Adenosine-regulated glutamate signaling in astrocytes is implicated in many neurological and neuropsychiatric disorders. In this study, we examined whether adenosine A1 receptor regulates EAAT2 expression in astrocytes using pharmacological agents and siRNAs. We found that adenosine A1 receptor-specific antagonist DPCPX or PSB36 decreased EAAT2 expression in a dose-dependent manner. Consistently, knockdown of A1 receptor in astrocytes decreased EAAT2 mRNA expression while overexpression of A1 receptor upregulated EAAT2 expression and function. Since A1 receptor activation is mainly coupled to inhibitory G-proteins and inhibits the activity of adenylate cyclase, we investigated the effect of forskolin, which activates adenylate cyclase activity, on EAAT2 mRNA levels. Interestingly, we found that forskolin reduced EAAT2 expression in dose- and time-dependent manners. In contrast, adenylate cyclase inhibitor SQ22536 increased EAAT2 expression in dose- and time-dependent manners. In addition, forskolin blocked ethanol-induced EAAT2 upregulation. Taken together, these results suggest that A1 receptor-mediated signaling regulates EAAT2 expression in astrocytes.
Purpose The exact correlation between the baseline left atrial (LA) volume (LAV) and atrial fibrillation (AF) radiofrequency catheter ablation (RFCA) outcomes and changes to the LA after AF RFCA has not yet been fully understood. We sought to evaluate the serial changes in the LAV and LA function after RFCA using 3D echocardiography. Methods Consecutive patients who received RFCA of paroxysmal (PAF) or persistent AF (PeAF) at our center between January 2013 and March 2016 were included. Real-time 3D apical full-volume images were acquired, and a 3D volumetric assessment was performed using an automated three-beat averaging method. The LAV index (LAVI) was calculated and the LA ejection fraction (LAEF) was calculated as [LAVmax − LAVmin]/LAVmax. Results Ninety-nine total patients were enrolled, and the mean age was 58.0 ± 8.2 years and 75 (74.7%) were male. There were 59 (59.6%) PAF patients and the remaining 40 (40.4%) had PeAF. AF recurred in 5 of 59 (8.5%) PAF and in 10 of 40 (25%) PeAF patients. The LAVImax increased on 1 day, decreased at 3 months, and then increased again at 1 year but was lower than that at baseline. The LAEF changes were similar to the volume changes but were more prominent in PeAF than PAF patients. The baseline 3D LAVImax was an independent predictor of AF recurrence after RFCA and the cut-off value was 44.13 ml/m 2 . Conclusion In our study, even after 3 months of scar formation due to ablation, structural remodeling of the LA continued. The changes were more prominent in the non-recurrent, PeAF patients.
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