Avtor/Urednik		Luchetti, Sabina; Eden, Corbert G. van; Schuurman, Karianne; Strien, Miriam E. van; Swaab, Dick Frans; Huitinga, Inge
Naslov		Gender differences in multiple sclerosis
Tip		članek
Vol. in št.		Letnik 73, št. 2
Leto izdaje		2014
Obseg		str. 123-135
ISSN		0022-3069 - Journal of neuropathology and experimental neurology
Jezik		eng
Abstrakt		The basis of gender differences in the prevalence and clinicalprogression of multiple sclerosis (MS) is not understood. Here, weidentify gender-specific responses in steroid synthesis and signalingin the brains of MS patients as possible contributors to these differ-ences. We investigated gene expression changes in these pathwaysand of inflammatory cytokines in MS lesions and normal-appearingwhite matter (NAWM) of male and female patients (n = 21) andcontrol NAWM (n = 14) using quantitative polymerase chain reac-tion (25 MS lesions, 21 MS NAWM, and 14 control NAWM) andimmunohistochemistry (3Y4 sections per group). In MS lesions inmales, there was local upregulation of aromatase (an enzyme in-volved in estrogen biosynthesis), estrogen receptor-A(ERA), andtumor necrosis factor (TNF) mRNA; whereas in females, there waslocal upregulation of 3A-hydroxysteroid-dehydrogenase, a proges-terone synthetic enzyme, and of progesterone receptor. Astrocytes inthe rim and center of MS lesions were found to be the primary sourceof steroidogenic enzyme and receptor expression. Aromatase andER>mRNA levels were positively correlated with that of TNF inprimary cultures of human microglia and astrocytes; TNF causedincreased ER>, suggesting that inflammatory signals stimulate es-trogen signaling in this cell type. Together, these findings suggestthat there are gender differences in the CNS of MS patients that mayaffect lesion pathogenesis, that is, in males, estrogen synthesis andsignaling are induced; whereas in females, progestogen synthesis andsignaling are induced. These differences may represent contributingfactors to gender differences in the prevalence and course of MS.
Proste vsebinske oznake		gene expression multiple sclerosis neurosteroids genska ekspresija multipla skleroza nevrosteroidi