RS 10767664 gene variant in Brain Derived Neurotrophic Factor (BDNF) affect metabolic changes and insulin resistance after a standard hypocaloric diet

Background

Role of BDNF variants on change in body weight and cardiovascular risk factors after weight loss remains unclear in obese patients.

Dominant negative DISC1 mutant mice display specific social behaviour deficits and aberration in BDNF and cannabinoid receptor expression

Objectives. Disrupted in schizophrenia 1 (DISC1) is considered the most prominent candidate gene for schizophrenia. In this study, we aimed to characterize behavioural and brain biochemical traits in a mouse expressing a dominant negative DISC1mutant (DN-DISC1). Methods. DN-DISC1 mice underwent behavioural tests to evaluate object recognition, social preference and social novelty seeking. ELISA was conducted on brain tissue to evaluate BDNF levels. Western blot was employed to measure BDNF receptor (TrkB) and cannabinoid receptor CB1. Results. The mutant DISC1 mice displayed deficits in preference to social novelty while both social preference and object recognition were intact. Biochemical analysis of prefrontal cortex and hippocampus revealed a modest reduction in cortical TrkB protein levels of male mice while no differences in BDNF levels were observed. We found sex dependent differences in the expression of cannabinoid-1 receptors. Conclusions. We describe novel behavioural and biochemical abnormalities in the DN-DISC1 mouse model of schizophrenia. The data shows for the first time a possible link between DISC1 mutation and the cannabinoid system.     

Low serum BDNF levels in depressed patients cannot be attributed to individual depressive symptoms or symptom cluster

Objectives. Low serum BDNF levels have been found in depressed patients. No study has systematically investigated whether individual symptoms or symptom profiles within a depressed population contribute to low BDNF levels found in depressed subjects. Methods. All 1070 patients with a past 6-month diagnosis of major depressive disorder from the Netherlands Study of Depression and Anxiety (NESDA) were included. Composite International Diagnostic Interview (CIDI) and Inventory of Depressive Symptoms (IDS) items were tested individually in separate multiple regression analyses with serum BDNF level as the dependent and the CIDI or IDS item as independent variable. Subsequently, we compared BDNF levels between patients with seasonal affective disorder (based on the Seasonal Pattern Assessment Questionnaire) and melancholic depression, atypical depression and moderate depression (based on a latent class analysis). All analyses were adjusted for confounders. Results. Only one item was significantly associated with serum BDNF levels, namely the CIDI item “loss of interest” (β = 0.14; P < 0.01). Counterintuitively the presence of this symptom was associated with higher BDNF levels. Other items and the comparison between different types of depression did not reveal significant differences. Conclusions. Decreased serum BDNF levels in depression cannot be attributed to a specific symptom or symptom cluster.     

Stem cells in neuroinjury and neurodegenerative disorders： challenges and future neurotherapeutic prospects

The prevalence of neurodegenerative diseases and neural injury disorders is increasing worldwide. Research is now focusing on improving current neurogenesis techniques including neural stem cell therapy and other biochemical drug-based approaches to ameliorate these disorders. Unfortunately, we are still facing many obstacles that are rendering current neurotherapies ineffective in clinical trials for reasons that are yet to be discovered. That is why we should start by fully understanding the complex mechanisms of neurogenesis and the factors that affect it, or else, all our suggested therapies would fail since they would not be targeting the essence of the neurological disorder but rather the symptoms. One possible paradigm shift is to switch from neuroprotectant therapies towards neurodegeneration/neurorestorative approaches. In addition, other and our laboratories are increasingly focusing on combining the use of pharmacological agents（such as Rho-associated kinase（ROCK） inhibitors or other growth factors（such as brain-derived neurotrophic factor（BDNF）） and stem cell treatment to enhance the survivability and/or differentiation capacity of transplanted stem cells in neurotrauma or other neurodegeneration animal models. Ongoing stem cell research is surely on the verge of a breakthrough of multiple effective therapeutic options for neurodegenerative disorders. Once, we fully comprehend the process of neurogenesis and its components, we will fully be capable of manipulating and utilizing it. In this work, we discuss the current knowledge of neuroregenerative therapies and their associated challenges.     

Chronic Administration of Bacopa Monniera Increases BDNF Protein and mRNA Expressions: A Study in Chronic Unpredictable Stress Induced Animal Model of Depression

Objective

The present study aimed to investigate whether graded doses of Bacopa Monniera (BM) extract could produce antidepressant-like effects in chronic unpredictable stress (CUS) induced depression in rats and its possible mechanism(s).

Methods

Rats were subjected to an experimental setting of CUS. The effect of BM extract treatment in CUS-induced depression was examined using behavioral tests including the sucrose consumption, open field test and shuttle box escape test. The mechanism underlying the antidepressant-like action of BM extract was examined by measuring brain-derived neurotrophic factor (BDNF) protein and mRNA expression in brain tissues of CUS-exposed rats.

Results

Exposure to CUS for 4 weeks caused depression-like behavior in rats, as indicated by significant decreases in sucrose consumption, locomotor activity and escape latency. In addition, it was found that BDNF protein and mRNA levels in the hippocampus and frontal cortex were lower in CUS-treated rats, as compared to controls. Daily administration of the graded doses of BM extract during the 4-week period of CUS significantly suppressed behavioral changes and attenuated the CUS-induced decrease in BDNF protein and mRNA levels in the hippocampus and frontal cortex.

Conclusion

The results suggest that BM extract alleviates depression induced by CUS. Present study also confirms that 80-120 mg/kg doses of BM extract have significantly higher antidepressant-like activity.     

Concept and molecular basis of axonal regeneration after central nervous system injury

Damage to the central nervous system (CNS) leads to the disruption of the axonal network and causes neurological dysfunction. Recovery of neurological functions requires restoration of the axonal network; however, injured axons in the adult mammalian CNS rarely regenerate after injury. Failure of the injured axon to regenerate is attributed at least partly to the inhibitory molecules of the CNS: several proteins have been identified in the CNS that inhibit axonal regeneration. In addition, the molecular mechanisms underlying the manner via which these inhibitors prevent axonal regeneration have been clarified. The neutralization of nonpermissive substrate properties of the CNS has been shown to promote axonal regeneration in an animal model of CNS injury. Drugs that promote axonal regeneration, some of which have undergone clinical trials, have been developed by pharmaceutical companies. However, spontaneous functional recovery occurs sometimes after CNS injury. This review will describe the new concept of the molecular mechanism of restoration of the neuronal network, with a special focus on our recent reports.     

Sex Differences in the Behavioral,Molecular, and Structural Effects of Ketamine Treatment in Depression

Major depressive disorder (MDD) is a common psychiatric illness that manifests in sex-influenced ways. Men and women may experience depression differently and also respond to various antidepressant treatments in sex-influenced ways. Ketamine, which is now being used as a rapid-acting antidepressant, is likely the same. To date, the majority of studies investigating treatment outcomes in MDD do not disaggregate the findings in males and females, and this is also true for ketamine. This review aims to highlight that gap by exploring pre-clinical data—at a behavioral, molecular, and structural level—and recent clinical trials. Sex hormones, particularly estrogen and progesterone, influence the response at all levels examined, and sex is therefore a critical factor to examine when looking at ketamine response. Taken together, the data show females are more sensitive to ketamine than males, and it might be possible to monitor the phase of the menstrual cycle to mitigate some risks associated with the use of ketamine for females with MDD. Based on the studies reviewed in this article, we suggest that ketamine should be administered adhering to sex-specific considerations.     

DL-3-n-butylphthalide ameliorates diabetes-associated cognitive decline by enhancing PI3K/Akt signaling and suppressing oxidative stress

DL3-n-Butylphthalide(DLNBP),a small molecular compound extracted from the seeds of Ap/um graveo/ens Linn(Chinese celery),has been shown to exert neuroprotective effects due to its anti-inflammatory,anti-oxidative and anti-apoptotic activities.DL-NBP not only protects against ischemic cerebral injury,but also ameliorates vascular cognitive impairment in dementia patients including AD and PD.In the current study,we investigated whether and how DL-NBP exerted a neuroprotective effect against diabetes-associated cognitive decline(DACD)in db/db mice,a model of type-2 diabetes,db/db mice were orally administered DL-NBP(20,60,120 mg·kg^-1·d^-1)for 8 weeks.Then the mice were subjected to behavioral test,their brain tissue was collected for morphological and biochemical analyses.We showed that oral administration of DL-NBP significantly ameliorated the cognitive decline with improved learning and memory function in Morris water maze testing.Furthermore,DL-NBP administration attenuated diabetes-induced morphological alterations and increased neuronal survival and restored the levels of synaptic protein PSD95,synaptophysin and synapsin-1 as well as dendritic density in the hippocampus,especially at a dose of 60 mg/kg.Moreover,we revealed that DL-NBP administration suppressed oxidative stress by upregulating Nrf2/HO-1 signaling,and increased brain-derived neurotrophic factor(BDNF)expression by activating PI3K/Akt/CREB signaling in the hippocampus.These beneficial effects of DL-NBP were observed in high glucose-treated PC12 cells.Our results suggest that DL-NBP may be a potential pharmacologic agent for the treatment of DACD.     

逍遥丸对皮质酮诱导小鼠抑郁样行为的干预机制※

目的:观察逍遥丸对皮质酮诱导小鼠抑郁样行为的干预作用,并探讨其分子机制。方法:将50只ICR雄性小鼠,随机分为5组:正常组、皮质酮模型组、阳性对照氟西汀组(20 mg/kg)、低剂量逍遥丸(200 mg/kg)组、高剂量逍遥丸组(600 mg/kg),通过皮下注射皮质酮诱导小鼠抑郁模型。持续35天后,采用糖水偏好实验和强迫游泳实验评价动物抑郁样行为;采用ELISA方法测小鼠血清中皮质酮含量及小鼠海马组织中脑源性神经营养因子(BDNF)的含量。结果:皮质酮可以降低糖水偏好值、增加小鼠强迫游泳的不动时间,而逍遥丸可以显著提高糖水偏好值、减少小鼠不动时间;长期注射皮质酮可增加血清皮质酮水平,降低海马组织中BDNF含量,而逍遥丸可以降低小鼠血清中皮质酮的含量并且能够提高海马组织中BDNF含量。结论:逍遥丸可以有效降低小鼠血清中皮质酮的含量并增加小鼠海马中BDNF含量,改善神经营养系统,产生抗抑郁样作用。     

越鞠丸联合盐酸氟西汀胶囊治疗抑郁症临床研究

目的:观察越鞠丸联合盐酸氟西汀胶囊治疗抑郁症的临床效果及对血清脑源性神经营养因子(BDNF)水平的影响。方法:纳入因抑郁症就诊的64例患者,随机分为对照组与治疗组各32例。对照组给予盐酸氟西汀胶囊抗5-羟色胺(5-HT)治疗,治疗组在对照组基础上联合越鞠丸治疗。比较2组治疗前后汉密尔顿抑郁量表(HAMD-24)评分、抑郁症状学快速自评量表(QIDS-SR16)、血清BDNF水平及总体疗效。结果:治疗前后比较,2组HAMD-24评分、QIDS-SR16评分均下降,血清BDNF水平升高(P<0.05),组间比较,治疗组2项评分下降更多,血清BDNF水平升高更多(P<0.05)。治疗后,治疗组总体疗效为90.63%,优于对照组的68.75%,差异有统计学意义(P<0.05)。结论:越鞠丸联合盐酸氟西汀胶囊治疗抑郁症,可更加有效减缓患者抑郁症状,升高血清BDNF水平,增加临床疗效,有效保护患者脑功能,值得临床推广。