PMID- 18667803
OWN - NLM
STAT- MEDLINE
DCOM- 20081029
LR  - 20191210
IS  - 1423-0216 (Electronic)
IS  - 1021-7401 (Linking)
VI  - 15
IP  - 1
DP  - 2008
TI  - Steroid protection in the experimental autoimmune encephalomyelitis model of 
      multiple sclerosis.
PG  - 76-83
LID - 10.1159/000135627 [doi]
AB  - 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 (E(2)) 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 (MOG(40-45)) 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 E(2) 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 E(2) 
      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.
CI  - Copyright 2008 S. Karger AG, Basel.
FAU - Garay, Laura
AU  - Garay L
AD  - Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina 
      Experimental-CONICET, Buenos Aires, Argentina.
FAU - Gonzalez Deniselle, Maria Claudia
AU  - Gonzalez Deniselle MC
FAU - Gierman, Lobke
AU  - Gierman L
FAU - Meyer, Maria
AU  - Meyer M
FAU - Lima, Analia
AU  - Lima A
FAU - Roig, Paulina
AU  - Roig P
FAU - De Nicola, Alejandro F
AU  - De Nicola AF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080729
PL  - Switzerland
TA  - Neuroimmunomodulation
JT  - Neuroimmunomodulation
JID - 9422763
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Myelin Basic Protein)
RN  - 0 (Myelin Proteolipid Protein)
RN  - 0 (RNA, Messenger)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 7.2.2.13 (Sodium-Potassium-Exchanging ATPase)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics
MH  - Central Nervous System/drug effects/pathology/physiopathology
MH  - Disease Models, Animal
MH  - Drug Synergism
MH  - Drug Therapy, Combination
MH  - Encephalomyelitis, Autoimmune, Experimental/*drug 
      therapy/immunology/physiopathology
MH  - Estradiol/metabolism/*pharmacology/therapeutic use
MH  - Female
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Multiple Sclerosis/*drug therapy/immunology/physiopathology
MH  - Myelin Basic Protein/drug effects/genetics/metabolism
MH  - Myelin Proteolipid Protein/drug effects/genetics/metabolism
MH  - Nerve Fibers, Myelinated/drug effects/metabolism/pathology
MH  - Neurosecretory Systems/*immunology
MH  - Progesterone/metabolism/*pharmacology/therapeutic use
MH  - RNA, Messenger/drug effects/metabolism
MH  - Sodium-Potassium-Exchanging ATPase/genetics
MH  - Treatment Outcome
MH  - Up-Regulation/drug effects/physiology
EDAT- 2008/08/01 09:00
MHDA- 2008/10/31 09:00
CRDT- 2008/08/01 09:00
PHST- 2008/08/01 09:00 [pubmed]
PHST- 2008/10/31 09:00 [medline]
PHST- 2008/08/01 09:00 [entrez]
AID - 000135627 [pii]
AID - 10.1159/000135627 [doi]
PST - ppublish
SO  - Neuroimmunomodulation. 2008;15(1):76-83. doi: 10.1159/000135627. Epub 2008 Jul 
      29.