PMC:5118426 / 36669-38816 JSONTXT

{"project":"MyTest","denotations":[{"id":"27920719-22880010-31054393","span":{"begin":179,"end":183},"obj":"22880010"},{"id":"27920719-22155097-31054394","span":{"begin":765,"end":769},"obj":"22155097"},{"id":"27920719-20665558-31054395","span":{"begin":1148,"end":1152},"obj":"20665558"},{"id":"27920719-22416216-31054396","span":{"begin":1468,"end":1472},"obj":"22416216"},{"id":"27920719-22361233-31054397","span":{"begin":1759,"end":1763},"obj":"22361233"},{"id":"27920719-15190125-31054398","span":{"begin":2141,"end":2145},"obj":"15190125"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"Modulation of neurotransmitter activity\nThe wake period of normal mice was found to be increased with administration of UDCA that also decreased slow wave sleep (Yanovsky et al., 2012). In contrast, administration of UDCA to histidine decarboxylase knockout mice, that are deficient in histamine that stimulates arousal, decreased wakefulness and altered cortical EEG and sleep-wake parameters. Using in vitro patch-clamp recordings from histaminergic neurons, UDCA was found to inhibit GABAergic currents and to serve as an antagonist for GABAA receptors expressed in HEK293 cells. In one of the few studies to analyze more than one or two bile acids, a structure-function relationship analysis was performed using cultured hypothalamic neurons (Schubring et al., 2012). Bile acids were found to modulate firing frequency and synchrony, and to block activity of GABAA and NMDA receptors. Antagonist activity for both the GABAA and NMDA receptors was strongest for CDCA followed by DCA, CA, and dehydrocholate. Involvement of bile acid binding to TGR5 was excluded as a potential mechanism in the neurotransmitter receptor blockade (Keitel et al., 2010).\nCA was found to serve as an inhibiter for N-type Ca2+ channel currents of neurons isolated from the caudal paravertebral sympathetic ganglia of adult bull frogs (Rana catesbeiana), although open and shut times, slope conductance, and single channel current amplitude, were not significantly affected (Lee et al., 2012). Overstimulation of glutamate receptors to induce excitotoxicity in neurons isolated from late stage fetal rat brains was largely suppressed by GUDCA. This bile acid appeared to suppress glutamate release in either normal or microglia-depleted hippocampal tissue slices (Silva et al., 2012). Pretreatment of primary cultures of fetal rat cortical neurons with TUDCA significantly reduced glutamate excitotoxicity associated cell death. TUDCA treatment resulted in phosphorylation and translocation of the pro-apoptotic Bad protein from the mitochondria to the cytosol. Inhibiting the PI3K signaling pathway blocked the anti-apoptotic effects of TUDCA (Castro et al., 2004)."}

{"project":"2_test","denotations":[{"id":"27920719-22880010-31054393","span":{"begin":179,"end":183},"obj":"22880010"},{"id":"27920719-22155097-31054394","span":{"begin":765,"end":769},"obj":"22155097"},{"id":"27920719-20665558-31054395","span":{"begin":1148,"end":1152},"obj":"20665558"},{"id":"27920719-22416216-31054396","span":{"begin":1468,"end":1472},"obj":"22416216"},{"id":"27920719-22361233-31054397","span":{"begin":1759,"end":1763},"obj":"22361233"},{"id":"27920719-15190125-31054398","span":{"begin":2141,"end":2145},"obj":"15190125"}],"text":"Modulation of neurotransmitter activity\nThe wake period of normal mice was found to be increased with administration of UDCA that also decreased slow wave sleep (Yanovsky et al., 2012). In contrast, administration of UDCA to histidine decarboxylase knockout mice, that are deficient in histamine that stimulates arousal, decreased wakefulness and altered cortical EEG and sleep-wake parameters. Using in vitro patch-clamp recordings from histaminergic neurons, UDCA was found to inhibit GABAergic currents and to serve as an antagonist for GABAA receptors expressed in HEK293 cells. In one of the few studies to analyze more than one or two bile acids, a structure-function relationship analysis was performed using cultured hypothalamic neurons (Schubring et al., 2012). Bile acids were found to modulate firing frequency and synchrony, and to block activity of GABAA and NMDA receptors. Antagonist activity for both the GABAA and NMDA receptors was strongest for CDCA followed by DCA, CA, and dehydrocholate. Involvement of bile acid binding to TGR5 was excluded as a potential mechanism in the neurotransmitter receptor blockade (Keitel et al., 2010).\nCA was found to serve as an inhibiter for N-type Ca2+ channel currents of neurons isolated from the caudal paravertebral sympathetic ganglia of adult bull frogs (Rana catesbeiana), although open and shut times, slope conductance, and single channel current amplitude, were not significantly affected (Lee et al., 2012). Overstimulation of glutamate receptors to induce excitotoxicity in neurons isolated from late stage fetal rat brains was largely suppressed by GUDCA. This bile acid appeared to suppress glutamate release in either normal or microglia-depleted hippocampal tissue slices (Silva et al., 2012). Pretreatment of primary cultures of fetal rat cortical neurons with TUDCA significantly reduced glutamate excitotoxicity associated cell death. TUDCA treatment resulted in phosphorylation and translocation of the pro-apoptotic Bad protein from the mitochondria to the cytosol. Inhibiting the PI3K signaling pathway blocked the anti-apoptotic effects of TUDCA (Castro et al., 2004)."}