Jun Cao

Ion channel mechanism and ingredient bases of Shenfu Decoction's cardiac electrophysiological effects

AIM OF THE STUDY Ion channel mechanism of cardiac electrophysiological effects of Shenfu Decoction (SFD, Ginseng and Aconiti Praeparatae Decoction), a traditional Chinese medicine (TCM) prescription, and its ingredient bases were investigated in guinea pigs. MATERIALS AND METHODS After administration of an injection made from SFD (Shenfu Injection, SFI), the indexes of transmembrane action potential (TAP) in vivo and sodium channels in isolated ventricular myocyte were assayed by suspended microelectrodes and patch clamp techniques respectively, and ingredients of SFD were compared with. RESULTS After administration of SFI, the action potential amplitude (APA) and maximum velocity (V(max)) of TAP decreased. In the presence of either SFI or Fuzi active ingredient (FZAI)(5, 10, and 15%), not any other ingredient, the density of voltage-dependent sodium current (I(Na)) decreased significantly, while the inhibition ratio of SFI was larger. EC(50) of SFI was less than the one of FZAI, and SFI displayed effects on I(Na) in wider voltage scope than FZAI in current-voltage curve. Both SFI and FZAI shifted the steady-state inactivation curve of sodium channels to the left, and the recovery curve to the right. CONCLUSIONS The results indicated that the cardiac electrophysiological effects of SFI were exerted by blocking sodium channels, and FZAI contributed to such effects most but inferior to SFI, which justified its use in anti-arrhythmia, myocardial protection, etc.

Abnormal regional homogeneity in young adult suicide attempters with no diagnosable psychiatric disorder: A resting state functional magnetic imaging study

Many young adults who attempt suicide have no discernible mental illness, suggesting an etiology distinct from other psychiatric disorders. Neurological anomalies associated with a history of suicidal behavior may predict future risk. In the present study, we explored changes in neural circuit organization associated with suicidal behavior by comparing local synchronization of resting-state functional magnetic resonance imaging signals in suicide attempters without a psychiatric diagnosis (SA group, 19.84±1.61 years, n=19) with those in healthy controls (HC group, 20.30±1.72 years, n=20) using regional homogeneity (ReHo) analysis. The SA group exhibited significantly lower mean ReHo in the left (L) fusiform and supraorbital inferior frontal gyri, L hippocampus, bilateral parahippocampal and middle frontal gyri, right (R) angular gyrus, and cerebellar lobules RVIII, RII, and LVI compared with the HC group. Conversely, in the SA group, ReHo was higher in the R supraorbital middle frontal gyrus, R inferior parietal lobe, and L precuneus. The SA group also had significantly higher total Barratt Impulsiveness Scale scores compared with the HC group. Local functional connectivity is altered in multiple regions of the cerebral cortex, limbic system, and cerebellum of suicidal young adults. Elucidating the functional deficits associated with these ReHo changes may clarify the pathophysiological mechanisms of suicidal behavior and assist in identifying high-risk individuals.

Propofol prevents electroconvulsive-shock-induced memory impairment through regulation of hippocampal synaptic plasticity in a rat model of depression.

Background Although a rapid and efficient psychiatric treatment, electroconvulsive therapy (ECT) induces memory impairment. Modified ECT requires anesthesia for safety purposes. Although traditionally found to exert amnesic effects in general anesthesia, which is an inherent part of modified ECT, some anesthetics have been found to protect against ECT-induced cognitive impairment. However, the mechanisms remain unclear. We investigated the effects of propofol (2,6-diisopropylphenol) on memory in depressed rats undergoing electroconvulsive shock (ECS), the analog of ECT in animals, under anesthesia as well as its mechanisms. Methods Chronic unpredictable mild stresses were adopted to reproduce depression in a rodent model. Rats underwent ECS (or sham ECS) with anesthesia with propofol or normal saline. Behavior was assessed in sucrose preference, open field and Morris water maze tests. Hippocampal long-term potentiation (LTP) was measured using electrophysiological techniques. PSD-95, CREB, and p-CREB protein expression was assayed with Western blotting. Results Depression induced memory damage, and downregulated LTP, PSD-95, CREB, and p-CREB; these effects were exacerbated in depressed rats by ECS; propofol did not reverse the depression-induced changes, but when administered in modified ECS, propofol improved memory and reversed the downregulation of LTP and the proteins. Conclusion These findings suggest that propofol prevents ECS-induced memory impairment, and modified ECS under anesthesia with propofol improves memory in depressed rats, possibly by reversing the excessive changes in hippocampal synaptic plasticity. These observations provide a novel insight into potential targets for optimizing the clinical use of ECT for psychiatric disorders.

Pharmacodynamic changes with vecuronium in sepsis are associated with expression of α7- and γ-nicotinic acetylcholine receptor in an experimental rat model of neuromyopathy

BACKGROUND Resistance to non-depolarizing neuromuscular blocking agents induced by sepsis is associated with the qualitative change in the nicotinic acetylcholine receptor (nAChR). This study aims to investigate the effects of sepsis on the neuromuscular block properties of vecuronium in relation to the expression of fetal and neuronal α7 type nAChR. METHODS Male Sprague-Dawley rats were randomly divided into sham and sepsis groups. Sepsis was induced by caecal ligation and puncture (CLP). The rats were injected i.v. with ulinastatin or normal saline on Day 10. Neuromuscular block properties of vecuronium were evaluated and neuromuscular function was assessed by electromyography on Days 1, 3, 7, and 14 after CLP. Expression of fetal and neuronal type α7-nAChR on the tibialis anterior muscle was assessed using immunohistochemistry and western blot. The mRNA encoding for γ- and α7 subunits was evaluated by real-time polymerase chain reaction. RESULTS The half maximal inhibitory response of vecuronium in the sepsis group significantly increased, peaked on Day 7, and then declined on Day 14 (P<0.05). The neuromuscular function decreased with increasing postoperation time in the sepsis group (P<0.05). Sepsis significantly increased the expression of γ- and α7-nAchR along with expression of γ- and α7 subunits mRNA, peaked on Day 7, and declined on Day 14 (P<0.05). Ulinastatin suppressed the expression of receptor protein and mRNA encoding for γ- and α7 subunits (P<0.05). CONCLUSIONS Pharmacodynamic changes with vecuronium seem to be associated with the expression of γ- and α7-nAChR in the skeletal muscle. Ulinastatin can improve this effect by inhibiting the expression of these receptors.

Resting-state functional MRI of abnormal baseline brain activity in young depressed patients with and without suicidal behavior

BACKGROUND Suicide among youth is a major public health challenge, attracting increasing attention. However, the neurobiological mechanisms and the pathophysiology underlying suicidal behavior in depressed youths are still unclear. The fMRI enables a better understanding of functional changes in the brains of young suicide attempters with depressive disorder through detecting spontaneous neural activity. The purpose of this study was to identify the relationship between abnormalities involving local brain function and suicidal attempts in depressed youths using resting-state fMRI (RS-fMRI). METHOD Thirty-five depressed youths aged between 15 and 29 years with a history of suicidal attempts (SU group), 18 patients without suicidal attempts (NSU group) and 47 gender-, age- and education-matched healthy controls (HC) underwent psychological assessment and R-fMRI. The differences in fractional amplitude of low-frequency fluctuation (ALFF) among the three groups were compared. The clinical factors correlated with z-score ALFF in the regions displaying significant group differences were investigated. The ROC method was used to evaluate these clusters as markers to screen patients with suicidal behavior. RESULTS Compared with the NSU and HC groups, the SU group showed increased zALFF in the right superior temporal gyrus (r-STG), left middle temporal gyrus (L-MTG) and left middle occipital gyrus (L-MOG). Additionally, significantly decreased zALFF values in the L-SFG and L-MFG were found in the SU group compared with the NSU group, which were negatively correlated with BIS scores in the SU group. Further ROC analysis revealed that the mean zALFF values in these two regions (sensitivity=83.3% and specificity=71.4%) served as markers to differentiate the two patient subtypes. CONCLUSION The SU group had abnormal spontaneous neural activity during the resting state, and decreased activity in L-SFG and L-MFG was associated with increased impulsivity in SU group. Our results suggested that abnormal neural activity in these brain regions may represent a potential neurobiological diathesis or predisposition to suicidal behavior in youth depression.

Sepsis induced denervation-like changes at the neuromuscular junction.

BACKGROUND The aim of this study was to determine the functional and biochemical changes at the neuromuscular junction (NMJ) induced by sepsis. MATERIALS AND METHODS Male Sprague-Dawley rats were divided into three groups as follows: control, denervation, and sepsis. The rats were subjected to cecal ligation and puncture (CLP) or tibias nerve transection. NMJ function and the area of end plates were assessed, and the protein level of acetylcholine receptors and axonal neuregulin-1 was evaluated on postoperative days 1, 7, and 14. RESULTS In the control group, the amplitude of compound muscle action potential (CMAP) was 16.51 ± 2.53 mV. In the sepsis group, the amplitude of CMAP decreased, and duration was prolonged on postoperative days 7 and 14 (P < 0.01). Meanwhile, motor conduction velocity decreased significantly (P < 0.01). CMAP was lost in the denervation group. The twitch tension magnitude gradually declined (P < 0.05) in the sepsis group, although it could not be recorded after lesion. Sepsis and denervation upregulated the expression of γ-nicotinic acetylcholine receptor (nAChR) and α7-nAChR in muscle membrane, compared with those in normal NMJ (261.4 ± 26.5 μm(2)). The NMJ area decreased from 254.6 ± 23.8 μm(2) (1 d after CLP) to 275.4 ± 22.6 μm(2) (7 d after CLP) to 322.7 ± 34.4 μm(2) (14 d after CLP). The postsynaptic NMJ had more discrete fragments (3.84 ± 0.6) compared with the control group (2.13 ± 0.4; P < 0.01). After denervation, NMJ underwent fragmentation and the number of discrete fragments increased (5.57 ± 1.2; P < 0.01). NMJ area increased from 254.6 ± 23.8 μm(2) (1 d after CLP) to 275.4 ± 22.6 μm(2) (7 d after CLP) to 322.7 ± 34.4 μm(2) (14 d after CLP). Sepsis induced neuregulin-1 to decrease from 1 d up to 2 wk compared with the control group (P < 0.05). CONCLUSIONS Chronic sepsis has a denervation-like effect on the NMJ, which was indicated by upregulation of heterogeneous nAChRs, the increased area of end plates, and demyelination of the motoneuron axon.

Behavioral and molecular responses to electroconvulsive shock differ between genetic and environmental rat models of depression

Depression׳s causes play a role in individuals׳ different responses to antidepressant treatments, which require advancements. We investigated the mechanisms behind and responses to a highly effective antidepressant treatment, electroconvulsive therapy (ECT), in rat models with different (genetic or environmental) depression causes. Wistar Kyoto (WKY) rats and Wistar rats treated with chronic unpredictable mild stresses (CUMS) were used as genetic and environmental rat models of depression, respectively. The rats underwent electroconvulsive shock (ECS, the animal analog of ECT) or sham ECS. We performed a sucrose preference test, open field test, and Morris water maze to assess behavior. Hippocampal neuron numbers were measured with Nissl stain. Hippocampal BDNF, CREB, and p-CREB proteins were assayed with ELISA or western blotting. The main results showed that ECS impaired WKY rats׳ memories but improved CUMS rats׳ memories. It elevated hippocampal BDNF and CREB proteins only in CUMS rats, while it improved depressive behavior and hippocampal p-CREB protein levels in both rats, with more effective regulations in the CUMS rats. ECS did not change the hippocampal neuron number in both rats. These findings suggest that ECS exerted up-regulating effects on hippocampal BDNF and CREB (and its phosphorylation) in depressed rats, and the environmental model responded better.

Correlation of suicidal ideation with social support and quality of life among college students

Objective To investigate the correlation of suicidal ideation with social support and quality of life(QOL) among college students.Methods A total of 9 808college students in Chongqing were surveyed by using stratified cluster random sampling method to investigate their suicidal ideation status;the association of suicidal ideation with social support and QOL was analyzed by multipleregression correlation analysis.Results The reporting rate of suicidal ideation was 13.04%in our survey,especially high in females(16.39%),art students(15.09%),students with religious belief(15.05%),and students with history of suicide attempt(68.64%).The students with suicidal ideation had lower scores in social support, objective support,subjective support,utilization of support,QOL,physical condition,psychological health,economic status, working condition,family relationship and interpersonal relationship with others than students without suicidal ideation(P 0.01).It was also found that the suicidal ideation was negatively correlated with subjective support(r=-0.100,P0.01), utilization of support(r=-0.094,P0.01),physical condition(r=-0.127,P0.01),psychological health(r=-0.067, P0.01),and economic status(r=-0.081,P0.01).Conclusion College students in Chongqing have a high prevalence ofsuicidal ideation.Society,family and school should attach more importance to the mental health status of college students and improvement of social support system for college students;comprehensive measures should be taken to prevent suicidal ideation and behavior.