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García-Izquierdo Eusebio Moñivas-Palomero Vanessa Forteza Alberto Martín-López Carlos Torres-Sanabria Mario Cia-Mendioroz Xabier Olivo-Rodríguez Consuelo Navarro-Rico Sara Sánchez-Gómez Andrés Mirelis Jesús G. Cavero Miguel A. Mingo-Santos Susana 《The international journal of cardiovascular imaging》2021,37(9):2735-2745
The International Journal of Cardiovascular Imaging - Previous studies using conventional echocardiographic measurements have reported subclinical left ventricular (LV) diastolic abnormalities in... 相似文献
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Rosa AO Kaster MP Binfaré RW Morales S Martín-Aparicio E Navarro-Rico ML Martinez A Medina M García AG López MG Rodrigues AL 《Progress in neuro-psychopharmacology & biological psychiatry》2008,32(6):1549-1556
Glycogen synthase kinase-3beta (GSK-3beta) is an enzyme that phosphorylates glycogen synthase, thereby inhibiting glycogen synthesis. Besides this role, it is now believed that this enzyme plays an important role in the pathophysiology of many brain diseases including depression. Some inhibitors of this enzyme have shown antidepressant effects in animal models. This study investigated the effects of a novel thiadiazolidinone NP031115, a putative GSK-3beta inhibitor, and the well-established GSK-3beta inhibitor AR-A014418 in the mouse forced swimming test (FST), a model widely used to evaluate antidepressant activity. We found that NP031115 had an IC50 of 1.23 and 6.5 microM for GSK-3beta and GSK-3alpha, respectively. NP031115 (0.5 and 5 mg/kg, i.p.), in a way similar to imipramine (15 mg/kg, i.p), fluoxetine (32 mg/kg, i.p), AR-A014418 (9 mg/kg, i.p.), and rosiglitazone (5 microg/site, i.c.v.), significantly reduced immobility time in the FST. NP031115 at the higher dose and AR-A014418 (9 mg/kg, i.p.) reduced locomotion in the open-field test. Rosiglitazone (30 microM), AR-A014418 (1 microM), PG(J2) (10 microM), and NP031115 (1, 10 and 25 microM) activate PPARgamma in CHO transfected cells. GW-9662 (10 microg/site, i.c.v, a PPARgamma antagonist) administered 15 min before NP03115 (5 mg/kg, i.p.) or co-administered with rosiglitazone (5 microg/site, i.c.v.) prevented the antidepressant-like effect of these drugs in the FST. The results of this study show that NP031115 can exhibit an antidepressant effect, likely by inhibiting GSK-3beta and enhancing PPARgamma activity. 相似文献
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