香萱益神方对血管性痴呆模型大鼠神经元凋亡机制研究

目的:探讨香萱益神方治疗血管性痴呆(VD)模型大鼠认知功能作用及其对神经元凋亡机制的研究。方法:两血管阻断法建立VD大鼠模型,给予中药方香萱益神方灌胃治疗6周,分别于造模后、中药喂养6周后进行Morris水迷宫行为学检测,测试大鼠认知行为能力改变,行为学测试结束后,检测VD模型大鼠海马中海马组织脑源性神经营养因子(BDNF)表达水平的变化。结果:香萱益神方治疗6周后,血管性痴呆大鼠模型学习记忆能力得到改善,上调脑内海马组织神经营养因子水平,海马神经元凋亡率下降。结论:香萱益神方是治疗血管性痴呆的有效方剂,可以有效改善VD大鼠模型认知行为功能的障碍情况,起到减少海马神经元细胞凋亡,诱导海马神经元细胞修复的作用。香萱益神方可能是通过激活BDNF相关通路,起到保护海马神经元的作用。     

胶质细胞源性神经营养因子干预视网膜色素变性给药方式的研究进展

视网膜色素变性（retinitis pigmentosa，RP）的治疗目前仍处于探索阶段。胶质细胞源性神经营养因子（glial cell line-derived neurotrophic factor，GDNF）是目前研究中重要的神经营养因子，但其传统给药方式生物利用度相对较低。近年来GDNF安全有效的给药方式成为研究热点，包括经病毒载体或非病毒载体的基因工程法释药技术、经聚合物释放系统释药技术、经细胞移植释药技术、小分子触发器诱导产生GDNF等。本文就GDNF干预RP的给药方式进行综述。     

首发儿童精神分裂症患者脑源性神经营养因子水平及神经元凋亡研究

目的探讨首发儿童精神分裂症患者脑源性神经营养因子(BDNF)、β-微管蛋白III(Tuj-1)、胱天蛋白酶3(Caspase-3)的变化,为揭示儿童精神分裂症的病因和发病机制提供参考。方法以2015年8月-2018年3月在大理州第二人民医院就诊的符合《精神障碍诊断与统计手册(第4版)》(DSM-IV)诊断标准的儿童精神分裂症患者(n=35)为研究组,同期在大理州第二人民医院的体检儿童中随机选取健康儿童为对照组(n=30)。通过实时荧光定量逆转录-聚合酶链反应(RT-PCR)测定两组儿童血液中BDNF、Caspase-3和Tuj-1的mRNA表达水平。结果与对照组相比,研究组BDNF和Tuj-1 mRNA表达低(P0.05或0.01),Caspase-3 mRNA表达高(P0.01)。结论儿童精神分裂症患者的BDNF mRNA和Tuj-1 mRNA表达少,Caspase-3 mRNA表达多,BDNF mRNA、Tuj-1 mRNA和Caspase-3 mRNA可能与儿童精神分裂症相关。     

Paired associated magnetic stimulation promotes neural repair in the rat middle cerebral artery occlusion model of stroke

Paired associative stimulation has been used in stroke patients as an innovative recovery treatment. However, the mechanisms underlying the therapeutic effectiveness of paired associative stimulation on neurological function remain unclear. In this study, rats were randomly divided into middle cerebral occlusion model(MCAO) and paired associated magnetic stimulation(PAMS) groups. The MCAO rat model was produced by middle cerebral artery embolization. The PAMS group received PAMS on days 3 to 20 post MCAO. The MCAO group received sham stimulation, three times every week. Within 18 days after ischemia, rats were subjected to behavioral experiments—the foot-fault test, the balance beam walking test, and the ladder walking test. Balance ability was improved on days 15 and 17, and the footfault rate was less in their affected limb on day 15 in the PAMS group compared with the MCAO group. Western blot assay showed that the expression levels of brain derived neurotrophic factor, glutamate receptor 2/3, postsynaptic density protein 95 and synapsin-1 were significantly increased in the PAMS group compared with the MCAO group in the ipsilateral sensorimotor cortex on day 21. Resting-state functional magnetic resonance imaging revealed that regional brain activities in the sensorimotor cortex were increased in the ipsilateral hemisphere, but decreased in the contralateral hemisphere on day 20. By finite element simulation, the electric field distribution showed a higher intensity, of approximately 0.4 A/m~2, in the ischemic cortex compared with the contralateral cortex in the template. Together, our findings show that PAMS upregulates neuroplasticity-related proteins, increases regional brain activity, and promotes functional recovery in the affected sensorimotor cortex in the rat MCAO model. The experiments were approved by the Institutional Animal Care and Use Committee of Fudan University, China(approval No. 201802173 S) on March 3, 2018.     

Brain-derived neurotrophic factor and inflammation in depression: Pathogenic partners in crime?

Major depressive disorder is a debilitating disorder affecting millions of people each year. Brain-derived neurotrophic factor (BDNF) and inflammation are two prominent biologic risk factors in the pathogenesis of depression that have received considerable attention. Many clinical and animal studies have highlighted associations between low levels of BDNF or high levels of inflammatory markers and the development of behavioral symptoms of depression. However, less is known about potential interaction between BDNF and inflammation, particularly within the central nervous system. Emerging evidence suggests that there is bidirectional regulation between these factors with important implications for the development of depressive symptoms and anti-depressant response. Elevated levels of inflammatory mediators have been shown to reduce expression of BDNF, and BDNF may play an important negative regulatory role on inflammation within the brain. Understanding this interaction more fully within the context of neuropsychiatric disease is important for both developing a fuller understanding of biological pathogenesis of depression and for identifying novel therapeutic opportunities. Here we review these two prominent risk factors for depression with a particular focus on pathogenic implications of their interaction.     

六味地黄汤干预抑郁大鼠学习记忆的作用机制

目的:探讨六味地黄汤对慢性抑郁大鼠记忆障碍的改善作用,并探讨其可能的作用机制。方法:Wistar雌性大鼠随机分为正常组(生理盐水)、慢性不可预见性温和应激(CUMS)模型组(生理盐水)、六味地黄汤低、中、高剂量组(2. 60,7. 81,23. 50 g·kg~(-1)·d~(-1))。除正常组外,其余各组造成CUMS模型。每周称体质量,观察其行为学指标变化;实时荧光定量聚合酶链式反应(Real-time PCR)检测其海马G蛋白偶联雌激素受体(GPR30),胞内磷脂酰肌醇激酶(PI3K),环磷酸腺苷反应元件结合蛋白(CREB),脑源性神经营养因子(BDNF) mRNA的表达;酶联免疫吸附测定(ELISA)检测血清中雌激素含量。结果:与正常组比较,模型组体质量、活动能力、兴趣等明显降低(P 0. 05,P 0. 01);与模型组比较,六味地黄汤2. 60,7. 81,23. 50 g·kg~(-1)可明显提高CUMS大鼠糖水偏好度(P 0. 01)和旷场实验的站立次数(P 0. 01);7. 81,23. 50 g·kg~(-1)明显提高旷场实验的总距离(P 0. 05,P 0. 01);2. 60,7. 81 g·kg~(-1)可缩短水迷宫实验寻台潜伏期(P 0. 01);7. 81 g·kg~(-1)可增加血清中雌激素含量(P 0. 05);CUMS模型组大鼠海马组织内的GPR30,PI3K,CREB,BDNF mRNA表达明显下降(P 0. 05,P 0. 01),六味地黄汤2. 60 g·kg~(-1)显著增加海马组织内的GPR30,CREB mRNA表达(P 0. 05,P 0. 01),7. 81 g·kg~(-1)明显增加海马组织内的GPR30,PI3K,CREB,BDNF mRNA表达量(P 0. 05,P 0. 01)。结论:六味地黄汤具有抗抑郁作用,逆转CUMS大鼠抑郁样行为及学习记忆障碍,其中中剂量组药效最显著。其作用机制可能与增加血清中雌激素和提高大鼠海马GPR30,PI3K,CREB,BDNF mRNA表达有关。     

Does obesity put your brain at risk?

Background and aimsThe negative impact of obesity on the brain is an issue of increasing clinical interest. Hence, this review summarized evidence linking obesity with brain morphology (gray and white matter volume), brain function (functional activation and connectivity), and cognitive function.MethodsA criticals review of the relevant published English articles between 2008 and 2022, using PubMed, Google Scholar and Science Direct. Studies were included if (1) an experimental/intervention study was conducted (2) the experiment/intervention included both high fat diet or body weight, whether it could counteract the negative effect brain morphological or functional change. Critical analysis for a supporting study was also carried out.ResultsBrain dysfunction can be recognized as result from neuroinflammation, oxidative stress, change in gut-brain hormonal functionality decrease regional blood flow or diminished hippocampal size and change in gut-brain hormonal functionality; which collectively translate into a cycle of deranged metabolic control and cognitive deficits, often obesity referred as changes in brain biochemistry and brain function. Recently, a few changes in brain structure and functions could be traced back even to obese children or adult. Evidence here suggested that obesity elicits early neuroinflammation effects, which likely disrupt the normal metabolism in hypothalamus, and hippocampus result from brain insulin resistance. The mechanisms of these robust effects are discussed herein.ConclusionBrain disease is inseparable from obesity itself and requires a better recognition to allow future therapeutic targeting for treatment of obesity. Additional research is needed to identify the best treatment targets and to identify if these changes reversible.     

Acute and subsequent continuation electroconvulsive therapy elevates serum BDNF levels in patients with major depression

IntroductionThe induction of brain-derived neurotrophic factor (BDNF) release and subsequent restoration of neuroplastic homeostasis may underlie the effects of electroconvulsive therapy (ECT).ObjectivesWe aimed to assess serum and plasma BDNF levels during the course of acute ECT, as well as before and after subsequent continuation ECT, in patients with depression.MethodsWe included 24 patients with major depressive disorder (mean age ± SD: 54.5 ± 13.7; f/m: 17/7; baseline 17-item Hamilton Depression Rating Scale score of 26.79 ± 4.01). Serum and plasma BDNF (sBDNF, pBDNF) levels were assessed at nine time-points before, during, and after acute ECT series. Data were analysed using linear regression and linear mixed models, which were adjusted for multiple comparisons via Bonferroni correction. Five patients received continuation ECT subsequent to the acute ECT series. In these patients, BDNF levels were assessed before and after each two continuation ECT sessions using Wilcoxon signed-rank tests.ResultsRelative to baseline (mean ng/ml ±SD: 24.68 ± 14.40), sBDNF levels were significantly higher 1 day (33.04 ± 14.11, p = 0.013, corrected), 1 week (37.03 ± 10.29, p < 0.001, corrected), and 1 month (41.05 ± 10.67, p = 0.008, corrected) after the final ECT session, while pBDNF levels did not significantly differ (p > 0.1). Furthermore, our results indicated that sBDNF levels increased after each continuation ECT session. There was no significant association between sBDNF levels and clinical parameters or treatment response.ConclusionThe absence of an association between changes in sBDNF levels and depressive symptoms challenges the proposed concept of sBDNF/pBDNF as key markers of the effects of ECT.