Cannabidiol (CBD), a non-psychoactive cannabinoid, shows great promise in treating methamphetamine (METH) addiction. Nonetheless, the molecular target and the mechanism through which CBD treats METH addiction remain unexplored. Herein, CBD was shown to counteract METH-induced locomotor sensitization and conditioned place preference. Additionally, CBD mitigated the adverse effects of METH, such as cristae loss, a decline in ATP content, and a reduction in membrane potential. Employing an activity-based protein profiling approach, a target fishing strategy was used to uncover CBD's direct target. ATP5A1, a subunit of ATP synthase, was identified and validated as a CBD target. Moreover, CBD demonstrated the ability to ameliorate METH-induced ubiquitination of ATP5A1 via the D376 residue, thereby reversing the METH-induced reduction of ATP5A1 and promoting the assembly of ATP synthase. Pharmacological inhibition of the ATP efflux channel pannexin 1, blockade of ATP hydrolysis by a CD39 inhibitor, and blocking the adenosine A1 receptor (A1R) all attenuated the therapeutic benefits of CBD in mitigating METH-induced behavioral sensitization and CPP. Moreover, the RNA interference of ATP5A1 in the ventral tegmental area resulted in the reversal of CBD's therapeutic efficacy against METH addiction. Collectively, these data show that ATP5A1 is a target for CBD to inhibit METH-induced addiction behaviors through the ADO-A1R signaling pathway.

“Omics” is a integral thought, which can provide a non-bias method, identify the biochemical pathways of the diseases, and ultimately determine the target for future research. It includes genomics, transcriptomics, proteomics and metabonomics. We elaborate the cooperative development of omics in recent years and it’s role in the genetic variation in Parkinson's disease in this article.

Objective To determine whether a prophylactic tolterodine administration before surgical operation on non-urologic patients under general aneathesia can prevent the occurrence of catheter-related bladder discomfort (CRBD) ; and to assess patients’ tolerance to the symptoms as well as the impact on related consultation work of urologic surgeons.Methods One hundred and eighty cases of non-urology patients who need general aneathesia operations were divided into 2 groups:90 cases in tolterodine group and 90 in control group.The assessment of CRBD is categorized into 4 steps and statistics for adverse events ( dry mouth,dizzyness and facial flushing) was also conducted.A record of the patients’ needs for urologic surgical consultation during their reservation of catheter was also kept.SPSS 13.0 used in the statistical analysis of data in terms of X2 examination,where the divergence P ＜ 0.05 was regarded statisticly valid.Results 82 cases were followed up in the tolterodine group with a 24.4％ CRBD occurrence,which included 7.2％ shows moderate and severe symptoms,and there were also 23 cases with dry mouth ( 28.0％ ),4 cases with dizzyness (4.8％),13 cases with facial flussing ( 15.8％ ),and 1 case who needs further consultation (1.2％).In the 86 followed-up cases in control group,CRBD occurance rate was 54.7％,with 30.2％ showed moderate and severe symptoms,plus 2 cases suffered from severe consequences.Nine cases ( 10.5％) in control group requires further consultation ( X2 =19.499,P =0.000 ＜ 0.05 ).Conclusions A prophylactic tolterodine administration before surgery to the patients underwent general aneathesia can prevent the occurrence ofcatheter-related bladder discomfort (CRBD) and reduce the consultation work of urologic surgeons.Patients using tolterodine show a higher rate of adverse events,yet to which most patients can tolerate.

OBJECTIVE: To explore whether the Ad5-atoh1/EGFP could transdifferent the supporting cells into the new hair cells in young adult guinea pigs cochlea in vivo. METHOD: Twelve healthy pigmented guinea pigs weighted 200-250 g were included in this experiment. 5 ul of Ad5-E1/E3 defected-atoh1/EGFP were infused into the scala media through a hole made on the lateral wall of the cochlea. Six of the 12 animal were killed 2 weeks after the infusion operation. The others were killed 4 weeks after the operation. The whole mount of the basal membranes were directly observed under the fluorescence microscope for the expression of the EGFP (enhance green fluorescent protein) or for the expression of the hair cellspecific marker and nuclear after staining with myosin VIIa rabbit polyclonal antibody and Dapi dye. RESULT: New cells with big nuclear, ellipse body and expressed with EGFP were found in the region near to the outmost row of the outer hair cells in 2 animal 2 weeks after the infusion. Moreover there were 3 animals with specific morphologic new cells in the location where ever been located by the outer hair cells and the region as 2 weeks animals 4 weeks after the infusion. Those cells were stained by myosin VIIa antibody. CONCLUSION Atoh1 gene could transdifferent some supporting cells in the basal membrane into hair cell like cells in young adult guinea pigs in vivo. These supporting cells locate in the region of outer hair cells and the basal membrane which do not belong to the region of outer hair cells.
Animals ; Basic Helix-Loop-Helix Transcription Factors ; genetics ; metabolism ; Cell Transdifferentiation ; genetics ; Cochlea ; cytology ; Ear, Inner ; Green Fluorescent Proteins ; genetics ; metabolism ; Guinea Pigs ; Hair Cells, Auditory ; cytology ; Labyrinth Supporting Cells ; cytology

Objective To modify the method of gavage administration in guinea pigs. Methods Fourty awake guinea pigs were kept rearing on the hind legs and leaning on a vertical fixture to avoid their escaping forward. A 1 mL injector was inserted into the mouth to the depth when the molar teeth were passed. Another fourty guinea pigs under general anesthesia were reversed at trendelenburg position and a children suction tube with an outer diameter of 2 mm was inserted into the stomach. Results All of the 80 guinea pigs were administered by modified gavage smoothly for seven consecutive days by one operator each time. None endured much pain or digestive tract injury, or died from air way perfusion by mistake. Conclusions We successfully modified the gavage method in guinea pigs, which would definitely take guinea pigs involved in intragastical pharmacal experiments besides the routine of rats and mice.