Although our recent report demonstrates the essential involvement of IP3R-1 up-regulation induced by dopamine D1-like and D2-like receptor (D1 and D2R) stimulation in psychological dependence, exact regulatory mechanisms of IP3R-1 expression by D2Rs have not yet been clarified. Mouse cerebral cortical neurons were treated with inhibitor of Ca2+-related signal transduction pathways coupling to D2Rs and used to analyze the mechanisms of IP3R-1 expression regulated
by transcriptional factor. A selective D2R agonist, quinpirole, up-regulated IP3R-1 protein following its mRNA increase, which was significantly inhibited by gallein (a G beta gamma modulator), U73122 (a phospholipase C inhibitor), BAPTA-AM (an intracellular BMS-777607 in vivo find more calcium chelating reagent), W7 (a calmodulin inhibitor), KN-93 (a calmodulin-dependent protein kinases inhibitor), and FK506 (a calcineurin
inhibitor). Immunocytochemical assessment showed that quinpirole increased expression of both cFos and phosphorylated-cJun in nucleus and enhanced translocation of NFATc4 complex to nucleus from cytoplasm. In addition, quinpirole directly recruited bindings between AP-1 and IP3R-1 promoter region and between NFATc4 and IP3R-1 promoter region. These results indicate that D2Rs enhance IP3R-1 gene transcription via increased bindings of AP-1 and NFATc4 to IP3R-1 promoter region after G beta gamma activation. (C) 2013 Elsevier Ltd. All rights reserved.”
“Background: Over the last 15 years, bacterial meningitis has received considerable attention, including national guidelines, whilst viral central nervous system (CNS) infections have been relatively neglected. A recent pilot study suggested that management of patients with suspected Selleckchem Cyclosporin A viral encephalitis was often suboptimal.
Aim: To examine the relative incidence, clinical features and management of suspected acute CNS infections in adults across the NHS North West Region.
Design: A multicentre cross-sectional retrospective cohort study at 10 hospitals across the region over 3 months (from September to December 2007). Following a screen of all patients who had cerebrospinal fluid (CSF) analysis
or received intravenous aciclovir and/or third-generation cephalosporin, those with clinical features suspicious of a CNS infection were included. Management was compared with the national meningitis and regional encephalitis guidelines.
Results: Three hundred and eighty-five patients were screened; 217 patients had a suspected CNS infection and 44 (20%) had a CNS infection: 18 aseptic meningitis (one herpes simplex virus [HSV]-2), 13 purulent meningitis (four Streptococcus pneumoniae) and 13 encephalitis (three HSV-1). The median (range) time from admission to suspicion of CNS infection and to LP was longer for patients with encephalitis than meningitis [4 (0.3-312) vs. 0.3 (0.1-12) h, P < 0.001, and 23 (4-360) vs. 12 (2-48) h, P = 0.