东莨菪碱慢性给药大鼠作为老龄相关记忆损害模型的探索

目的对东莨菪碱慢性给药大鼠能否作为老龄相关记忆损害模型进行探索。方法14只1月龄SD大鼠随机分为对照组和东莨菪碱模型组。东莨菪碱模型组大鼠皮下注射东莨菪碱2mg kg,2次日,正常对照组予等量生理盐水,连续21d。然后利用Morris水迷宫(MWM)参照记忆试验进行行为学测试;神经元的特殊染色及电子显微镜技术,观察大鼠海马CA1、CA3区锥体细胞数、超微结构的改变以及突触可塑性变化。结果东莨菪碱组大鼠隐匿平台搜索实验成绩有一定损害;两组大鼠空间探索次数差异无显著性(P>0.05)。两组间海马CA1、CA3区锥体细胞数差异无显著性(P>0.05)。两组大鼠锥体细胞胞体超微结构无差异,但两组大鼠CA1区神经元突触超微结构有轻微变化。结论东莨菪碱慢性给药对大鼠学习记忆能力有一定损害,但对长时记忆无明显影响;对海马神经元结构无明显损害,对神经元突触可塑性有轻微影响。此种动物模型可能不是理想的老年性痴呆或老年相关记忆损害模型。     

银杏内酯对拟Alzheimer病样大鼠学习记忆的影响

目的:观察银杏内酯对拟Alzheimer病大鼠学习、记忆的影响。方法:大鼠海马背侧微量注射0.4mmol/LOkadiacAcid(OA)0.6μl,每两天一次,连续三次,造模。银杏内酯治疗组与模型制作同时开始,每只每天腹腔注射银杏内酯(50mg/kg),连续注射21天。海马背侧首次微量注射20天后,测试各组大鼠空间学习记忆能力,大鼠海马冠状切片HE染色。结果:银杏治疗组较模型组大鼠空间学习记忆能力明显增强,HE染色显示银杏内酯治疗组神经元变性及坏死较模型组减少明显。结论:银杏内酯可提高拟Alzheimer病模型鼠的学习、记忆能力。     

不同年龄大鼠学习记忆能力及旷场行为比较

目的：实验对２２日龄、１月龄、５月龄、１０月龄、２４月龄的ＳＤ大鼠的行为学进行比较。方法：采用水迷宫及旷场分析法对上述五种不同年龄组的大鼠进行研究,数据采用多因素方差分析处理。结果：幼鼠（２２日龄、１月龄）及老年鼠（２４月龄）游泳所用时间及错误次数比成年鼠（５月龄、１０月龄）多,差异显著（Ｐ＜０．０５）。幼鼠及老年鼠的空间认知能力显著低于成年鼠,并且对新异环境的适应性差,更加紧张（Ｐ＜０．０５）。结论：动物的学习记忆能力,空间认知能力及兴奋性存在着年龄上的差异,青壮年大鼠学习记忆能力及对新异环境的适应性均强于幼年及老年大鼠     

高血流切应力对老年大鼠后肢侧支血管管壁平滑肌的影响

目的利用股动脉结扎加股动静脉吻合和单纯股动脉结扎的侧支血管生长模型探讨高血流切应力对老年大鼠后肢侧支血管管壁平滑肌的影响。方法成年大鼠10只及老年大鼠15只,随机分为成年大鼠假手术组、成年大鼠股动脉结扎组、老年大鼠假手术组、老年大鼠股动脉结扎组和老年大鼠股动脉结扎加动静脉吻合组。结扎组行股动脉结扎手术。动静脉吻合组则在股动脉结扎后,将股动脉结扎远侧端与伴随的股静脉行吻合术。动物术后存活1周后,采用免疫荧光组织化学法检测肌球蛋白重链(myosin heavy chain,MHC)和波形蛋白(vimentin)在侧支血管管壁的表达变化。结果与老年大鼠假手术组相比,老年大鼠股动脉结扎组的后肢侧支血管壁vimentin的表达增强,MHC的表达下降;与老年大鼠股动脉结扎组相比,老年大鼠股动脉结扎加股动静脉吻合组的后肢侧支血管壁vimentin的表达显著增强,MHC的表达下降。结论高血流切应力使老年大鼠缺血后肢侧支血管管壁的平滑肌由收缩表型向合成表型转变。     

天麻多糖结合电针抑制脑缺血大鼠Meynert基底核神经元损伤和上调BDNF、SCF及VEGF表达

目的观察脑缺血后Meynert基底核BDNF、SCF及VEGF等的表达,比较分析天麻多糖(gastrodia elata polysaccharide,GEP))结合电针(electroacupuncture,EA)或单独应用对其干预效果,探讨针药结合对脑缺血的神经血管保护机制。方法将雄性SD大鼠40只随机分成空白对照组、脑缺血模型组、天麻多糖组、电针组及针药结合组,每组8只。采用单侧大脑中动脉线栓法制备局灶性脑缺血大鼠模型。模型制备成功后,天麻多糖组大鼠每日给予天麻多糖100mg/kg灌胃1次,连续2周;电针组大鼠每日电针刺激"百会"、"足三里"穴1次,每次30min,连续2周;针药结合组每日电针刺激"百会"、"足三里"穴1次,每次30min,同时给予天麻多糖100mg/kg灌胃1次,连续2周。尼氏染色法观察各组大鼠Meynert基底核神经细胞形态及存活数,免疫组织化学方法检测各组大鼠Meynert基底核BDNF、SCF及VEGF蛋白的表达情况。结果与正常组比较,模型组大鼠缺血侧Meynert基底核神经细胞存活数显著减少,BDNF、SCF及VEGF免疫染色显著增强;与模型组比较,天麻多糖组、电针组及针药结合组大鼠缺血侧Meynert基底核神经细胞存活数显著增加,BDNF、SCF及VEGF免疫染色显著增强;针药结合组与天麻多糖组、电针组比较,缺血侧Meynert基底核神经细胞存活数显著增加,BDNF、SCF及VEGF免疫染色也增强。结论脑缺血后Meynert基底核神经血管相关因子表达增加,提示Meynert基底核是脑缺血后易损区域之一;天麻多糖结合电针可上调BDNF、SCF及VEGF表达,对Meynert基底核起到神经的保护作用,且作用优于天麻多糖或电针的单独应用。     

银杏内酯对拟Alzheimer病样大鼠学习记忆的影响

目的：观察银杏内酯对拟Alzheimer病大鼠学习、记忆的影响。方法：大鼠海马背侧微量注射0．4mmol/LOkadiac Acid(OA)0.6μl,每两天一次,连续三次,造模。银杏内酯治疗组与模型制作同时开始,每只每天腹腔注射银杏内酯(50mg／kg),连续注射21天。海马背侧首次微量注射20天后,测试各组大鼠空间学习记忆能力,大鼠海马冠状切片HE染色。结果：银杏治疗组较模型组大鼠空间学习记忆能力明显增强,HE染色显示银杏内酯治疗组神经元变性及坏死较模型组减少明显。结论：银杏内酯可提高拟Alzheimer病模型鼠的学习、记忆能力。     

第四脑室注射orexin-A及OX1R拮抗剂对大鼠摄食及自由活动的影响

本文旨在探讨第四脑室注射orexin-A及orexin 1型受体(orexin-1 receptor,OX1R)拮抗剂SB334867对肥胖和正常大鼠摄食和自由活动的影响。采用高脂饲料诱导建立肥胖大鼠模型,分别在肥胖和正常大鼠第四脑室注射不同剂量orexin-A或SB334867,观察光照和黑暗环境下两种大鼠0~4 h摄食量及活动量的变化。结果显示,第四脑室注射不同剂量orexin-A,光照条件下,正常和肥胖大鼠0~4 h摄食量和活动量均较生理盐水对照组明显增加,呈剂量依赖关系(P0.05~0.01);且肥胖大鼠摄食量和活动量显著高于正常大鼠;黑暗条件下,不同剂量的orexin-A对正常和肥胖大鼠摄食量和活动量均没有明显改变(P0.05)。第四脑室注射不同剂量SB334867,光照条件下,正常和肥胖大鼠0~2 h,2~4 h摄食量和活动量均较生理盐水对照组明显减少(P0.05);且肥胖大鼠摄食量和活动量均显著高于正常大鼠;黑暗条件下,正常和肥胖大鼠摄食量和活动量均没有明显改变(P0.05)。以上结果提示,第四脑室周核团可能是orexin-A及OX1R作用靶点之一;光照条件对orexin-A和OX1R生理功能的发挥可能具有重要影响。     

下丘脑LHA-VMH Ghrelin信号通路对肥胖大鼠摄食选择、胃肠道运动及自发活动的影响及机制研究

目的:探究下丘脑外侧区(LHA)-腹内侧核(VMH)ghrelin信号通路对肥胖大鼠的摄食选择、胃肠道运动及自发活动的影响。方法:采用免疫组织化学方法检测大鼠LHA中ghrelin受体的表达;观察LHA注射ghrelin对大鼠摄食选择胃肠道运动及自发活动的影响;电损毁VMH,观察LHA注射ghrelin对大鼠摄食的影响。结果:免疫组化结果显示,大鼠下丘脑LHA中存在ghrelin受体,且LHA-VMH之间存在纤维投射;大鼠LHA微量注射ghrelin后,肥胖(DIO)大鼠及肥胖抵抗(DR)大鼠的正常饮食、高脂饮食及高糖饮食均高于正常大鼠,但预注射ghrelin受体拮抗剂[D-Lys3]-GHRP-6 (DLS)能够阻断这种作用;而电损毁大鼠VMH,显著减弱了ghrelin对正常大鼠、DIO大鼠及DR大鼠的促摄食作用。大鼠LHA微量注射ghrelin后,正常大鼠、DIO大鼠及DR大鼠的自发活动中,X轴、Y轴方向上的活动增加,且总活动增加,但Z轴方向上活动无明显改变;此外,LHA注射ghrelin,DIO大鼠及DR大鼠的胃肠道转运速率明显加快,且DR大鼠胃肠道转运速率增加更为明显,而预注射ghrelin受体拮抗剂[D-Lys3]-GHRP-6(DLS)显著阻断ghrelin的促胃肠道转运作用。结论:下丘脑LHA-VMH ghrelin信号通路参与调节正常大鼠、DIO及DR大鼠的摄食选择、胃肠道运动及自发活动。     

灯盏花注射液抗新生鼠缺氧缺血性脑损伤的作用及对Bcl-2、Bax蛋白表达的影响

目的：观察灯盏花注射液对新生大鼠缺氧缺血脑损伤（HIBD）的保护作用及对Bcl-2、Bax蛋白表达的影响。方法：采用新生7日龄SD大鼠缺氧缺血性脑损伤模型,设立假手术组、缺氧缺血脑损伤模型组、灯盏花注射液治疗大、中、小剂量组、无菌注射用水对照组。采用硫堇染色、免疫组织化学染色的方法测定各组大鼠海马CA1区神经元密度、组织学分级及凋亡相关基因Bcl-2、Bax蛋白表达情况,并计数各时间点Bcl-2、Bax免疫阳性细胞数目及测定积分光密度值。结果：假手术组,大鼠海马CA1区无锥体细胞缺失,未见明显免疫阳性细胞。与假手术组比较,缺氧缺血脑损伤模型组、无菌注射用水对照组Bcl-2、Bax蛋白表达均于3 d时达到高峰（与其余各时间点比较差别有显著意义P〈0.05）,神经元密度明显降低,组织学分级显著增高,积分光密度值增加。灯盏花治疗组,与无菌注射用水对照组比较,Bcl-2蛋白表达进一步增加,积分光密度值增加;而Bax蛋白表达则减少,积分光密度值降低;神经元密度显著高于对照组,组织学分级明显降低。结论：灯盏花注射液可能是通过上调Bcl-2表达,抑制Bax表达,减轻缺氧缺血引起的神经元凋亡及迟发性神经元死亡。     

慢性复合应激增强大鼠空间学习和记忆能力

本文观察了慢性复合应激对大鼠学习与记忆功能的影响。实验采用成年 Wistar 大鼠, 将其随机分成应激组和对照组。采用垂直旋转、睡眠剥夺、噪音刺激和夜间光照4 种应激原, 无规律地交替刺激动物 6 周, 每天6 h, 制作慢性复合应激动物模型。采用 Morris 水迷宫和 Y- 迷宫测试大鼠学习与记忆成绩,并用 Cresyl violet 染色法对大鼠海马结构进行神经细胞计数。结果显示,应激组动物慢性复合应激后, 在 Morris 水迷宫内寻找隐蔽平台所需的时间(潜伏期)比对照组的明显地短(P<0.05), 表明应激鼠的空间记忆能力明显强于对照鼠;在 Y- 迷宫内寻找安全区的正确率比对照组的明显地高(P<0.05), 表明应激鼠的明暗分辨学习能力明显强于对照鼠; 应激鼠慢性复合应激后, 其海马结构齿状回、CA3 和CA1 区神经细胞密度极明显地高于对照鼠(P<0.001)。这些结果提示, 慢性复合应激可增强大鼠空间记忆能力和明暗分辨学习能力。本文并对慢性复合应激模式增强大鼠学习和记忆能力的可能原因进行了讨论。     

大鼠慢性多重应激模型的建立

目的:建立大鼠慢性多重应激模型,为研究应激性疾病提供实验模型.方法:健康雄性SD大鼠随机分为模型组(n=10)和对照组(n=10).模型组采用脉冲随机变动的噪声、夜间光照、足底电击以及强迫游泳和束缚的复合刺激为应激源,对大鼠实施刺激,观察行为变化,检测心率、血压、体重增长速率、食物利用率,测定血清ACTH和皮质酮并进行分析.结果:慢性多重应激大鼠由实验之初的兴奋状态逐渐进入抑制状态,血压心率上升,体重增长缓慢,食物利用率降低,血清ACTH和皮质酮增高.结论:慢性多重应激大鼠一般行为、基本生理体征和下丘脑-垂体-肾上腺轴(HPA)功能发生改变,应激反应处于持续亢奋状态,该模型是较稳定较理想的应激模型.     

Antiepileptic effects of ghrelin on pentylenetetrazole-induced seizures in rats

It is well known that neuropeptide Y (NPY) and gamma-aminobutyric acid (GABA) exert antiepileptic effects in animal models. It has recently been shown that ghrelin neurons increase the activities of GABA and NPY in the brain. Therefore it can be said that ghrelin is an antiepileptic agent. In this study we aimed to investigate the antiepileptic effect of ghrelin in an acute experimental epilepsy model in pentylenetetrazole (PTZ) injected rats. Adult male Wistar albino rats were divided into a control group and four experimental groups with seven rats in each group. In order to generate epileptic seizures, PTZ (50mg/kg) was injected intraperitoneally. The experimental groups received intraperitoneal injections of ghrelin at doses of 20, 40, 60 and 80microg/kg 30min before PTZ injection. After PTZ injection, the latencies were separated into three components: first myoclonic jerk, generalized clonic seizures and tonic generalized extension. The injection of 50mg/kg PTZ-induced epileptic seizures in the control group. The onset times of the three characteristic behavioral changes were significantly delayed and the duration of tonic generalized extension was diminished by dose-dependent ghrelin administration. Our results demonstrated that ghrelin suppresses the onset time of PTZ-induced seizures. In the light of our current knowledge, it seems that ghrelin may be considered as an antiepileptic drug.     

Urinary 8-OHdG elevations in a partial lesion rat model of Parkinson's disease correlate with behavioral symptoms and nigrostriatal dopaminergic depletion

Increased oxidative stress contributes to pathogenesis of Parkinson's disease (PD). 8-hydroxy-2'-deoxyguanosine (8-OHdG) is the oxidation product most frequently measured as an indicator of oxidative DNA damage. Several studies have shown increased 8-OHdG in PD patients. There are few basic laboratory data examining 8-OHdG levels in animal models of PD. In this study, we utilized hemiparkinsonian model of rats induced by intrastriatal injection of 6-hydroxydopamine (6-OHDA). The urinary 8-OHdG level was measured in relation to behavioral and pathological deficits arising from 6-OHDA-induced neurotoxic effects on the nigrostriatal dopaminergic pathway. All rats were subjected to a series of behavioral tests for 42 days after 6-OHDA injection. We collected urine samples with subsequent measurement of 8-OHdG level using ELISA kits. For immunohistochemical evaluation, tyrosine hydroxylase (TH) staining was performed. Significant increments in urinary 8-OHdG level were observed continuously from day 7 until day 35 compared to control group, which showed a trend of elevation as early as day 3. Such elevated urinary 8-OHdG level significantly correlated with all of the behavioral deficits measured here, suggesting that urinary 8-OHdG level provides a good index of severity of parkinsonism. Urinary 8-OHdG level also had a significant positive correlation with the survival rate of dopaminergic fibers or neurons, advancing the concept that oxidative stress during the early phase of 6-OHDA neurotoxicity may correspond to disease progression closely approximating neuronal degeneration in the nigrostriatal dopaminergic system. The present results demonstrate that alterations in urinary 8-OHdG level closely approximate onset and disease progression in PD.     

Reduced Motivation in the BACHD Rat Model of Huntington Disease Is Dependent on the Choice of Food Deprivation Strategy

Huntington disease (HD) is an inherited neurodegenerative disease characterized by motor, cognitive, psychiatric and metabolic symptoms. Animal models of HD show phenotypes that can be divided into similar categories, with the metabolic phenotype of certain models being characterized by obesity. Although interesting in terms of modeling metabolic symptoms of HD, the obesity phenotype can be problematic as it might confound the results of certain behavioral tests. This concerns the assessment of cognitive function in particular, as tests for such phenotypes are often based on food depriving the animals and having them perform tasks for food rewards. The BACHD rat is a recently established animal model of HD, and in order to ensure that behavioral characterization of these rats is done in a reliable way, a basic understanding of their physiology is needed. Here, we show that BACHD rats are obese and suffer from discrete developmental deficits. When assessing the motivation to lever push for a food reward, BACHD rats were found to be less motivated than wild type rats, although this phenotype was dependent on the food deprivation strategy. Specifically, the phenotype was present when rats of both genotypes were deprived to 85% of their respective free-feeding body weight, but not when deprivation levels were adjusted in order to match the rats'' apparent hunger levels. The study emphasizes the importance of considering metabolic abnormalities as a confounding factor when performing behavioral characterization of HD animal models.     

Effect of physical training on basal metabolism. (1). Aging and long-term exercise loaded at a moderate intensity in rats

Effect of training on basal metabolism in rats by means of long-term exercise loaded at a moderate intensity were studied. The Wistar-strain male rats were carefully bred at the room temperature of 23.0 +/- 1 degree C and humidity of 60%. The first physical training was carried out by motor driven treadmill for 8 weeks at a speed of 25 m/min for less than 15 min once daily and 6 times in a week after 4 weeks of birth. Continuously, the second training was carried out for 15 months at the same load of one time per week. Running ability and the recovery of glycogen in exhausted skeletal muscles on period of the first training, loaded from 4 weeks to 12 weeks after birth. There was no change on the basal metabolism between the trained and sedentary control rats. In general, the basal metabolism significantly fell by aging, for instance, 24 months rat's basal metabolism was 63% of 3-4 months rat's. The second training repressed a decline of running ability and rose the recovery of muscle glycogen in rats, though training could not be stopped lowering of basal metabolism in aged rats.     

两种非甾体类解热镇痛剂对清醒状态血管源性头痛模型大鼠的行为学影响

目的电刺激大鼠上矢状窦硬脑膜建立血管源性头痛清醒动物模型,观察经典止痛药物乙酰氨基酚及布洛芬对清醒大鼠的行为学变化,验证此模型的可靠性。方法 30只雄性SD大鼠随机分为对照组（生理盐水组）、对乙酰氨基酚组、布洛芬组,每组给药前及给药后40 min分别给予5 min持续电刺激,观察清醒状态下大鼠用药前后行为学变化,主要观察的行为学指标为甩头次数和过度理毛时间。结果对照组与对乙酰氨基酚组以及对照组与布洛芬组甩头次及理毛时间均减少,差异均具有统计学意义（P〈0.05）,对乙酰氨基酚组及布洛芬组对模型动物行为学影响的差异无显著统计学意义。结论对乙酰氨基酚和布洛芬明显改善模型动物的头痛症状。清醒状态下大鼠上矢状窦硬脑膜电刺激的头痛模型切实可靠。     

心理应激对大鼠旷场行为的影响及酪氨酸干预作用研究

目的：观察心理应激对大鼠自主探究行为的影响,并探讨酪氨酸干预对心理应激动物的作用。方法：将Wistar大鼠随机分为5组（n=10）：正常对照组、应激对照组和低、中、高剂量酪氨酸补充应激组。测定动物的旷场行为表现,以放免法检测血浆皮质醇水平,以化学荧光法检测血浆去甲肾上腺素和多巴胺含量。结果：束缚应激使动物的血浆皮质醇水平明显升高,并出现体重增长缓慢。与正常对照组相比,应激对照组动物在旷场中的潜伏期延长、水平运动和垂直运动次数减少,而中剂量酪氨酸补充应激组和高剂量酪氨酸补充应激组动物的旷场行为表现未见显著差异。应激对照组和低剂量酪氨酸补充应激组动物的血浆去甲肾上腺素和多巴胺水平降低,其它动物未见明显变化。结论：应激引起动物应激激素分泌增加,旷场行为表现异常,而补充酪氨酸可减轻应激造成的这种不良影响。其机制可能涉及神经递质去甲肾上腺素和多巴胺水平的变化。     

Reduction in neuronal L-type calcium channel activity in a double knock-in mouse model of Alzheimer's disease

Increased function of neuronal L-type voltage-sensitive Ca(2+) channels (L-VSCCs) is strongly linked to impaired memory and altered hippocampal synaptic plasticity in aged rats. However, no studies have directly assessed L-VSCC function in any of the common mouse models of Alzheimer's disease where neurologic deficits are typically more robust. Here, we used cell-attached patch-clamp recording techniques to measure L-VSCC activity in CA1 pyramidal neurons of partially dissociated hippocampal "zipper" slices prepared from 14-month-old wild-type mice and memory-impaired APP/PS1 double knock-in mice. Surprisingly, the functional channel density of L-VSCCs was significantly reduced in the APP/PS1 group. No differences in voltage dependency and unitary conductance of L-VSCCs were observed. The results suggest that mechanisms for Ca(2+) dysregulation can differ substantially between animal models of normal aging and models of pathological aging.     

Hippocampal Glutamate Level and Glutamate Aspartate Transporter (GLAST) are Up-Regulated in Senior Rat Associated with Isoflurane-Induced Spatial Learning/Memory Impairment

Postoperative cognitive decline is a clinical concern especially for senior patients. It is generally recognized that glutamatergic system plays a crucial role in the physiopathologic process of neurocognitive deterioration. However, alterations of glutamatergic system in prolonged isoflurane-induced learning/memory decline are still unclear. This study investigates the question whether glutamate concentration and corresponding transporters or receptors display any alternations in aged rat suffering from isoflurane-induced learning/memory impairment. 111 male Sprague–Dawley rats (>18 months) were randomly divided into two main groups: hippocampal microdialysis group (n = 38) and western blotting group (n = 73). Each group was subdivided into three subgroups including (1) control subgroup (n = 6 and 10, receiving no behavioral trial, anesthesia or air exposure); (2) air-exposed subgroup (n = 7 and 15, receiving behavioral trial and air exposure but not anesthesia); (3) isoflurane anesthesia subgroup (n = 25 and 48, receiving both behavioral trial and anesthesia). The isoflurane-exposed rats were further divided into a learning/memory-impaired subgroup and a non-learning/memory-impaired subgroup according to their behavioral performance, which was measured using Morris water maze. Hippocampal glutamate concentrations in microdialysates were determined by high-performance liquid chromatography. Expression levels of GLAST, GLT-1, NMDAR1, NMDAR2A/B, AMPAR and tau in hippocampus were assessed via quantitative Western blotting. The incidences of learning/memory impairment of isoflurane-exposed rats in hippocampal microdialysis group and western blotting group were 12.0 (3/25) and 10.4 % (5/48) respectively. The intra-anesthesia hippocampal glutamate levels were significantly lower than those of non-anesthesized rats. The learning/memory-impaired rats showed a long-lasting increased glutamate level from 24 h after isoflurane exposure to the end of the study, but the other 22 isoflurane-exposed rats did not. The learning/memory-impaired subgroup displayed a significantly higher GLAST level than the other three subgroups (p = 0.026, 0.02 and 0.032 respectively). The expression levels of GLT-1, NMDAR1, NMDAR2A/B and AMPAR of every subgroup were comparable. We found a continuous raised hippocampal glutamate and an up-regulation of GLAST rather than GLT-1, NMDAR1, NMDAR2A/B, AMPAR or tau in hippocampus of aged rats associated with isoflurane-induced learning/memory impairment.     

Tetrahydroxystilbene glucoside improves learning and (or) memory ability of aged rats and may be connected to the APP pathway

The aim of this study is to evaluate the protective effects of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) on learning and (or) memory deficit in aged rats, as well as to explore the possible connection between TSG and the β-amyloid precursor protein (APP) pathway. Sprague-Dawley rats were randomly divided into a young control group (age, 4?months), an aged control group (age, 22?months), and a TSG-treated group (age, 22?months). TSG at doses of 50?mg·kg(-1)·day(-1) was intragastrically administered to 22-month-old rats for 4?weeks. The learning and (or) memory ability was measured using the Morris water maze (MWM) test, and the mRNA and protein expression of APP pathway proteins was measured by real-time polymerase chain reaction (RT-PCR) and Western blot, respectively. The aged rats exhibited obvious learning and (or) memory deficit when compared with the young rats, but TSG treatment significantly improved the learning and (or) memory ability in the aged rats, as noted from the MWM test. RT-PCR and Western blot analysis showed an increase in the expression of beta-site APP cleaving enzyme 1 (BACE1) and A Disintegrin And Metalloproteinase 17 (ADAM17) in aged rats, and a decrease in ADAM10; however, TSG treatment significantly increased the mRNA and protein expression of ADAM10 (p?< 0.01, compared with aged control rats). These results provide solid evidence for the therapeutic effect of TSG on age-related cognitive impairment, especially spatial learning and memory deficit. TSG might exert this effect through the APP pathway, although further studies on the topic are required.