TRANSCRIPTOME ANALYSIS OF AMOEBOID AND RAMIFIED MICROGLIA ISOLATED FROM THE CORPUS CALLOSUM OF RAT BRAIN

Ph.DDOCTOR OF PHILOSOPH

Dexamethasone inhibits the Nox-dependent ROS production via suppression of MKP-1-dependent MAPK pathways in activated microglia

<p>Abstract</p> <p>Background</p> <p>Nox-2 (also known as gp91<it>phox</it>), a subunit component of NADPH oxidases, generates reactive oxygen species (ROS). Nox-dependent ROS generation and nitric oxide (NO) release by microglia have been implicated in a variety of diseases in the central nervous system. Dexamethasone (Dex) has been shown to suppress the ROS production, NO release and inflammatory reaction of activated microglial cells. However, the underlying mechanisms remain unclear.</p> <p>Results</p> <p>The present study showed that the increased ROS production and NO release in activated BV-2 microglial cells by LPS were associated with increased expression of Nox-2 and iNOS. Dex suppressed the upregulation of Nox-2 and iNOS, as well as the subsequent ROS production and NO synthesis in activated BV-2 cells. This inhibition caused by Dex appeared to be mediated by upregulation of MAPK phosphatase-1 (MKP-1), which antagonizes the activity of mitogen-activated protein kinases (MAPKs). Dex induced-suppression of Nox-2 and -upregulation of MKP-1 was also evident in the activated microglia from corpus callosum of postnatal rat brains. The overexpression of MKP-1 or inhibition of MAPKs (by specific inhibitors of JNK and p38 MAPKs), were found to downregulate the expression of Nox-2 and iNOS and thereby inhibit the synthesis of ROS and NO in activated BV-2 cells. Moreover, Dex was unable to suppress the LPS-induced synthesis of ROS and NO in BV-2 cells transfected with MKP-1 siRNA. On the other hand, knockdown of Nox-2 in BV-2 cells suppressed the LPS-induced ROS production and NO release.</p> <p>Conclusion</p> <p>In conclusion, it is suggested that downregulation of Nox-2 and overexpression of MKP-1 that regulate ROS and NO may form the potential therapeutic strategy for the treatment of neuroinflammation in neurodegenerative diseases.</p

Scutellarin regulates microglia-mediated TNC1 astrocytic reaction and astrogliosis in cerebral ischemia in the adult rats

Additional file 1: (A). Scutellarin at 0.54 mM did not elicit a noticeable reaction of GFAP/iNOS in TNC1. (B). iNOS mRNA expression in TNC1 astrocytes remained relatively unchanged at all time-points following treatment with BM, BM + L and CM; however, when incubated with CM + L for various time points, TNC1 showed a remarkable increase in iNOS peaking at 24 h. (C). Confocal images showing iNOS (C1-3) expression in TNC1 astrocytes incubated with different medium for 24 h. Compared with cells incubated in BM (C1) and BM + L (C2), TNC1 astrocytes incubated with CM + L (C3) were hypertrophic and showed a marked increase in iNOS immunofluorescence. Scale bars: 20 μm. DAPI—blue

Role of microglia in long-term potentiation and synaptic tagging/capture

Neuroscience 2016United State

Scutellarin regulates the Notch pathway and affects the migration and morphological transformation of activated microglia in experimentally induced cerebral ischemia in rats and in activated BV-2 microglia

10.1186/s12974-014-0226-zJournal of Neuroinflammation12

Differential gene expression profiles during embryonic heart development in diabetic mice pregnancy

10.1016/j.gene.2012.12.071GENE5162218-227NETHERLAND