expression and neuronal parameters were determined in mice with or without hormonal treatment. Results: Progesterone given prior to EAE induction attenuated the clinical scores of the disease, slightly delayed disease onset and decreased demyelination foci, according to luxol fast blue staining (LFB), myelin basic protein (MBP) and proteolipid protein (PLP) and mRNA expression. Motoneuron expression of Na,K-ATPase mRNA was also enhanced by progesterone. In turn, combined E2 plus progesterone therapy more effectively prevented neurological deficits, fully restored LFB staining, MBP and PLP immunoreactivity and avoided inflammatory cell infiltration. On the neuronal side, steroid biotherapy increased brain-derived neurotrophic factor (BDNF) mRNA. Conclusion: Early treatment with progesterone alone or more evidently in combination with E2 showed a clinical benefit and produced myelinating and neuroprotective effects in mice with MOG 40-45-induced EAE. Therefore, sex steroids should be considered as potential novel therapeutic strategies for MS. Copyright © 2008 S. Karger AG. |
| title |
Steroid protection in the experimental autoimmune encephalomyelitis model of multiple sclerosis |
| title_short |
Steroid protection in the experimental autoimmune encephalomyelitis model of multiple sclerosis |
| title_full |
Steroid protection in the experimental autoimmune encephalomyelitis model of multiple sclerosis |
| title_fullStr |
Steroid protection in the experimental autoimmune encephalomyelitis model of multiple sclerosis |
| title_full_unstemmed |
Steroid protection in the experimental autoimmune encephalomyelitis model of multiple sclerosis |
| title_sort |
steroid protection in the experimental autoimmune encephalomyelitis model of multiple sclerosis |
| publishDate |
2008 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10217401_v15_n1_p76_Garay http://hdl.handle.net/20.500.12110/paper_10217401_v15_n1_p76_Garay |
| _version_ |
1768542899009486848 |