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1.
J Neuroinflammation ; 14(1): 235, 2017 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-29202778

RESUMO

BACKGROUND: Multiple sclerosis (MS) is a demyelinating and degenerative disease of the central nervous system. Normally, demyelination is followed by remyelination, which requires repopulation of a demyelinated area by oligodendrocyte precursor cells. Although large numbers of precursor cells are present in MS lesions, remyelination often fails, in part by the inability of precursor cells to differentiate into mature myelin-forming cells. In mouse and rat, miR-219 is required for this differentiation. Previously, we identified decreased miR-219 expression in tissue of MS patients compared to controls. Cell-free miRNAs have been detected in many different body fluids including cerebrospinal fluid (CSF) and may reflect disease processes going on in the central nervous system. This prompted us to investigate the biomarker performance of CSF miR-219 for MS diagnosis. METHODS: Quantitative PCR was performed measuring miR-219 levels in CSF of MS patients and controls in three independent cohorts. RESULTS: All three cohorts of MS patients and controls revealed that absence of miR-219 detection in CSF is consistently associated with MS. CONCLUSIONS: We have been able to identify and validate absence of miR-219 detection in CSF of MS patients compared to controls, suggesting that it may emerge as a candidate biomarker for MS diagnosis.


Assuntos
Biomarcadores/líquido cefalorraquidiano , MicroRNAs/líquido cefalorraquidiano , Esclerose Múltipla/líquido cefalorraquidiano , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
2.
Psychoneuroendocrinology ; 84: 76-82, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28668711

RESUMO

Differences in hypothalamic-pituitary-adrenocortical (HPA) functioning between patients with posttraumatic stress disorder (PTSD) and controls are among the most consistent neurobiological findings in PTSD. HPA-axis activation results in the output of various steroid hormones including dehydroepiandrosterone (DHEA), which is then converted into dehydroepiandrosterone sulfate (DHEA-S), with anti-glucocorticoid actions among its pleiotropic effects. To investigate whether there is evidence for consistent differences in basal DHEA and DHEA-s levels between individuals with and without PTSD, we performed random-effect meta-analyses aggregating findings of previously published studies. Nine studies reporting on DHEA levels (486 participants) and 8 studies reporting on DHEA-S levels (501 participants) were included. No significant differences in DHEA or DHEA-S levels between PTSD and control groups were found. Exploratory subgroup analyses were performed to distinguish between effects of PTSD and trauma exposure. A trend for higher DHEA levels was found in PTSD patients compared to non-trauma-exposed controls (NTC) (k=3, SMD=1.12 95% CI -0.03-2.52, Z=1.91, p=0.06). Significantly higher DHEA-S levels were observed in PTSD patients compared to NTC (k=2, SMD=0.76, 95% CI 0.38-1.13, Z=3.94, p<0.001). Additionally, significantly higher DHEA levels were observed in trauma-exposed controls (TC) compared to NTC (k=3, SMD=0.66, 95% CI 0.33-0.99, Z=3.88, p<0.001, I2=86%) this suggests that trauma exposure, irrespective of further PTSD development, might increase basal DHEA and DHEA-S levels.


Assuntos
Sulfato de Desidroepiandrosterona/análise , Desidroepiandrosterona/análise , Transtornos de Estresse Pós-Traumáticos/metabolismo , Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona/sangue , Feminino , Glucocorticoides/metabolismo , Humanos , Hidrocortisona/análise , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Sistema Hipófise-Suprarrenal/metabolismo
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