Follow-up study on ThinPrep cytology test-positive patients in tropical regions.

BACKGROUND: As shown in the statistics from the World Health Organization, it is estimated that approximately 75000 new cases of cervical cancer occur every year in China. In 2008, 33000 people died of cervical cancer in China. It is proven that most women are at risk of cervical cancer. The progression from human papillomavirus (HPV) infection to cervical cancer can be several years or decades, which offers a unique opportunity to prevent cancer. AIM: To observe the changes in ThinPrep cytology tests (TCT) and HPV infection in patients who were detected to be positive via TCT screening of cervical cancer and further explore the biopsy results. METHODS: This paper performed a follow-up study on 206 cervical cancer screening-positive patients of 12231 total cases from our previous research. We conducted an observational study on the TCT results based on the interpretation of The Bethesda System. RESULTS: Over a 5-year period, 10 cases received consistent follow-up. The proportions of cases in which glandular epithelial lesions were detected increased over the follow-up period. The differences between the years were statistically significant (P < 0.01). Over the 5 years, the proportion of patients whose squamous epithelial lesions transformed into glandular epithelial lesions increased yearly. Annual positive rates of HPV infection were: year 1, 73% (24/33); year 2, 43% (6/14); year 3, 36% (9/25); year 4, 50% (9/18); and year 5, 25% (6/24). The positive detection rate after biopsy over a 9-year period was 29%. CONCLUSION: The follow-up study for 5 years to 9 years revealed a tendency to change from squamous epithelial lesions to glandular epithelial lesions and an improvement of the disease (which had not been reported previously). The HPV test indicated a high negative conversion ratio of the viral infection. However, the follow-up cases were not found to have persistent infection of high-risk HPV. Therefore, early intervention of cervical cancer screening is necessary. Low re-examination compliance, patient education, and preventive measures should be enhanced.

Show, Match and Segment: Joint Weakly Supervised Learning of Semantic Matching and Object Co-Segmentation.

We present an approach for jointly matching and segmenting object instances of the same category within a collection of images. In contrast to existing algorithms that tackle the tasks of semantic matching and object co-segmentation in isolation, our method exploits the complementary nature of the two tasks. The key insights of our method are two-fold. First, the estimated dense correspondence fields from semantic matching provide supervision for object co-segmentation by enforcing consistency between the predicted masks from a pair of images. Second, the predicted object masks from object co-segmentation in turn allow us to reduce the adverse effects due to background clutters for improving semantic matching. Our model is end-to-end trainable and does not require supervision from manually annotated correspondences and object masks. We validate the efficacy of our approach on five benchmark datasets: TSS, Internet, PF-PASCAL, PF-WILLOW, and SPair-71k, and show that our algorithm performs favorably against the state-of-the-art methods on both semantic matching and object co-segmentation tasks.

Six families with balanced chromosome translocation associated with reproductive risks in Hainan Province: Case reports and review of the literature.

BACKGROUND: Balanced translocation refers to the process where breakage and reconnection of chromosomes occur at abnormal positions. As the genetic substance with balanced translocation in individuals does not change, which is usually characterized by normal phenotype and intelligence, the individuals seek medical service after many miscarriages, resulting in considerable mental and physical burdens of the family members. In the current era with rapid advances in detection technology, cytogenetic examination, as a definitive approach, still plays an essential role. CASE SUMMARY: We report six cases with balanced chromosome translocation: Case 1: 46,XY,t(3;12)(q27;q24.1), infertility after 3 years of marriage; Case 2: 46,XX,t(4;16)(q31;q12), small uterus and irregular menstruation; Case 3: 46,XY,t(4;5)(q33;q13),9qh+, not pregnant after arrested fetal development; Case 4: 46,XX,t(11;17)(q13;p11.2), not pregnant after two times of spontaneous abortion; Case 5: 46,XX,t(10;13)(q24;q21.2), not pregnant after arrested fetal development for once; Case 6: 46,XX,t(1;4)(p36.1;q31.1), not pregnant after arrested fetal development for two times. The first four cases had chromosomal aberration karyotypes. CONCLUSION: These results suggested that balanced chromosomal translocation carriers are associated with reproductive risks and a very high probability of abnormal pregnancy. The discovery of the first four reported chromosomal aberration karyotypes provides an important basis for studying the occurrence of genetic diseases.

Risperidone ameliorates cognitive deficits, promotes hippocampal proliferation, and enhances Notch signaling in a murine model of schizophrenia.

Antipsychotic agents have been reported to promote hippocampal neurogenesis and improve cognitive deficits; yet, the molecular mechanisms underlying these actions remain unclear. In the present study, we used a murine model of schizophrenia induced by 5-day intraperitoneal injection with the non-competitive N-methyl-d-aspartate receptor antagonist MK801 (0.3mg/kg/day) to assess cognitive behavioral deficits, changes in Notch signaling, and cellular proliferation in the hippocampus of adult male C57BL/6 mice after 2-week administration of risperidone (Rip, 0.2mg/kg/day) or vehicle. We then utilized in vivo stereotaxic injections of a lentivirus expressing a short hairpin RNA (shRNA) for Notch1 into the dentate gyrus to examine the role of Notch1 in the observed actions of Rip. We found that Rip ameliorated cognitive deficits and restored cell proliferation in MK801-treated mice in a manner associated with the up-regulation of Notch signaling molecules, including Notch1, Hes1, and Hes5. Moreover, these effects were abolished by pretreatment with Notch1 shRNA. Our results suggest that the ability of Rip to improve cognitive function in schizophrenia is mediated in part by Notch signaling.

Isoflurane exposure regulates the cell viability and BDNF expression of astrocytes via upregulation of TREK­1.

Neonatal isoflurane exposure in rodents disrupts hippocampal cognitive functions, including learning and memory, and astrocytes may have an important role in this process. However, the molecular mechanisms underlying this disruption are not fully understood. The present study investigated the role of TWIK­related K+ channel (TREK­1) in isoflurane­induced cognitive impairment. Lentiviruses were used to overexpress or knockdown TREK­1 in astrocytes exposed to increasing concentrations of isoflurane or O2 for 2 h. Subsequently, the mRNA and protein expression of brain­derived neurotrophic factor (BDNF), caspase­3, Bcl­2­associated X (Bax) and TREK­1 was measured by reverse transcription­ quantitative polymerase chain reaction and western blot analysis, respectively. In addition, cell viability was assessed by a 2­(4­Iodophenyl)­3­(4­nitrophenyl)­5­(2,4­disulfophenyl)­ 2H­tetrazolium monosodium salt assay. The results demonstrated that, prior to manipulating TREK­1, isoflurane significantly decreased the cell viability and BDNF expression, and increased Bax, caspase­3 and TREK­1 expression was observed. However, TREK­1 overexpression in astrocytes significantly downregulated BDNF expression, and upregulated Bax and caspase­3 expression. Furthermore, lentiviral­mediated short hairpin RNA knockdown of TREK­1 effectively inhibited the isoflurane­induced changes in BDNF, Bax and caspase­3 expression. Taken together, the results of the present study indicate that isoflurane­induced cell damage in astrocytes may be associated with TREK­1­mediated inhibition of BDNF and provide a reference for the safe use of isoflurane anesthesia in infants and children.

Disturbed Brain Activity in Resting-State Networks of Patients with First-Episode Schizophrenia with Auditory Verbal Hallucinations: A Cross-sectional Functional MR Imaging Study.

Purpose To investigate auditory verbal hallucination (AVH)-specific patterns of brain activity within the resting-state networks (RSNs) that have been proposed to underpin the neural mechanisms of schizophrenia (SZ). Materials and Methods This cross-sectional study was approved by the local ethics committee, and written informed consent was obtained from all participants prospectively recruited. Independent component analysis was used to investigate RSNs in 17 patients with first-episode untreated SZ with AVHs, 15 patients with SZ without AVHs, and 19 healthy control subjects who underwent resting-state functional magnetic resonance imaging. Dual regression was implemented to perform between-group analysis. Regional brain function was then explored within RSNs by using the amplitude of low-frequency fluctuation. Two-sample t tests were used to compare regional brain function between the two patient groups, and Pearson correlation analysis was used to characterize the relationship between imaging findings and severity of AVHs. Receiver operating characteristic analysis was used to evaluate the diagnostic performance of these brain function measures. Results Independent component analysis demonstrated symptom-specific abnormal disrupted coactivation within the auditory, default mode, executive, motor, and frontoparietal networks and was pronounced in the auditory cortex, supramarginal gyrus, insula, putamen, dorsolateral prefrontal cortex, angular gyrus, precuneus, and thalamus (P < .05 with false discovery rate correction). Amplitude of low-frequency fluctuation analysis demonstrated similar patterns within these RSNs (P < .05 with false discovery rate correction). Furthermore, a positive correlation between the degree of coactivation within the motor network and the severity of AVHs was observed in patients with SZ with AVHs (r = 0.67, P = .003). The area under the receiver operating characteristic curve was 0.76-0.90 for all RSNs. Conclusion These findings indicate that dysfunctional brain regions are involved in auditory processing, language production and monitoring, and sensory information filtering in patients with SZ with AVHs, which may be helpful in furthering the understanding of pathophysiological correlates of AVHs in SZ. Online supplemental material is available for this article.

An assessor-blinded, randomized comparison of efficacy and tolerability of switching from olanzapine to ziprasidone and the combination of both in schizophrenia spectrum disorders.

BACKGROUND: Ziprasidone (ZIP) is often used with olanzapine (OLZ) in 'switch' and combination therapy but empirical evidence to support these strategies is limited. OBJECTIVE: This study was therefore designed to compare the efficacy and tolerability of switching from OLZ to ZIP, the combination of both medications, and OLZ and ZIP monotherapy, in patients with schizophrenia spectrum disorders (SSD). METHODS: In this 12 week open-label, assessor-blinded randomized trial, 148 patients with SSD who had not used antipsychotics for at least 3 months were assigned to ZIP (n = 49) or OLZ monotherapy (n = 31); OLZ for 4 weeks then a switch to ZIP (OLZ/ZIP, n = 35); or combination therapy (OLZ + ZIP, n = 33). The severity of psychosis and abnormal involuntary movements was evaluated at baseline, 1, 2, 4, 8, and 12 weeks using standard instruments. Baseline-to-endpoint changes in weight gain and metabolic measures were compared. RESULTS: The efficacy of both OLZ/ZIP and OLZ + ZIP was comparable OLZ monotherapy and better than ZIP monotherapy in reducing overall psychotic and negative symptoms at most 8 and 12 week measurement points. Changes in weight gain, glucose, and lipid measures did not differ between OLZ/ZIP and OLZ + ZIP, but were markedly higher following OLZ monotherapy. The OLZ + ZIP group had the lowest overall incidence of adverse events and extrapyramidal symptoms of all the treatment regimens. CONCLUSIONS: We conclude that combining ZIP and OLZ at the outset of treatment is superior to switching from OLZ to ZIP in terms of improving psychotic symptoms and limiting movement side effects without increasing the risk of metabolic syndrome.

Quetiapine Ameliorates Schizophrenia-Like Behaviors and Protects Myelin Integrity in Cuprizone Intoxicated Mice: The Involvement of Notch Signaling Pathway.

BACKGROUND: White matter disturbances and myelin impairment are key features of schizophrenia. The antipsychotic drug quetiapine can promote the maturation of oligodendrocytes, but the molecular mechanisms remain largely unknown. METHODS: The schizophrenia-like behaviors, degrees of demyelination, and levels of Notch signaling molecules in forebrains of adult male C57BL/6 mice were examined after fed with cuprizone (0.2% wt/wt) in the presence or absence of 10mg/kg/d quetiapine for 6 weeks. These parameters were also observed after the transcranial injection of Notch signaling inhibitor MW167 (1mM) daily during the last week of the treatment period. RESULTS: Quetiapine ameliorated the schizophrenia-like behaviors and decreased expression of myelin basic protein and inhibition of Notch signaling molecules, such as Notch1, Hes1, and Hes5, in the forebrain that induced by cuprizone. These beneficial effects of quetiapine were abolished by MW167. CONCLUSIONS: The antipsychotic and myelin protective effects of quetiapine are mediated by Notch signaling in a mouse model of cuprizone-induced demyelination associated with schizophrenia-like behaviors. The Notch pathway might therefore be a novel target for the development of antipsychotic drugs.

Quetiapine and repetitive transcranial magnetic stimulation ameliorate depression-like behaviors and up-regulate the proliferation of hippocampal-derived neural stem cells in a rat model of depression: The involvement of the BDNF/ERK signal pathway.

Quetiapine (QUE) and repetitive transcranial magnetic stimulation (rTMS) have been considered to be possible monotherapies for depression or adjunctive therapies for the treatment of the resistant depression, but the underlying mechanisms remain unclear. The present study aimed to assess the effects of combined QUE and rTMS treatment on depressive-like behaviors, hippocampal proliferation, and the in vivo and in vitro expressions of phosphorylated extracellular signal-regulated protein kinase (pERK1/2) and brain-derived neurotrophic factor (BDNF) in male Sprague-Dawley rats. The administration of QUE and rTMS was determined not only to reverse the depressive-like behaviors of rats exposed to chronic unpredictable stress (CUS) but also to restore the protein expressions of pERK1/2 and BDNF and cell proliferation in the hippocampus. Additionally, QUE and rTMS promoted the proliferation and increased the expression of pERK1/2 and BDNF in hippocampal-derived neural stem cells (NSCs), and these effects were abolished by U0126. Taken together, these results suggest that the antidepressive-like effects of QUE and rTMS might be related to the activation of the BDNF/ERK signaling pathway and the up-regulation of cell proliferation in the hippocampus.

Repetitive transcranial magnetic stimulation ameliorates anxiety-like behavior and impaired sensorimotor gating in a rat model of post-traumatic stress disorder.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been employed for decades as a non-pharmacologic treatment for post-traumatic stress disorder (PTSD). Although a link has been suggested between PTSD and impaired sensorimotor gating (SG), studies assessing the effects of rTMS against PTSD or PTSD with impaired SG are scarce. AIM: To assess the benefit of rTMS in a rat model of PTSD. METHODS: Using a modified single prolonged stress (SPS&S) rat model of PTSD, behavioral parameters were acquired using open field test (OFT), elevated plus maze test (EPMT), and prepulse inhibition trial (PPI), with or without 7 days of high frequency (10Hz) rTMS treatment of SPS&S rats. RESULTS: Anxiety-like behavior, impaired SG and increased plasma level of cortisol were observed in SPS&S animals after stress for a prolonged time. Interestingly, rTMS administered immediately after stress prevented those impairment. CONCLUSION: Stress-induced anxiety-like behavior, increased plasma level of cortisol and impaired PPI occur after stress and high-frequency rTMS has the potential to ameliorate this behavior, suggesting that high frequency rTMS should be further evaluated for its use as a method for preventing PTSD.

Anti-depressive mechanism of repetitive transcranial magnetic stimulation in rat: the role of the endocannabinoid system.

Repetitive transcranial magnetic stimulation (rTMS) to treat depression has been thoroughly investigated in recent years. However, the underlying mechanisms are not fully understood. In this study, a chronic unpredictable mild stress (CUMS) paradigm was applied to male Sprague Dawley rats. Then rTMS was performed for 7 consecutive days, and the anti-depressive effects were evaluated by the sucrose preference test (SPT), the forced swimming test (FST), and the open-field test (OFT). Hippocampal cannabinoid type I receptor (CB1) expression was measured, and the expression levels of brain-derived neurotrophic factor (BDNF), Bcl-2, and Bax and the number of bromodeoxyuridine (BrdU)-positive cells were also investigated. These parameters were also observed after the selective CB1 receptor antagonist AM251 was used as a blocking agent. The results showed that CUMS induced a significant decrease in sucrose preference, a significant increase in immobility time in the FST, and a significantly decreased horizontal distance in the OFT. In addition, reduced hippocampal CB1 receptor, BDNF, and Bcl-2/Bax protein expression levels in CUMS rats, as well as decreased cell proliferation were also observed in the dentate gyrus. Meanwhile, rTMS treatment up-regulated cell proliferation; elevated CB1 receptor, BDNF, and Bcl-2/Bax expression levels in the hippocampus; and ameliorated depressive-like behaviors. All of these beneficial effects were abolished by AM251. These results indicate that rTMS increases BDNF production and hippocampal cell proliferation to protect against CUMS-induced changes through its effect on CB1 receptors.

Quetiapine add-on therapy improves the depressive behaviors and hippocampal neurogenesis in fluoxetine treatment resistant depressive rats.

Quetiapine, an atypical antipsychotic, may have efficacy as augmentation therapy in treatment resistant depression (TRD), but evidence is limited and the underlying mechanism remains poorly understood. Therefore, this study was aimed to investigate whether and how quetiapine can be served as an augmentation agent in fluoxetine treatment resistant depressive rats induced by chronic unpredictable mild stress (CUMS). In this study, the effects of CUMS regimen and antidepressant treatment were assessed by behavioral tests and hippocampal neurogenesis. Approximately 20-30% of depressive rats respond poorly to fluoxetine treatment. In their hippocampus, a significant decrease of neurogenesis was also observed. However, quetiapine add-on therapy significantly improved the depressive behaviors and increased the number of the newborn neurons in the hippocampus of fluoxetine treatment resistant depressive rats. Thus, our results suggest that quetiapine may be used as an augmentation agent in the treatment resistant depression partly mediated by increasing the number of newborn neurons in the hippocampus.

Paroxetine up-regulates neurogenesis in hippocampus-derived neural stem cell from fetal rats.

Paroxetine is a widely used antidepressant in clinic. Besides its role in inhibition of serotonin reuptake, resent studies indicate that the increase of hippocampal neurogenesis is also involved in its pharmacology. However, only limited data are available in this regard and its effect on the hippocampus-derived neural stem cell (NSCs) has not been well elucidated. In present study, we utilized hippocampus-derived NSCs from fetal rats to investigate the direct effect of paroxetine on the neurogenesis of NSCs and explore the possible cellular and molecular mechanisms. The results showed that paroxetine not only promoted the proliferation of NSCs, but also promoted NSCs to differentiate into neurons other than glial cells. In addition, the elevated protein levels of phosphorylated ERK1/2, Bcl-2, and brain-derived neurotrophic factor were also observed after paroxetine was administered. Furthermore, the proliferative effect and promotion of NSCs differentiating predominantly into neurons of paroxetine was inhibited by U0126, an ERK1/2 phosphorylation inhibitor. In conclusion, these data indicate that paroxetine can promote neurogenesis of neural stem cells, and this effect might be mediated by ERK1/2 signal pathways.

Long-lasting effects of chronic rTMS to treat chronic rodent model of depression.

Repetitive transcranial magnetic stimulation (rTMS) has been demonstrated in the pre-clinical and clinical settings to have an antidepressant effect. However, studies on the long-lasting effect of rTMS, especially when the effect is measured after treatment has ceased for a few weeks is lacking. We examined this question in a chronic unpredicted mild stress (CUMS) rat model of depression. We gave 3 weeks of high frequency (15 Hz) rTMS, venlafaxine, or these two treatments combined to a modified CUMS paradigm, and then investigated the prolonged effect of treatments. Behavioral testing (sucrose preference test, open field test, forced swimming test, novelty suppressed feeding test), plasma hormone level, hippocampal BrdU labeling, and amount of related neurotropic factors were used to assess the effects of stress and treatments. Long-term chronic rTMS significantly reversed andehonic-like behavior, increased hippocampus cell proliferation, BDNF protein level, phosphorylation of ERK1/2 compared with CUMS rats two weeks after the cessation of rTMS treatment. However, the changes in plasma hormone level were not sustained for that amount of time. Venlafaxine had no interaction with the physical stimulation. Our results suggest that high frequency rTMS has long-lasting effects, which may have some relationship with neuroplasticity.

Electroconvulsive therapy improves antipsychotic and somnographic responses in adolescents with first-episode psychosis--a case-control study.

OBJECTIVE: Previous studies have demonstrated the effectiveness of electroconvulsive therapy (ECT) in pharmacotherapy-resistant neuropsychiatric conditions. This study aimed to evaluate the efficacy and safety of ECT in adolescents with first-episode psychosis. METHOD: This case-control study was conducted in inpatients aged 13-20 years with first-episode psychosis. Every three similar age and same gender patients consecutively recruited were randomly allocated to control and ECT group at a ratio of 1:2, while they had antipsychotic treatment. ECT treatment was performed for 3 sessions per week with a maximum of 14 sessions. The endpoint was discharge from hospital. Clinical outcomes were measured using hospital stay days, the Positive and Negative Syndrome Scale (PANSS) and response rate. Polysomnography (PSG) was conducted at baseline and at week 2. Safety and tolerability were also evaluated. RESULTS: Between March 2004 and November 2009, 112 eligible patients were allocated to control (n=38) and ECT (n=74) group. Additional ECT treatment significantly reduced hospital stay compared to controls (23.2±8.2 days versus 27.3±9.3 days, mean±SD, P=0.018). Survival analysis revealed that the ECT-treated group had a significantly higher cumulative response rate than controls (74.3% versus 50%, relative risk (RR)=1.961, P=0.001). Additional ECT also produced significantly greater improvement in sleep efficiency, rapid eye movement (REM) latency and density than control condition. The PSG improvement significantly correlated with reduction in scores on overall PANSS, positive symptoms, and general psychopathology. No patients discontinued ECT treatment regimen during hospital stay. The incidence of most adverse events was not different in the two groups, but ECT-treated group had more complaints of transient headache and dizziness than controls. CONCLUSIONS: ECT is an effective and safe intervention used in adolescents with first-episode psychosis. Its antipsychotic effects are associated with improved PSG variables. ECT can be considered as an early psychosis intervention.

Sertraline promotes hippocampus-derived neural stem cells differentiating into neurons but not glia and attenuates LPS-induced cellular damage.

Sertraline is one of the most commonly used antidepressants in clinic. Although it is well accepted that sertraline exerts its action through inhibition of the reuptake of serotonin at presynaptic site in the brain, its effect on the neural stem cells (NSCs) has not been well elucidated. In this study, we utilized NSCs separated from the hippocampus of fetal rat to investigate the effect of sertraline on the proliferation and differentiation of NSCs. The study demonstrated that sertraline had no effect on NSCs proliferation but it significantly promoted NSCs to differentiate into serotoninergic neurons other than glia cells. Furthermore, we found that sertraline protected NSCs against the lipopolysaccharide-induced cellular damage. These data indicate that sertraline can promote neurogenesis and protect the viability of neural stem cells.

Psychopathological, biological, and neuroimaging characterization of posttraumatic stress disorder in survivors of a severe coalmining disaster in China.

On July 29, 2007, a severe coalmine-flooded disaster occurred in central China and 69 miners were trapped in an about 1400 m underground coal pit. Fortunately, all of them were rescued after 75 h of the ordeal. At 3 and 6 months after the disaster, psychopathological profiles, plasma levels of cortisol and adrenocorticotropic hormone (ACTH) were evaluated in 48 survivors for posttraumatic stress disorder (PTSD) and comorbid symptoms. Magnetic resonance imaging (MRI) study was performed at 6 months. The prevalence of PTSD was 35.4% (17/48) at 3 months and 31.3% (15/48) at 6 months post-disaster, with high rates of comorbid symptoms. Risk factors for PTSD included previous traumatic experience, less than 5 years of being a miner, in an extremely exhausted or sick during the disaster, poor interpersonal relationship and poor sleep quality experienced before the disaster. Mean plasma cortisol levels at 6 months, but not at 3 months, were significantly higher in PTSD-positive subjects than the negative, and positively correlated with the severity of several comorbid symptoms. Either whole or regional brain volumes of PTSD-positive subjects were not significantly different from PTSD-negative subjects, but PTSD subjects had significantly reduced fractional anisotropy values in the right posterior cingulum and bilateral hippocampal body compared to subjects without PTSD. These results suggest that traumatic exposure in severe coalmining disasters results in considerable psychological consequences, with highly prevalent PTSD and comorbid symptoms, which are associated with previous traumatic experience, shorter-length underground services, and poor interpersonal relationships and sleep quality experienced before the disaster. Baseline cortisol level may be a useful biological predictor for different phases of the development of PTSD. The aberrant connectivity of the hippocampus and the cingulum may represent an early pathological response to trauma exposure.

Free and Easy Wanderer Plus (FEWP), a polyherbal preparation, ameliorates PTSD-like behavior and cognitive impairments in stressed rats.

Free and Easy Wanderer Plus (FEWP) is a well-known traditional Chinese medicine that has been shown to be effective in treating various mood disorders. The purpose of the present study was to determine whether FEWP could ameliorate stress-associated behavior in rats. Following the exposure to enhanced single prolonged stress (ESPS) paradigm, consisting of 2-hr constraint, 20-min forced swimming, ether-induced loss of consciousness, and an electric foot shock, animals were administered orally with FEWP (2.5, 5, or 10mg/kg daily) or vehicle for 2 weeks. Animals were then tested in the open field, elevated plus-maze, and Morris water maze. ESPS exposure resulted in pronounced anxiety-like behavior, without impairing locomotor activity, as indicated by significant decreases of time spent and number of entries into open arms in the elevated plus-maze test, and unaltered distance traveled in the open field test compared to unexposed animals. ESPS-exposed animals also displayed marked cognitive impairments, with significant increases of distance traveled and the escape latency to the underwater platform, and a striking decrease of time spent in the target quadrant with and without the removal of the platform in the water maze test. However, repeated treatment with FEWP, particularly at higher doses, reversed the aforementioned behavioral values in the elevated plus-maze and water maze tests to the levels similar to unexposed animals. These results indicate that FEWP possesses anxiolytic and cognition-improving effects and may be an effective herbal preparation for the treatment of stress-associated conditions, such as posttraumatic stress disorder (PTSD).

A modified single-prolonged stress model for post-traumatic stress disorder.

In the rat, single-prolonged stress (SPS) model produces a core symptom of post-traumatic stress disorder (PTSD), the enhanced fear response to the traumatic cue (conditioned fear response). This investigative tool is typically used for PTSD studies. However, whether SPS can produce another core symptom of PTSD, hyperarousal (the sensitized fear response in animal models), has not been evaluated. It is also not clear whether SPS can enhance both conditioned and sensitized fear responses after different incubation times. In this study, a single inescapable electric foot shock was given to rats immediately after SPS procedures (SPS&S). After different incubation times (1, 7 or 14 days), the conditioned or sensitized fear response was measured by re-exposing the stressed rats to the shock context or a neutral tone in a novel environment. Additionally, paroxetine, a selective serotonin reuptake inhibitor (SSRI) was administered after SPS&S for 14 days to test its potential preventive effect on PTSD-like symptoms. We observed that conditioned fear persisted and sensitized fear increased with ongoing incubation times after SPS&S. Early rapid intervention with paroxetine after SPS&S ameliorated PTSD-like symptoms in both fear responses and anxiety behaviors. Our data suggests that this modified SPS&S model may be both novel and predictably mimic the clinical characteristics of PTSD better than other investigative paradigms.

Differential effects of classical and atypical antipsychotic drugs on rotenone-induced neurotoxicity in PC12 cells.

Although classical and atypical antipsychotics may have different effects against neurotoxicity, the underlying mechanisms remain to be elucidated. In the present study, we compared the atypical agents, risperidone (RIP), olanzapine (OLZ), and quetiapine (QTP), with the classical agent haloperidol (HAL) in reducing cytotoxicity induced by rotenone, a mitochondrial complex I inhibitor, in PC12 cells. We also determined whether there were differential effects of RIP and HAL on the expression of brain-derived neurotrophic factor (BDNF), signal transducers and activators of transcription-3 (STAT-3), and the immediate early gene c-fos, as well as intracellular levels of calcium. Exposure to 6 muM rotenone for 24 h resulted in a significant decrease in cell viability and apoptotic alteration. The rotenone-induced cytotoxicity was dose-dependently worsened by pretreatment with HAL, but significantly improved by the aforementioned atypical agents at low doses. Real-time PCR analysis revealed that HAL pretreatment significantly increased BDNF mRNA expression but did not alter c-fos and STAT-3 expression compared to rotenone-exposed cells. Unlike HAL, RIP pretreatment produced a significant elevation of all the three substance mRNA expression and the expression intensity was 2.6- to 4.6-fold greater than HAL. Pretreatment with RIP, but not HAL, also effectively prevented an elevation of intracellular levels of calcium provoked by rotenone. These results suggest that the protective effects of atypical antipsychotics are associated with a greater capacity to enhance pro-cell survival factors, therapeutic biomarker expression, and blockade of calcium influx. This may provide an alternative for explaining therapeutic advantages of atypical agents observed in clinical use.