國家衛生研究院 NHRI:Item 3990099045/8403
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    題名: Methamphetamine induces a rapid increase of intracellular Ca++ levels in neurons overexpressing GCaMP5
    作者: Yu, SJ;Wu, KJ;Bae, EK;Hsu, MJ;Richie, CT;Harvey, BK;Wang, Y
    貢獻者: Center for Neuropsychiatric Research
    摘要: In this study, methamphetamine (Meth)- and glutamate (Glu)-mediated intracellular Ca++ (Ca++ i) signals were examined in real time in primary cortical neurons overexpressing an intracellular Ca++ probe, GCaMP5, by adeno-associated viral (AAV) serotype 1. Binding of Ca++ to GCaMP increased green fluorescence intensity in cells. Both Meth and Glu induced a rapid increase in Ca++ i, which was blocked by MK801, suggesting that Meth enhanced Ca++ i through Glu receptor in neurons. The Meth-mediated Ca++ signal was also blocked by Mg++ , low Ca++ or the L-type Ca++ channel inhibitor nifedipine. The ryanodine receptor inhibitor dantrolene did not alter the initial Ca++ influx but partially reduced the peak of Ca++ i. These data suggest that Meth enhanced Ca++ influx through membrane Ca++ channels, which then triggered the release of Ca++ from the endoplasmic reticulum in the cytosol. AAV-GCaMP5 was also injected to the parietal cortex of adult rats. Administration of Meth enhanced fluorescence in the ipsilateral cortex. Using immunohistochemistry, Meth-induced green fluorescence was found in the NeuN-containing cells in the cortex, suggesting that Meth increased Ca++ in neurons in vivo. In conclusion, we have used in vitro and in vivo techniques to demonstrate a rapid increase of Ca++ i by Meth in cortical neurons through overexpression of GCaMP5. As Meth induces behavioral responses and neurotoxicity through Ca++ i, modulation of Ca++ i may be useful to reduce Meth-related reactions.
    日期: 2016-03
    關聯: Addiction Biology. 2016 Mar;21(2):255-266.
    Link to: http://dx.doi.org/10.1111/adb.12193
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1355-6215&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000371148700004
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84959343991
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