电针对AD大鼠学习记忆能力及神经元凋亡的影响

目的:探讨电针对AD模型大鼠学习记忆能力和神经元凋亡的影响.方法:将40只健康SD大鼠随机分为正常组、假手术组、模型组和电针组,采用A1-40注入大鼠双侧Meynert核建立AD模型,电针组采用电针治疗,治疗一个月后用水迷宫试验测定各组大鼠学习记忆能力,然后处死大鼠检测海马及皮质的神经元凋亡百分比.结果:模型组出现学习记忆障碍,呈渐进性加重,4周时更为显著,而且在海马区和皮质区神经元有较高的凋亡比例,电针组有明显改善(P<0.01).结论:Meynert核注射A可使大鼠发生较持久的学习记忆功能障碍及胆碱能神经元凋亡,电针治疗可改善AD大鼠学习记忆能力,抑制神经元凋亡.     

额叶皮层损伤对大鼠基底前脑胆硷能神经元的影响

为探讨前额叶皮层局限性损伤对大鼠学习、记忆功能及基底前脑胆硷能神经元的影响。用外科手术造成大鼠 1侧前额叶皮层局限性损伤后不同时间 ,用Y型迷宫检测学习、记忆功能 ,用组织化学技术检测基底前脑含乙酰胆硷酯酶 (AchE)活性神经元。结果为前额叶皮层损伤后 1周 ,动物学习、记忆功能有所障碍 ,损伤同侧的基底前脑胆硷能神经元有所减少 ,但均无统计学意义。损伤后 2、3、4周 ,动物学习、记忆障碍明显 ,损伤同侧基底前脑胆硷能神经元明显减少 (P <0 .0 5) ,且两者变化相平行。结论为单侧前额叶皮质局限性损伤不仅可引起动物学习、记忆功能障碍 ,且可引起同侧基底前脑胆硷能神经元丢失 ,两者发展且相平行 ,提示基底前脑胆硷能神经元逆行性变性在动物额叶皮层损伤引起的学习、记忆障碍中起作用。     

电针对AD模型大鼠海马神经干细胞Nestin及学习记忆能力的影响

目的:探讨电针对淀粉样肽(-AP)所致阿尔茨海默病(AD)模型大鼠脑内Nestin表达的影响,并对其保护作用提供理论依据.方法:取健康的SD大鼠40只,随机分为正常组、假手术组、模型组和电针组.用A 1-40微量注射至大鼠双侧Meynert基底核,建立AD模型,用电针进行治疗.于治疗后用Morris水迷宫检测大鼠的学习记忆能力,用免疫组化染色法检测Nestin阳性神经细胞数的表达.结果:①学习记忆观察:电针组的逃避潜伏期较模型组明显缩短,大鼠在原平台象限游泳时间占整个游泳时间的百分比显著升高,穿过原平台所在位置的次数明显增加(<0.01).②Nestin免疫组化检测:电针组大鼠海马Nestin阳性神经元数量在治疗组表达最强,与模型组相比具有显著性差异(<0.01).结论:电针能增强AD模型大鼠海马神经干细胞Nestin的表达,提高AD大鼠的学习记忆能力,其机制尚需讨论.     

核桃仁提取物对AD模型大鼠海马和皮质区ChAT、AchE活性的影响

目的：观察核桃仁提取物对阿尔兹海默病(Alzheimer′s disease，AD)模型大鼠中枢胆碱能系统活性的影响，进而探讨核桃仁提取物对AD的防治作用.方法：采用双侧Meynert核立体定向注射微量Aβ1-40制造AD大鼠模型，分别使用核桃仁的3种提取物灌胃干预后，检测大鼠海马与皮质区胆碱乙酰转移酶(ChAT)、乙...     

bFGF对慢性应激小鼠学习记忆及海马Ach含量的影响

目的探讨碱性成纤维细胞生长因子(Basic fibroblast growth factor,bFGF)对慢性应激模型小鼠学习记忆的影响及海马内Ach含量的变化.方法利用不确定应激方法建立慢性应激动物模型,共4周;应激第15天开始每日应激前腹腔注射bFGF,持续15 d;应用跳台法和避暗法观察bFGF对慢性应激小鼠学习记忆的作用;碱羟胺比色法检测乙酰胆碱(Ach)含量.结果 bFGF组小鼠学习记忆能力提高,海马Ach含量增高.结论 bFGF通过增加海马内胆碱能功能,改善慢性应激小鼠学习记忆能力.     

神经元τ蛋白过度磷酸化时14-3-3ξ的变化

为探讨τ(tau)蛋白异常磷酸化时神经元内14-3-3e蛋白含量的变化,采用GF-109203X和wortmannin联合注射大鼠侧脑室,诱导大鼠海马神经元τ蛋白发生过度磷酸化,同时观察14-3-3e蛋白含量的改变,结果显示：GF-109203X和wortmannin诱导了海马CA3区神经元τ蛋白在Ser396/404位点的过度磷酸化,同时14-3-3ξ蛋白的含量显著增高,这些结果提示τ蛋白过度磷酸化与抗凋亡蛋白14-3-3之间可能的内在联系。     

胞二磷胆碱对大鼠脑缺血损伤后认知功能及海马神经元BCL-2,BAX表达和细胞凋亡的影响

探讨胞二磷胆碱对脑缺血损伤后大鼠认知功能和海马神经元BCL-2,BAX表达的影响.取健康Spra-gue-Dawley成年雄性大鼠60只,随机分为假手术对照组,缺血组和胞二磷胆碱组3组,每组20只.对缺血组和胞二磷胆碱组采用Zea Longa等法改良复制大脑中动脉狭窄(middle cerebral artery occlusion,MCAO)动物模型,通过Morris水迷宫系统观察各组大鼠学习记忆功能;免疫组化检测BCL-2,BAX表达,Tunel法检测神经元凋亡.胞二磷胆碱使Bcl-2蛋白表达从缺血对照组的39.88±5.41增加至55.13±8.17,BAX蛋白表达从缺血对照组的62.38±8.47下降至36.13±5.94,凋亡神经元从缺血对照组的18.67±3.86下降至14.67±4.25.胞二磷胆碱对脑缺血损伤后大鼠的神经保护作用可能是通过上调海马神经元Bcl-2蛋白、下调Bax蛋白的表达,减少海马神经元凋亡进而改善脑缺血损伤后大鼠的学习记忆能力.     

衰老大鼠学习行为与海马突触相关蛋白表达的研究

研究衰老大鼠的学习行为与海马内突触相关蛋白的表达．运用Y-迷宫方法对幼年对照组（断乳期）和老年期（22月龄）雄性Sprague—Dawley大鼠进行Y-迷宫空间学习记忆行为训练,之后利用免疫组化和Western blot方法检测2组大鼠海马内突触素（synaptophysin,Syn）、生长相关蛋白（GAP-43）的表达情况．研究结果：（1）2组相比,老年组的学习能力较强,幼年对照组记忆能力较强（P〈0．05）;（2）生长相关蛋白GAP-43在老年组海马内的表达显著高于幼年对照组;而突触素的表达低于幼年对照组（P〈0．01）．提示,GAP-43和突触素可能参与大鼠空间分辨学习记忆的过程,老年大鼠的中枢神经系统保持着潜在的神经元退化修复的功能．     

基底前脑胆碱能神经元损毁:一种老年性痴呆方法学动物模型的复制及应用要点

目的介绍一种老年性痴呆的方法学动物模型-基底前脑胆碱能神经元损毁模型的复制及应用要点,以及该模型比较生物学研究的有关进展。方法采用鹅膏覃氨酸基底前脑区Maynert基底核定位注射造模,通过水迷宫实验测试动物的学习记忆能力。结果该手术方法能造成动物学习记忆能力下降,但各组内动物个体差异极大,变异系数为27.1%~46.2%。以正常动物平均成绩的95%置信区间为标准,对造模的成功率进行筛选,表明该模型的成功率为50%~75%,说明了进行模型筛选的重要意义。结论基底前脑胆碱能神经元损毁模型对老年性痴呆研究具有重要价值,但在应用中需要注意有关方法学问题。     

鲨鱼肝蛋白粗提物对大鼠肝线粒体抗氧化功能的影响

摘以400mg／kg2次腹腔注射硫代乙酰胺（TAA）建立大鼠急性肝损伤模型,并在注射TAA前1h以80mg／kg2次腹腔注射鲨鱼肝蛋白粗提物进行预防,研究了鲨鱼肝蛋白粗提物对大鼠肝线粒体抗氧化功能的影响。注射TAA后,大鼠肝脏线粒体腺苷二磷酸（ADP）诱导的氧消耗、呼吸控制率（RCR）、磷／氧比（P／O）、氧化磷酸化率均低于对照组,而预防组线粒体ADP诱导的氧消耗、呼吸控制率、P／O和氧化磷酸化效率均高于模型组;TAA降低了线粒体中谷胱甘肽、谷胱甘肽还原酶、谷胱甘肽过氧化物酶的水平,而鲨鱼肝蛋白粗提物则使线粒体中谷胱甘肽过氧化物酶和超氧化物歧化酶的水平明显升高,说明鲨鱼肝蛋白粗提物能部分修复线粒体受损的呼吸功能,增强线粒体抗氧化能力。     

Spatial Memory Deficit and Tau Hyperphosphorylation Induced by Inhibiting PP2A in Rat Brain

Hyperphosphorylation of Tau in Alzheimer＇s disease （AD） brain appears to be caused by a down-regulation of protein phospbatase 2A （PP2A）. In this study, we selectively inhibited PP2A by injection of okadaic acid （OA） into the Meynert nucleus basalis of rats and found that 0.4 pmol of OA injeetion induced approximately 60% inhibition of PP2A 24 h after injection, 13% inhibition 48 h after injection and no obvious inhibition 72 h after injection. Hyperphosphorylation of Tau at Ser-198/ Ser-199/Ser-202 and Ser-396/Ser-404 and spatial memory deficit of rats were induced 24 h after 0. d prnol of OA injection. This study suggests that a dowreregulation of PP2A may underlie almormal hyperphosphorylation of cytoskeletal proteins leading to neurofibrillary degeneration in AD.     

Amelioration of cholinergic neuron atrophy and spatial memory impairment in aged rats by nerve growth factor

In aged rodents, impairments in learning and memory have been associated with an age-dependent decline in forebrain of cholinergic function, and recent evidence indicates that the cholinergic neurons in the nucleus basalis magnocellularis, the septal-diagonal band area and the striatum undergo age-dependent atrophy. Thus, as in Alzheimer-type dementia in man, degenerative changes in the forebrain cholinergic system may contribute to age-related cognitive impairments in rodents. The cause of these degenerative changes is not known. Recent studies have shown that the central cholinergic neurons in the septal-diagonal band area, nucleus basalis and striatum are sensitive to the neurotrophic protein nerve growth factor (NGF). In particular, intraventricular injections or infusions of NGF in young adult rats have been shown to prevent retrograde neuronal cell death and promote behavioural recovery after damage to the septo-hippocampal connections. It is so far not known, however, whether the atrophic cholinergic neurons in aged animals are responsive to NGF treatment. We report here that continuous intracerebral infusion of NGF over a period of four weeks can partly reverse the cholinergic cell body atrophy and improve retention of a spatial memory task in behaviourally impaired aged rats.     

Effects of the tumour promoter okadaic acid on intracellular protein phosphorylation and metabolism

Okadaic acid is a polyether derivative of 38-carbon fatty acid, and is implicated as the causative agent of diarrhetic shellfish poisoning. It is a potent tumour promoter that is not an activator of protein kinase C, but is a powerful inhibitor of protein phosphatases-1 and -2A (PP1 and PP2A) in vitro. We report here that okadaic acid rapidly stimulates protein phosphorylation in intact cells, and behaves like a specific protein phosphatase inhibitor in a variety of metabolic processes. Our results indicate that PP1 and PP2A are the dominant protein phosphatases acting on a wide range of phosphoproteins in vivo. We also find that okadaic acid mimics the effect of insulin on glucose transport in adipocytes, which suggests that this process is stimulated by a serine/threonine phosphorylation event.     

A synaptic memory trace for cortical receptive field plasticity

Receptive fields of sensory cortical neurons are plastic, changing in response to alterations of neural activity or sensory experience. In this way, cortical representations of the sensory environment can incorporate new information about the world, depending on the relevance or value of particular stimuli. Neuromodulation is required for cortical plasticity, but it is uncertain how subcortical neuromodulatory systems, such as the cholinergic nucleus basalis, interact with and refine cortical circuits. Here we determine the dynamics of synaptic receptive field plasticity in the adult primary auditory cortex (also known as AI) using in vivo whole-cell recording. Pairing sensory stimulation with nucleus basalis activation shifted the preferred stimuli of cortical neurons by inducing a rapid reduction of synaptic inhibition within seconds, which was followed by a large increase in excitation, both specific to the paired stimulus. Although nucleus basalis was stimulated only for a few minutes, reorganization of synaptic tuning curves progressed for hours thereafter: inhibition slowly increased in an activity-dependent manner to rebalance the persistent enhancement of excitation, leading to a retuned receptive field with new preference for the paired stimulus. This restricted period of disinhibition may be a fundamental mechanism for receptive field plasticity, and could serve as a memory trace for stimuli or episodes that have acquired new behavioural significance.     

Substance P raises neuronal membrane excitability by reducing inward rectification

Much interest has recently centred on the properties of peptides that modulate the excitability of nerve cells. Such compounds include the undecapeptide substance P, which is particularly well established as an excitatory neurotransmitter, and we examine here its effects on magnocellular cholinergic neurones taken from the medial and ventral aspects of the globus pallidus of newborn rats and grown in dissociated culture. These neurones have previously been shown to respond to substance P3 and are analogous to the nucleus basalis of Meynert in man, which gives a diffuse projection to the cerebral cortex and whose degeneration is the likely cause of Alzheimer's disease. Substance P depolarizes these cultured neurones by reducing an inwardly rectifying potassium conductances; this conductance has been found in several neuronal types and has similar properties to those of certain other cells. As discussed below, modulation of inward (or anomalous) rectification by substance P implies a self-reinforcing element to the depolarization caused by the peptide.     

A new area in the brain associated with learning and memory

A new subdivision, named marginal division (MrD)> consisting of spindle-shaped neurons, has been identified at the caudomedial margin of the neostriatum in the brains of the rat, cat, monkey and human. It is distinguishable from the rest of striatum by special neural connections and many intensely expressed neuropeptides and some monoamines in the fibers, terminals and neuronal somata. Three-dimensional reconstruction of the rat brain reveals that the MrD is a flat pan-shaped area between the neostriatum and globus pal-lidus. Chemical lesions of bilateral MrD in rats will result in severely impaired learning and memory functions, as was demonstrated by double blind Y-maze test. The function of MrD has been shown to be associated with learning and memory by functional magnetic resonance imaging (fMRl) technique in human brain in vivo . Functional neuronal connections are observed between the MrD and hippocampus, amygdala, as well as the basal nucleus of Meynert by chemically induced c-Fos immunohistochemical staining. MrD is a newly discovered part and a universal structure in the neostriatum of the mammalian brain. MrD might very possibly play an important role in processes of the learning and memory.     

核桃仁提取物对老年痴呆模型大鼠IL-1、IL-6含量影响的实验研究

目的:比较三种核桃仁提取物对老年痴呆模型大鼠脑内IL-1、IL-6含量影响。方法:采用Meynert基底核注射Aβ1-40建立老年痴呆模型,给予核桃仁水提取物、乙醇提取物、丙酮提取物进行连续灌胃治疗,并与正常空白组、假手术组及模型组对照。结果:模型组IL-1、IL-6含量显著高于正常空白组和假手术组(P<0.01),核桃仁水提取物、乙醇提取物、丙酮提取物均能显著降低其含量(P<0.01),而在降低IL-6含量时,以丙酮提取物效果最佳,3组提取物比较,P<0.05。结论:核桃仁提取物可以有效降低AD模型大鼠脑内炎因子IL-1、IL-6的含量,从而降低Aβ的毒性来防治AD,其中丙酮提取物效果最佳。