Xuelian Wang

Preliminary findings in ablating the nucleus accumbens using stereotactic surgery for alleviating psychological dependence on alcohol.

We studied the effect of stereotactic surgery in cases of alcohol dependence. Twelve patients with a psychological dependence on alcohol (treated systematically with medication for detoxification 3-8 times in various rehabilitation centers before, but had relapsed within 2 weeks after withdrawal) were treated by ablating the nucleus accumbens (NA(C)) bilaterally using stereotactic surgery. The therapeutic effect and safety evaluation index of the surgery were analyzed. The timing of the conducted evaluations was preoperatively and in the sixth postoperative month. Currently, relapse has not occurred in 9 cases. Relapse occurred in 3 cases after surgery. The prevalence of relapse was 16.7% within 6 months, and 25% within 12 months. Non-specific complications of this type of surgery (e.g., intracranial hematoma, infection) were not observed. One case in 12 patients suffered dysosmia, but he recovered completely 4 months later after surgery. The full-scale intelligence quotient (FSIQ) and memory quotient (MQ) of these patients were significantly improved 6 months postoperatively compared with preoperatively. The severity of alcohol dependence scale and a scale measuring alcohol craving in these patients were significantly decreased. There were also significant changes over time in the Minnesota multiphasic personality inventory (MMPI) profile, suggesting a decrease in depression, irritability, and psychopathy. Ablating specified targets (NA(C)) using stereotactic surgery is a safe method to alleviate alcohol craving, reduce relapse rates and improve quality-of-life in patients with psychological dependence on alcohol.

Correlation of microRNA-375 downregulation with unfavorable clinical outcome of patients with glioma

BACKGROUND AND AIM MicroRNA-375 (miR-375) is frequently demonstrated to be frequently dysregulated and functions as a tumor suppressor or an oncogene in different cancer types. However, its roles in human gliomas have not been reported. The aim of this study was to investigate the expression pattern and clinical significance of miR-375 in patients with gliomas. METHODS Real-time quantitative RT-PCR assay was performed to detect miR-375 expression in human gliomas and non-neoplastic brain tissues. Then, the association of miR-375 expression with clinicopathological factors and prognosis of glioma patients was also statistically analyzed. RESULTS miR-375 expression was significantly decreased on average in glioma tissues relative to non-neoplastic brain tissues (P<0.0001) with ascending pathological grade. Then, the low miR-375 expression in glioma tissues was significantly associated with advanced pathological grade (P=0.003) and low Karnofsky performance score (KPS, P=0.01). Moreover, both univariate and multivariate Cox regression analyses determined that loss of miR-375 expression effectively predicted the decreased overall survival in patients with gliomas. CONCLUSIONS These findings offer the first convinced evidence that the downregulation of miR-375 expression in human gliomas may play an inhibitory role during the tumor development. This miRNA might function as a candidate unfavorable prognostic marker for human gliomas.

Gypenosides protects dopaminergic neurons in primary culture against MPP+-induced oxidative injury

Oxidative injury has been implicated in the etiology of Parkinsons disease (PD). Gypenosides (GPs), the saponins extract derived from the Gynostemma pentaphyllum, has various bioactivities. In this study, GPs was investigated for its neuroprotective effects on the 1-methyl-4-phenylpyridinium ion (MPP(+))-induced oxidative injury of dopaminergic neurons in primary nigral culture. It was found that GPs pretreatment, cotreatment or posttreatment significantly and dose-dependently attenuated MPP(+)-induced oxidative damage, reduction of dopamine uptake, loss of tyrosine hydrolase (TH)-immunopositive neurons and degeneration of TH-immunopositive neurites. However, the preventive effect of GPs was more potential than its therapeutical effect. Most importantly, the neuroprotective effect of GPs may be attributed to GPs-induced strengthened antioxidation as manifested by significantly increased glutathione content and enhanced activity of glutathione peroxidase, catalyze and superoxide dismutase in nigral culture. The neuroprotective effects of GPs are specific for dopaminergic neurons and it may have therapeutic potential in the treatment of PD.

Exosomes of BV-2 cells induced by alpha-synuclein: Important mediator of neurodegeneration in PD

Parkinsons disease (PD) is a progressive neurodegenerative disease. Alpha-synuclein aggregation, which can activate microglia to enhance its dopaminergic neurotoxicity, plays a central role in the progression of PD. However the mechanism is still unclear. To investigate how alpha-synuclein affects the neuron, exosomes were derived from alpha-synuclein treated mouse microglia cell line BV-2 cells by differential centrifugation and ultracentrifugation. We found that alpha-synuclein can induce an increase of exosomal secretion by microglia. These activated exosomes expressed a high level of MHC class II molecules and membrane TNF-α. In addition, the activated exosomes cause increased apoptosis. Exosomes secreted from activated microglias might be important mediator of alpha-synuclein-induced neurodegeneration in PD.

Activity of p44/42 MAP kinase in the caudal subnucleus of trigeminal spinal nucleus is increased following perioral noxious stimulation in the mouse

The extracellular signal-regulated protein kinase-1 and -2 (ERK1 and ERK2), also referred to as the p44/42 mitogen-activated protein kinase (p44/42 MAP kinase), plays an essential role in neuronal signal transduction, but its function involved in nociceptive response has not been deeply studied yet. Here we report immunohistochemical evidence that p44/42 MAPK might be critical in nociceptive response. We found that after formalin was injected into the perioral skin of the upper lip of mice, the number of activated p44/42 MAPK-like immunoreactive neurons was significantly increased in the laminae I and II of the caudal subnucleus of the trigeminal spinal nucleus (Sp5C). The positive neurons and fibers were mostly concentrated in the middle portion of Sp5C dorsoventrally, where the afferent fibers innervating the skin of the upper lip are terminated. The reactive products were localized in perikarya, dendrites, nuclei, and diffusely in the neuropil. The present result suggests that p44/42 MAPK may be important in the transmission and modulation of noxious information in Sp5C.

Long-term effects of bilateral deep brain stimulation of the subthalamic nucleus on depression in patients with Parkinson's disease

OBJECTIVE To study the long-term effects of deep brain stimulation (DBS) of the bilateral subthalamic nucleus (STN) on depression in patients with Parkinsons disease (PD) and to discuss the mechanism. METHODS A STN-DBS group (n = 27) and anti-Parkinsons medication control group with paired designing were set up. The evaluation of the depression and motor function was performed a total of six times. Depression was evaluated by the Self-Rating Depression Scale (SDS) and Hamilton Rating Scale for Depression (HAMD). Motor function was evaluated by the third part of the Unified Parkinsons Disease Rating Scale (UPDRS-III). RESULTS Compared with the preoperative and the medication control group, the UPDRS-III scores of the STN-DBS group decreased remarkably within 18 months postoperatively (P < or = 0.001), and the SDS scores decreased notably within 6 months postoperatively (P < or = 0.05), and the HAMD scores decreased notably within 3 months postoperatively (P < or = 0.05). The UPDRS-III scores were strongly correlated with their SDS scores within 6 months postoperatively (P < or = 0.05), especially at 5 weeks postoperation (P < or = 0.001). UPDRS-III scores were also strongly correlated with HAMD scores at 5 weeks postoperation (P < or = 0.05). The mean value of the bilateral voltages was obviously correlated with SDS and HAMD scores (P < or = 0.05) within 18 months postoperatively. CONCLUSION The improvement in motor symptoms resulting from STN-DBS can improve depression in PD patients, but its long-term effects were unremarkable. Within the treatment range, the higher the mean value of bilateral voltages then the more severe was the depression in PD patients.

Hyperphosphorylation of tau protein by calpain regulation in retina of Alzheimer's disease transgenic mouse

Aim to investigate phosphorylated tau expression and its pathogenic mechanism in eye of Alzheimers disease (AD) transgenic mice. Levels of tau, phosphorylated tau and other related factors (p35/p25, Cyclin-dependent kinase 5 (Cdk5), calpain) were observed by western blot. β-Amyloid (Aβ) plaques and neuron-fibrillary tangles (NFTs) in APP/PS1 double transgenic mice were detected by immuno-histochemistry. We found that hyper-expression of phosphorylated tau was detected in retina, and only a few or no expressed in optic nerve, cornea and lens of transgenic mice. Increased senile plaques (Aβ) and NFTs were observed in transgenic mice accompanying with increased tau phosphorylation. The increased tau phosphorylation was associated with a significant increase in production of p35 and p25, and up-regulation of calpain. In conclusion, phosphorylated tau level was highly expressed in retina of AD transgenic mice. The pathogenic mechanism of AD was triggered by accelerating tau pathology via calpain-mediated tau hyper-phosphorylation in retina of an AD mice model.

Dopamine depletion increases the power and coherence of high-voltage spindles in the globus pallidus and motor cortex of freely moving rats☆

Studies on patients with Parkinsons disease and in animal models have observed enhanced synchronization of oscillations in several frequency bands within and between the cortical-basal ganglia (BG) structures. Recent research has also shown that synchronization of high-voltage spindles (HVSs) in the cortex, striatum and substantia nigra pars reticulate is increased by dopamine depletion. However, more evidence is needed to determine whether HVS activity in the whole cortex-BG network represents homologous alteration following dopamine depletion. As the globus pallidus (GP) is in a central position to propagate and synchronize oscillations in the cortical-BG circuits, we employed local-field potentials and electrocorticogram to simultaneously record oscillations in the GP and primary (M1) and secondary (M2) motor cortices on freely moving 6-hydroxydopamine (6-OHDA) lesioned and control rats. Results showed that HVS episodes recorded from GP, and M2 and M1 cortex areas were more numerous and longer in 6-OHDA lesioned rats compared to controls. Relative power associated with HVS activity in the GP, and M2 and M1 cortices of 6-OHDA lesioned rats was significantly greater than that for control rats. Coherence values for HVS activity between the GP, and M2 and M1 cortex areas were significantly increased by dopamine depletion. Time lag between the M1 cortex HVS and GP HVS was significantly shorter for dopamine depleted than normal rats. Findings indicate a crucial rule for dopamine in the regulation of HVS activity in the whole cortical-BG circuit, and suggest a close relationship between abnormally synchronized HVS oscillations in the cortex-BG network and Parkinsons disease.

Associations between bilateral subthalamic nucleus deep brain stimulation (STN-DBS) and anxiety in Parkinson's disease patients: a controlled study.

The authors explored the associations between subthalamic nucleus deep brain stimulation (STN-DBS) and anxiety in Parkinsons disease (PD) patients. Recent research suggests that anxiety may be one of the earliest manifestations of PD; however, the lack of a dopamine-medication control group is a major limitation of these studies. Authors paired a group of 31 bilateral STN-DBS PD patients (STN-DBS group) with 31 dopamine-medicated PD patients (Medication-control group) and used various psychological assessment scales for group evaluations. These were completed 1 month preoperatively, and 3 weeks, 5 weeks, 2 months, 4 months, 7 months, and 13 months postoperatively. As compared with the Medication group, the STN-DBS group improved in motor functioning and general status after 1 week Stimulator Power-On; State-Anxiety improved significantly at 1 week and 1 month after Stimulator Power-On, but was not significant at the subsequent time-points. Anxiety scores remained stable before 3rd-month Stimulator Power-On, but got worse after that time. In the STN-DBS group, S-AI was positively related to motor symptoms and life quality preoperatively and 4 months postoperatively, but, in the Medication group, this correlation existed throughout the study. PD-related anxiety decreased in STN-DBS patients because of the improvement in motor function for a short time; however, as the voltages and pulse-widths grew higher with time, the PD-related anxiety became worse.

Long-Term Changes in the Personality and Psychopathological Profile of Opiate Addicts after Nucleus Accumbens Ablative Surgery Are Associated with Treatment Outcome

Objective: To investigate the long-term outcome and changes of the personality and psychopathological profile of opiate addicts after bilateral stereotactic nucleus accumbens (NAc) ablative surgery. Methods: 60 patients were followed up for 5 years and abstinent status and adverse events were evaluated. NAc lesion volumes and locations were obtained by postoperative MRI scans. The Chinese version of the Eysenck Personality Questionnaire (EPQ-RSC), the Symptom Checklist-90-Revised (SCL-90-R), the Beck Depression Inventory (BDI), the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the World Health Organization’s Quality of Life Questionnaire – Brief Version (WHOQOL-BREF) were administered to the patients before and 5 years after the stereotactic surgery. Results: The total abstinence rate of all patients in their 5th postoperative year was 47.4%. The abstinent patients had a significantly larger lesion volume than the relapsed ones, but a larger lesion volume also increased the risk of adverse events. 5 years after surgery, the abstinent patients showed significant decreases on the Psychoticism (EPQ-P) and Neuroticism (EPQ-N) scores by EPQ-RSC, a significant decline on the Global Severity Index and the subscores in all 10 dimensions by SCL-90-R, significant decreases on the BDI and Y-BOCS scores, and significant improvements on the scores of all domains by WHOQOL-BREF, while for the relapsed patients, only the subscores of obsessive-compulsive by SCL-90-R and the Y-BOCS scores significantly decreased. Postoperative analysis revealed that the abstinent patients had a significantly better score than the relapsed ones by various instruments, and NAc lesion volumes and locations did not correlate with the outcome of any of these instruments. Conclusion: The bilateral ablation of NAc by stereotactic neurosurgery was a feasible method for alleviating psychological dependence on opiate drugs and preventing a relapse. Long-term follow-up suggested that surgery can improve the personality and psychopathological profile of opiate addicts with a trend towards normal levels, provided persistent abstinence can be maintained; relapse, on the other hand, may ruin this effect.