Progesterone treatment reduces disease severity and increases IL-10 in experimental autoimmune encephalomyelitis

Yates, Melissa A.; Li, Y.; Chlebeck, Peter J.; Proctor, Thomas M.; Vandenbark, Arthur A.; Offner, Halina

doi:10.1016/j.jneuroim.2010.01.013

Cited by 109 publications

(78 citation statements)

References 41 publications

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“…In the same animal model, other evidences report that PROG was able to reduce inflammatory markers (i.e. microglia activation, IL1b, IL2, and IL17) (Yates et al 2010, Giatti et al 2012.…”

Section: Neuroactive Steroids As Neuroinflammatory Modulatorsmentioning

confidence: 75%

Neuroactive steroids, their metabolites, and neuroinflammation

Giatti¹,

Boraso²,

Melcangi³

et al. 2012

Journal of Molecular Endocrinology

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Neuroinflammation represents a common feature of many neurodegenerative diseases implicated both in their onset and progression. Neuroactive steroids act as physiological regulators and protective agents in the nervous system. Therefore, the attention of biomedical research has been recently addressed in evaluating whether neuroactive steroids, such as progestagens, androgens, and estrogens may also affect neuroinflammatory pathways. Observations so far obtained suggest a general anti-inflammatory effect with a beneficial relapse on several neurodegenerative experimental models, thus confirming the potentiality of a neuroprotective strategy based on neuroactive steroids. In this scenario, neuroactive steroid metabolism and the sophisticated machinery involved in their signaling are becoming especially attractive. In particular, because metabolism of neuroactive steroids as well as expression of their receptors is affected during the course of neurodegenerative events, a crucial role of progesterone and testosterone metabolites in modulating neuroinflammation and neurodegeneration may be proposed. In the present review, we will address this issue, providing evidence supporting the hypothesis that the efficacy of neuroactive steroids could be improved through the use of their metabolites.

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“…In the same animal model, other evidences report that PROG was able to reduce inflammatory markers (i.e. microglia activation, IL1b, IL2, and IL17) (Yates et al 2010, Giatti et al 2012.…”

Section: Neuroactive Steroids As Neuroinflammatory Modulatorsmentioning

confidence: 75%

Neuroactive steroids, their metabolites, and neuroinflammation

Giatti¹,

Boraso²,

Melcangi³

et al. 2012

Journal of Molecular Endocrinology

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“…All oestrogens are not exactly alike [5,23]. Importantly and unlike 17β-oestradiol, the common oestrogen found in pills ethynil oestradiol [24,25] and progesterone [26] reduce the clinical severity of EAE when given after the onset of disease signs. Because the large majority of our patients have used different combinations of ethynil oestradiol and a progestogen, we cannot exclude that these hormones could have different impacts on the observed protective effects.…”

Section: P-valuementioning

confidence: 99%

Oral contraceptive use and clinical outcomes in patients with multiple sclerosis

Sena¹,

Couderc²,

Vasconcelos³

et al. 2012

Journal of the Neurological Sciences

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Experimental and clinical data suggest a role of sex steroids in the pathogenesis of multiple sclerosis (MS). Scant information is available about the potential effect of oral contraceptive (OC) use on the prognosis of the disease. We aimed to evaluate this. The study population consisted of 132 women with relapsing-remitting MS before receiving disease modifying treatment and a mean disease duration 6.2 (SD 5.1) years. Three groups of patients were distinguished according to their OC behavior: [1] never-users, patients who never used OC [2] past-users, patients who stopped OC use before disease onset, and [3] after-users, those who used these drugs after disease onset. Multiple linear and logistic regression models were used to analyze the association between oral contraceptive use and annualized relapse rates, disability accumulation and severity of the disease. After-user patients had lower Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) values than never users (p b 0.001 and p = 0.002, respectively) and past users (p = 0.010 and p = 0.002, respectively). These patients were also more likely to have a benign disease course (MSSS b 2.5) than never and past users together (OR: 4.52, 95%CI: 2.13-9.56, p b 0.001). This effect remained significant after adjustment for confounders, including smoking and childbirths (OR: 2.97, 95%CI: 1.24, 6.54, p = 0.011 and for MSSS β: − 1.04; 95% C.I. − 1.78, − 0.30, p = 0.006). These results suggest that OC use in women with relapsing-remitting MS is possible associated with a milder disabling disease course.

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“…In human MS patients, neurosteroid levels were significantly reduced in the brain white matter, a finding that was consistent in EAE disease model in mice (Noorbakhsh et al 2011). Therapeutic use of steroids has decreased the severity of EAE in animal models (Yates et al 2010, Yu et al 2010. TSPO upregulation is observed in microglia, infiltrating macrophages and astrocytes in response to injury/ inflammatory insults (Cosenza-Nashat et al 2009).…”

Section: Neurosteroids and Multiple Sclerosis Pathogenesismentioning

confidence: 62%

Current status and future perspectives: TSPO in steroid neuroendocrinology

Selvaraj

2016

Journal of Endocrinology

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The mitochondrial translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), has received significant attention both as a diagnostic biomarker and as a therapeutic target for different neuronal disease pathologies. Recently, its functional basis believed to be mediating mitochondrial cholesterol import for steroid hormone production has been refuted by studies examining both in vivo and in vitro genetic Tspo-deficient models. As a result, there now exists a fundamental gap in the understanding of TSPO function in the nervous system, and its putative pharmacology in neurosteroid production. In this review, we discuss several recent findings in steroidogenic cells that are in direct contradiction to previous studies, and necessitate a re-examination of the purported role for TSPO in de novo neurosteroid biosynthesis. We critically examine the pharmacological effects of different TSPObinding drugs with particular focus on studies that measure neurosteroid levels. We highlight the basis of key misconceptions regarding TSPO that continue to pervade the literature, and the need for interpretation with caution to avoid negative impacts. We also summarize the emerging perspectives that point to new directions that need to be investigated for understanding the molecular function of TSPO, only after which the true potential of this therapeutic target in medicine may be realized.

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Progesterone treatment reduces disease severity and increases IL-10 in experimental autoimmune encephalomyelitis

Cited by 109 publications

References 41 publications

Neuroactive steroids, their metabolites, and neuroinflammation

Neuroactive steroids, their metabolites, and neuroinflammation

Oral contraceptive use and clinical outcomes in patients with multiple sclerosis

Current status and future perspectives: TSPO in steroid neuroendocrinology

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