%0 Journal Article
%T TLR4-mediated brain inflammation halts neurogenesis: impact of hormonal replacement therapy
%A Abdeslam Mouihate
%J Frontiers in Cellular Neuroscience
%D 2014
%I Frontiers Media
%R 10.3389/fncel.2014.00146
%X Experimental and epidemiological data show that the severity and the duration of brain inflammation are attenuated in females compared to males. This attenuated brain inflammation is ascribed to 17¦Â-estradiol. However, several studies suggest that 17¦Â-estradiol is also endowed with proinflammatory properties. The aim of the present study is to assess the effect of hormonal replacement therapies on lipopolysaccharide (LPS)-induced brain inflammation and its consequent effect on newly born neurons. Bilaterally ovariectomized rats received intrastriatal injection of LPS (250 ng/¦Ìl) and were subsequently given daily subcutaneous injections of either vehicle, 17¦Â-estradiol (25 ¦Ìg/kg) or 17¦Â-estradiol and progesterone (5 mg/kg). Microglial activation and newly born neurons in the rostral migratory stream were monitored using double immunofluorescence. Nuclear factor ¦ÊB (NF¦ÊB) signaling pathway and its target inflammatory proteins were assessed by either western blot [cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6)] or enzyme-linked immunosorbent assay [tumor necrosis factor-¦Á (TNF-¦Á)]. LPS-induced activation of microglia, promoted NF¦ÊB signaling pathway and enhanced the production of proinflammatory proteins (TNF-¦Á and COX-2). These proinflammatory responses were not attenuated by 17¦Â-estradiol injection. Supplementation of 17¦Â-estradiol with progesterone significantly dampened these proinflammatory processes. Interestingly, LPS-induced brain inflammation dampened the number of newly born neurons in the rostral migratory stream. Administration of combined 17¦Â-estradiol and progesterone resulted in a significantly higher number of newly born neurons when compared to those seen in rats given either vehicle or 17¦Â-estradiol alone. These data strongly suggest that combined 17¦Â-estradiol and progesterone, and not 17¦Â-estradiol alone, rescues neurogenesis from the deleterious effect of brain inflammation likely via the inhibition of the signaling pathways leading to the activation of proinflammatory genes.
%K microglia
%K TNF-¦Á
%K COX-2
%K doublecortin
%K NF¦ÊB
%K neuroprotection
%U http://www.frontiersin.org/Journal/10.3389/fncel.2014.00146/abstract