ABSTRACT
Malfunction of the ventral subiculum (vSub), the main subregion controlling the output connections from the hippocampus, is associated with major depressive disorder (MDD). Although the vSub receives cholinergic innervation from the medial septum and diagonal band of Broca (MSDB), whether and how the MSDB-to-vSub cholinergic circuit is involved in MDD is elusive. Here, we found that chronic unpredictable mild stress (CUMS) induced depression-like behaviors with hyperactivation of vSub neurons, measured by c-fos staining and whole-cell patch-clamp recording. By retrograde and anterograde tracing, we confirmed the dense MSDB cholinergic innervation of the vSub. In addition, transient restraint stress in CUMS increased the level of ACh in the vSub. Furthermore, chemogenetic stimulation of this MSDB-vSub innervation in ChAT-Cre mice induced hyperactivation of vSub pyramidal neurons along with depression-like behaviors; and local infusion of atropine, a muscarinic receptor antagonist, into the vSub attenuated the depression-like behaviors induced by chemogenetic stimulation of this pathway and CUMS. Together, these findings suggest that activating the MSDB-vSub cholinergic pathway induces hyperactivation of vSub pyramidal neurons and depression-like behaviors, revealing a novel circuit underlying vSub pyramidal neuronal hyperactivation and its associated depression.
Subject(s)
Rats , Mice , Animals , Rats, Sprague-Dawley , Depressive Disorder, Major/metabolism , Basal Forebrain , Depression , Hippocampus/metabolism , Cholinergic AgentsABSTRACT
Objective@#To evaluate the effect of functional training on the improvement of Cobb Angle, ATR and quality of life in adolescent idiopathic scoliosis.@*Methods@#Database of CNKI, WanFang, WeiPu, Web of Science, PubMed were reconnoitered for the purpose of research articles of Interest. Literature was screened according to the inclusion criteria, randomized controlled trials (RCTS) were collected and Cochrane risk bias assessment methodology quality was used, and Revman 5.3 software was used to conduct combined effector subgroup analysis on outcome indicators (Cobb Angle, ATR, SRS-22 patient questionnaire).@*Results@#A total of 10 RCT (398 AIS patients) were included in the study. There were two high , five moderate and three low quality studies, respectively. Compared with other non operative treatments, functional training could reduce Cobb horn in patients, MD = -6.56 (95% CI =-7.30--5.83, P <0.01, I 2=0). Further subgroup analysis showed that there were no statistically significant differences in effect size between the subgroups of Cobb Angle, age, intervention period and control method at the time of inclusion ( P >0.05). Compared with the non intervention blank group, the functional training group could reduce the Cobb Angle of patients ( MD = -5.25 , 95% CI =-8.27- -2.98 , P < 0.01 ), with high heterogeneity ( I 2=61%). Effect on angle of trunk rotation(ATR):functional training group could reduce patients ATR, MD =-1.91 (95% CI =-2.25--1.57, P <0.01, I 2=0). The impact on the quality of life:functional training of patients with SRS-22 questionnaire function, pain had no statistical significance ( P >0.05), and self image ( MD =0.64, 95% CI =0.53- 0.75 , P <0.01), mental health ( MD =0.44, 95% CI =0.15-0.74, P <0.01), satisfaction ( MD = 0.58 , 95% CI =0.11- 1.06 , P = 0.02 ) were statistically significant.@*Conclusion@#Functional training can not only reduce the Cobb Angle and ATR of AIS patients, but also improve the quality of life in terms of self image, mental health and satisfaction of the patients. However, due to heterogeneity and bias, more high quality studies are needed to verify.
ABSTRACT
OBJECTIVE@#To discover the relationship of transcriptional levels and promoter methylation status of CHFR gene in human nasopharyngeal carcinoma,to discuss the significance and epigenetic mechanism of CHFR inactivation in NPC, and to evaluate the feasibility of detecting methylated CHFR in nasopharyngeal swab as a means for diagnosis of NPC.@*METHOD@#Transcriptional levels of CHFR was evaluated by RT-PCR. Methylation specific PCR was used to detect the methylation status of CHFR in NPC cells, normal nasopharyngeal epithelia, primary tumors and their paired nasopharyngeal swabs. Detailed methylation status was confirmed by bisulfite sequencing. NPC cells were treated by the methyltransferase inhibitor 5-aza-dC and the reactivation of CHFR was evaluated by RT-PCR.@*RESULT@#CHFR transcription was inactivated in NPC. The methylation frequency in NPC primary tumors and their paired swabs were 65.5% and 63.8%, respectively, with a 86.2% concordance. Bisulfite sequencing revealed a dense methylation in NPC cells and primary tumors, but all the normal nasopharyngeal epithelia were unmethylated. CHFR expression were restored after 5-aza-dC treatment.@*CONCLUSION@#CHFR is epigenetically inactivated by promoter methylation in NPC. Detecting methylated CHFR can be served as a useful non-invasive means for diagnosis of NPC.