山茱萸多糖对青霉素致痫幼鼠学习记忆能力及海马组织脑源性神经因子、神经生长因子表达的影响

目的:探讨山茱萸多糖对青霉素致痫幼鼠学习记忆能力及海马组织脑源性神经因子(BDNF)、神经生长因子(NGF)表达的影响。方法:将30只日龄21 d龄幼鼠随机分为生理盐水对照组、青霉素点燃模型组、山茱萸多糖处理组各10只。生理盐水对照组只接受生理盐水灌胃,不造模;山茱萸多糖处理组在造模成功后灌胃0.05 g/mL山茱萸多糖;青霉素点燃模型组造模成功后灌胃等量生理盐水;连续灌胃28 d。采用Morris水迷宫检测各组幼鼠学习记忆能力;RT-PCR法检测海马组织BDNF mRNA、NGF mRNA表达;Western-blot法检测海马组织BDNF与NGF蛋白含量。结果:与生理盐水对照组比较,青霉素点燃模型组幼鼠学习记忆能力明显降低(P<0.01);与模型组比较,山茱萸多糖处理组学习记忆能力明显升高(P<0.01)。与生理盐水对照组比较,青霉素点燃模型组幼鼠BDNF、NGF mRNA和蛋白表达明显降低(P<0.01);与模型组比较,山茱萸多糖处理组BDNF、NGF mRNA和蛋白表达明显升高(P<0.01)。结论:山茱萸多糖具有提高青霉素点燃幼鼠学习记忆能力的作用,其机制可能是通过上调BDNF和NGF基因表达。     

A Combined Metabonomic and Proteomic Approach Identifies Frontal Cortex Changes in a Chronic Phencyclidine Rat Model in Relation to Human Schizophrenia Brain Pathology

Current schizophrenia (SCZ) treatments fail to treat the broad range of manifestations associated with this devastating disorder. Thus, new translational models that reproduce the core pathological features are urgently needed to facilitate novel drug discovery efforts. Here, we report findings from the first comprehensive label-free liquid-mass spectrometry proteomic- and proton nuclear magnetic resonance-based metabonomic profiling of the rat frontal cortex after chronic phencyclidine (PCP) intervention, which induces SCZ-like symptoms. The findings were compared with results from a proteomic profiling of post-mortem prefrontal cortex from SCZ patients and with relevant findings in the literature. Through this approach, we identified proteomic alterations in glutamate-mediated Ca²⁺ signaling (Ca²⁺/calmodulin-dependent protein kinase II, PPP3CA, and VISL1), mitochondrial function (GOT2 and PKLR), and cytoskeletal remodeling (ARP3). Metabonomic profiling revealed changes in the levels of glutamate, glutamine, glycine, pyruvate, and the Ca²⁺ regulator taurine. Effects on similar pathways were also identified in the prefrontal cortex tissue from human SCZ subjects. The discovery of similar but not identical proteomic and metabonomic alterations in the chronic PCP rat model and human brain indicates that this model recapitulates only some of the molecular alterations of the disease. This knowledge may be helpful in understanding mechanisms underlying psychosis, which, in turn, can facilitate improved therapy and drug discovery for SCZ and other psychiatric diseases. Most importantly, these molecular findings suggest that the combined use of multiple models may be required for more effective translation to studies of human SCZ.     

阿立哌唑治疗精神分裂症对患者认知功能和神经营养因子的影响

目的:探讨阿立派唑治疗精神分裂症对患者认知功能和神经营养因子(NT)的影响.方法:选取2019年9月至2020年6月在商丘市第二人民医院治疗的75例精神分裂症患者,随机抽签分为对照组(38例)与观察组(37例).对照组口服利培酮,观察组使用阿立派唑片治疗,比较两组治疗前后精神分裂症认知功能成套测验(MCCB)评分及血清...     

二苯乙烯苷对D-半乳糖致脑老化小鼠学习记忆及神经营养因子的影响

目的 :观察何首乌提取物二苯乙烯苷 (TSG)对D -半乳糖致痴呆模型小鼠学习记忆及脑内神经营养因子表达的影响。方法 :将小鼠随机分为正常对照组、D -半乳糖模型组、VitE阳性对照组及TSG低、中、高剂量 (0 033、0 1、0 3g/kg)6个组 ,除正常对照组外 ,其余各组小鼠在建立脑老化模型的同时灌胃给予相应药物60d ,随后进行Morris水迷宫测试 ,并采用免疫组化的方法检测TSG对神经生长因子 (NGF)和神经营养因子 -3(NT -3)的影响。结果 :与正常对照组比较 ,模型组小鼠在Morris水迷宫测试中游出时间和游出距离延长 ,海马CA1区NGF和NT -3的表达明显减少 ;TSG则能缩短小鼠游出时间和游出距离 ,增加海马CA1区NGF和NT -3的表达。结论 :TSG能明显提高学习记忆能力 ,对阿尔茨海默病可能具有防治作用。     

蝎毒注射液对阿尔茨海默病模型大鼠学习记忆能力及海马BDNF/TrkB表达的影响

目的：探讨蝎毒注射液（scorpion venom injection,SVI）对阿尔茨海默病（Alzheimer’s disease,AD）模型大鼠的学习记忆能力以及海马组织中脑源性神经营养因子（brain-derived neurotrophic factor,BDNF）和酪氨酸激酶受体B （tyrosine kinase receptor B,TrkB）表达的影响。方法： 36只智力正常的健康成年SD大鼠,每组12只,随机分为正常对照组、AD模型组与SVI治疗组。后两组采用双侧海马注射Aβ_25-35构建AD模型,SVI治疗组于造模后每日一次腹腔注射SVI,连续10 d。Morris水迷宫测试各组大鼠认知功能,之后取大鼠海马组织,RT-PCR法、免疫组化和Western Blot法分别检测海马组织中BDNF与TrkB的mRNA和蛋白表达情况。结果：与对照组相比,AD模型组大鼠认知能力降低,逃避潜伏期延长,空间探索次数减少,海马中BDNF、TrkB的mRNA和蛋白表达水平明显降低（P<0.05）。而与AD模型组相比,SVI治疗组大鼠的逃避潜伏期缩短,空间探索次数增加,海马中BDNF与TrkBmRNA和蛋白表达水平显著升高（P<0.05）。结论： SVI能够改善AD模型大鼠学习记忆能力,可能与激活脑内BDNF-TrkB信号通路、提高海马组织中BDNF和TrkB表达有关。     

七氟烷和异氟烷急性暴露对SD幼大鼠学习记忆及海马脑源性神经营养因子表达的影响

目的探讨挥发性麻醉药七氟烷和异氟烷急性暴露对SD大鼠幼年期学习记忆及海马脑源性神经营养因子(BDNF)表达的影响及其机制。方法 7日龄大鼠提前0.5 h ip给予荷包牡丹碱8 mg.kg-1或蝇蕈醇1 mg.kg-1,然后暴露于含3.6%七氟烷或2.3%异氟烷的空氧混合气中,连续6 h。出生后第21天时行Morris水迷宫实验记录潜伏期;取海马,免疫组化及Western印迹法检测γ氨基丁酸-A(GABA-A)受体α1亚基和BDNF表达,逆转录-PCR方法检测mRNA表达。结果 氟烷组的连续5 d总潜伏期均显著延长(P<0.05);与七氟烷和异氟烷组比,提前给予荷包牡丹碱或蝇蕈醇对潜伏期无显著改善作用。免疫组化、Western印迹法和逆转录-PCR结果显示,与正常对照组相比,七氟烷、异氟烷和提前给予荷包牡丹碱或蝇蕈醇组幼鼠海马GABA-A受体α1亚基蛋白与mRNA表达无明显差异;七氟烷和异氟烷组BDNF的蛋白和mRNA表达量显著降低,分别降低了13%,25%和23%,21%(P<0.05)。与七氟烷和异氟烷组相比,提前给予荷包牡丹碱或蝇蕈醇组BDNF的蛋白和mRNA表达量无显著差异。结论 七氟烷和异氟烷急性暴露能够影响SD大鼠幼年期学习记忆功能,可能与BDNF的表达改变有关,GABA-A受体不参与神经发育毒性的介导。     

Electrophysiological Effects of Repeated Administration of Agomelatine on the Dopamine,Norepinephrine, and Serotonin Systems in the Rat Brain

Agomelatine is a melatonergic MT1/MT2 agonist and a serotonin (5-HT) 5-HT_2C antagonist. The effects of 2-day and 14-day administration of agomelatine were investigated on the activity of ventral tegmental area (VTA) dopamine (DA), locus coeruleus (LC) norepinephrine (NE), and dorsal raphe nucleus (DRN) 5-HT neurons using in vivo electrophysiology in rats. The 5-HT_1A transmission was assessed at hippocampus CA3 pyramidal neurons. After a 2-day regimen of agomelatine (40 mg/kg/day, i.p.), an increase in the number of spontaneously active VTA-DA neurons (p<0.001) and in the firing rate of LC-NE neurons (p<0.001) was observed. After 14 days, the administration of agomelatine induced an increase in: (1) the number of spontaneously active DA neurons (p<0.05), (2) the bursting activity of DA neurons (bursts/min, p<0.01 and percentage of spikes occurring in bursts, p<0.05), (3) the firing rate of DRN-5-HT neurons (p<0.05), and (4) the tonic activation of postsynaptic 5-HT_1A receptors located in the hippocampus. The increase in 5-HT firing rate was D2 dependent, as it was antagonized by the D2 receptor antagonist paliperidone. The enhancement of NE firing was restored by the 5-HT_2A receptor antagonist MDL-100,907 after the 14-day regimen. All the effects of agomelatine were antagonized by a single administration of the melatonergic antagonist {"type":"entrez-protein","attrs":{"text":"S22153","term_id":"100005","term_text":"pir||S22153"}}S22153 (except for the increase in the percentage of spikes occurring in burst for DA neurons). The present results suggest that (1) agomelatine exerts direct (2 days) and indirect (14 days) modulations of monoaminergic neuronal activity and (2) the melatonergic agonistic activity of agomelatine contributes to the enhancement of DA and 5-HT neurotransmission.     

Adenylate Cyclase in Rat Synaptosomal Plasma Membranes and Caudate Nucleus Homogenate: Effects of Dopamine,E Prostaglandins,Guanyl-5′-yl-imidodiphosphate and Morphine

Abstract: The adenylate cyclase in two particulate preparations from rat brain, a homogenate from caudate nucleus (CN-homogenate) and a synaptosomal plasma membrane fraction (SPM-fraction) from whole rat brain was investigated. Stimulation of the enzyme by dopamine and prostaglandins E₁ and E₂ was found in the CN-homogenate while only a weak prostaglandin E₁ and E₂ stimulation and no dopamine stimulation could be found in the SPM-fraction. Guanyl-5′-yl-imidophosphate (GppNHp) and NaF could stimulate the adenylate cyclase in both preparations. Morphine up to 10^–5 M altered neither the basal enzyme activity nor any of the stimulated enzyme activities.     

鼠神经生长因子对早产儿脑损伤血清神经损伤标志物和神经行为学的影响

目的探究和分析鼠神经生长因子对早产儿脑损伤血清神经损伤标志物和神经行为学的影响。方法选取河南省人民医院2016年2月-2018年2月早产脑损伤患儿160例,随机分为对照组和观察组,每组各80例,对照组使用常规治疗方法并每日静脉滴注胞二磷胆碱钠注射液,观察组在对照组基础上加用鼠神经生长因子肌肉注射,评估疗效、神经行为,分别检测治疗前后血清糖分解烯醇酶(serum neuron-specific enolase,NSE)、胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)、髓鞘碱性蛋白(myelin basic protein,MBP)、S100钙结合蛋白β(S100 calcium-binding proteinβ,S-100β)和Toll样受体-4(Toll-like receptor-4,TLR-4)的含量,并观察治疗期间不良反应发生情况。结果观察组改善率为93.75%,对照组改善率为72.50%,明显低于观察组(χ^2=16.10,P<0.05);治疗后2组各项新生儿神经行为测定评分均明显升高(P<0.05),观察组较对照组更明显(P<0.05);2组治疗后NSE、GFAP、MBP、S-100β和TLR-4较治疗前明显下降(P<0.05),观察组较对照组更明显(P<0.05);对照组和观察组不良反应发生情况差异不显著。结论鼠神经生长因子治疗能明显提升脑损伤早产儿临床疗效,改善各项血清学指标,改善患儿神经行为,且临床用药安全。     

天麻多糖与电针对脑缺血大鼠齿状回BDNF和 VEGF表达的影响

目的：观察天麻多糖与电针对脑缺血大鼠齿状回（dentate gyrus,DG） 脑源性神经营养因子（brain derived neurotrophic factor,BDNF）和血管内皮生长因子（vascular endothelial growth factor,VEGF）表达的影响。方法：将40只SD大鼠随机分为正常对照组、模型组、电针组、天麻多糖组和针药结合组,每组8只。以单侧大脑中动脉栓塞法制备脑缺血模型。造模后2周,天麻多糖组和针药结合组大鼠给予天麻多糖 100 mg/kg灌胃,每天1次,连续2周;电针组和针药结合组大鼠给予“百会”、“足三里”穴电针刺激,持续 30 min,每天1次,连续2周。采用免疫组织化学染色法结合图像分析检测DG BDNF和VEGF的表达。结果：与正常对照组比较,模型组缺血侧DG BDNF和VEGF阳性表达增加（P〈0.05）;与模型组比较,电针组、天麻多糖组和针药结合组缺血侧DG BDNF和VEGF阳性表达明显增加（P〈0.05） ;针药结合组阳性表达显著多于电针组或天麻多糖组（P〈0.01）。结论：天麻多糖与电针结合可显著增加脑缺血大鼠缺血侧DG BDNF和VEGF的表达,促进内源性神经干细胞激活,且作用优于单用电针或天麻多糖。     

Adolescent Atomoxetine Treatment in a Rodent Model of ADHD: Effects on Cocaine Self-Administration and Dopamine Transporters in Frontostriatal Regions

Cocaine abuse and attention deficit/hyperactivity disorder (ADHD) are often comorbid. Preclinical research indicates that medial prefrontal (mPFC) and orbitofrontal (OFC) cortices are important neural substrates for both disorders. Using the spontaneously hypertensive rat (SHR) model of ADHD, we reported that adolescent treatment with the stimulant methylphenidate, a dopamine (DAT) and norepinephrine (NET) transporter inhibitor, enhanced cocaine self-administration during adulthood, and was associated with increased DAT function in mPFC. This study investigates the effects of atomoxetine ((R)-N-methyl-γ-(2-methylphenoxy)-benzenepropanamine hydrochloride) treatment, a selective NET inhibitor, during adolescence on cocaine self-administration and on DAT function and cell-surface expression in mPFC and OFC during adulthood. SHR acquired cocaine self-administration faster than Wistar–Kyoto and Wistar. Across cocaine doses, SHR earned more cocaine infusions and had higher progressive-ratio breakpoints than Wistar–Kyoto and Wistar, demonstrating that the SHR phenotype models comorbid ADHD and cocaine abuse. Prior atomoxetine treatment did not augment cocaine self-administration in SHR, but acquisition was enhanced in Wistar–Kyoto. No strain differences were found for DAT kinetic parameters or cellular localization in the vehicle controls. Atomoxetine did not alter DAT kinetic parameters or localization in SHR mPFC. Rather, atomoxetine decreased V_max and DAT cell surface expression in SHR OFC, indicating that inhibition of NET by atomoxetine treatment during adolescence indirectly reduced DAT function and trafficking to the cell surface in OFC, specifically in the ADHD model. Thus, atomoxetine, unlike methylphenidate, does not enhance vulnerability to cocaine abuse in SHR and may represent an important alternative for teens with ADHD when drug addiction is a concern.     

美满霉素对阿尔茨海默病大鼠认知损伤及海马 BDNF、 Bcl-2 和 Bax 表达的影响

目的 观察美满霉素对阿尔茨海默病（AD）大鼠认知功能和海马脑源性神经营养因子（BDNF）、凋亡相关因子 Bcl-2 和 Bax 表达的影响, 探讨美满霉素对 AD 大鼠脑保护作用的机制。 方法 侧脑室注射 Aβ25-35 建立 AD 大鼠模型。 30 只健康雄性 SD 大鼠随机分成对照组、模型组和治疗组, 每组 10 只。 对照组和模型组腹腔内注射生理盐水 1 mL/（kg· d）, 治疗组腹腔注射美满霉素 50 mg/（kg· d）, 均持续 14 d。 Morris 水迷宫检测行为学变化, 蛋白免疫印迹（Western blotting）法和酶联免疫吸附试验（ELISA）法检测海马 BDNF、Bcl-2 和 Bax 蛋白的表达, 原位末端标记（TUNEL）法检测海马神经元凋亡率。 结果 美满霉素可以明显提高 AD 大鼠学习记忆能力, 上调 AD 大鼠海马 BDNF、Bcl-2 表达, 下调 Bax 表达, 减少海马神经元凋亡。 结论 美满美素可以通过促进神经元的生长、抑制神经元的凋亡发挥脑保护作用。