Objective To observe the effect of adenosine A1 receptor (A1AR) on the megalin defect in type 1 diabetic mice with early kidney disease.Methods 7-8 week-old,baseline body weight and fasting blood glucose matched wild type (WT) C57BL/6J mice were selected,and randomly divided into two groups:control group (n=6) and WT DM group (n=6).In the same way,male A1AR knock-out C57BL/6J mice were selected as A1AR-/-DM group (n=6).DM model was established by intraperitoneal injection of streptozocin.The blood glucose (BG),body weight (BW),kidney weight (KW),24 h proteinuria (24hUP) and albumin creatine ratio (ACR) were measured at 4 weeks.The renal pathological lesion was observed and the expression of megalin in proximal tubules was examined by immunohistochemistry.The expression of caspase-1,IL-18 and A1AR were detected by Western blotting.Results At 4th week,compared with WT control mice,the BG,BW,KW and 24hUP of WT DM mice were increased significantly (n=6,P ＜ 0.01),with the pathological glomerular enlargement,mesangial cell proliferation,extracellular matrix accumulation and renal tubule hypertrophy being observed.Immunohistochemistry revealed decreased expression of megalin,an important multiligand protein receptor on the brush border of proximal tubular epithelial cells in WT DM mice,which was correlated with 24hUP (r=-0.645,P ＜ 0.01).Compared with the control mice,the expressions of caspase-1,IL-18 and A1AR were significantly increased in WT DM mice (P ＜ 0.05).For A1AR-/-DM mice,more serious pathological lesion and megalin defect,together with increasing of casapase-1 and heavier proteinuria were observed than those in WT DM mice.Conclusion A1AR may play a protective role in megalin expression of diabetic mice with early kidney disease,in which the mechanism may be associated with caspase-1 related pyroptosis pathway.The details need further exploration.

Motor timing is an important part of sensorimotor control. Previous studies have shown that beta oscillations embody the process of temporal perception in explicit timing tasks. In contrast, studies focusing on beta oscillations in implicit timing tasks are lacking. In this study, we set up an implicit motor timing task and found a modulation pattern of beta oscillations with temporal perception during movement preparation. We trained two macaques in a repetitive visually-guided reach-to-grasp task with different holding intervals. Spikes and local field potentials were recorded from microelectrode arrays in the primary motor cortex, primary somatosensory cortex, and posterior parietal cortex. We analyzed the association between beta oscillations and temporal interval in fixed-duration experiments (500 ms as the Short Group and 1500 ms as the Long Group) and random-duration experiments (500 ms to 1500 ms). The results showed that the peak beta frequencies in both experiments ranged from 15 Hz to 25 Hz. The beta power was higher during the hold period than the movement (reach and grasp) period. Further, in the fixed-duration experiments, the mean power as well as the maximum rate of change of beta power in the first 300 ms were higher in the Short Group than in the Long Group when aligned with the Center Hit event. In contrast, in the random-duration experiments, the corresponding values showed no statistical differences among groups. The peak latency of beta power was shorter in the Short Group than in the Long Group in the fixed-duration experiments, while no consistent modulation pattern was found in the random-duration experiments. These results indicate that beta oscillations can modulate with temporal interval in their power mode. The synchronization period of beta power could reflect the cognitive set maintaining working memory of the temporal structure and attention.