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22.
目的:探究Aβ低分子量寡聚体对大鼠学习记忆功能的影响;方法:双侧海马内一次性注射Aβ低分子量寡聚体,15天后开始进行行为测试,测试方法采用跳台实验法、穿梭实验法和Morris水迷宫法;结果:跳台实验结果显示,与对照组比较,Aβ组跳台潜伏期短,错误次数多,差异有统计学意义(P<0.05);穿梭实验结果显示,与对照组比较,Aβ组由明箱进入暗箱的潜伏期短,错误次数多,差异有统计学意义(P<0.05);水迷宫实验结果显示,与对照组比较,Aβ组潜伏期长,跨越原平台次数少,差异有统计学意义(P<0.01);结论:Aβ组大鼠学习记忆能力和空间分辨能力降低,Aβ低分子量寡聚体在大鼠体内表现出较强的毒性作用。 相似文献
23.
摘要 目的:探讨神经节苷脂钠对缺血性脑卒中小鼠空间学习记忆能力的影响。方法:缺血性脑卒中小鼠模型(n=42)随机分为三组-模型组、氟西汀组与神经节苷脂钠组,每组14只小鼠。氟西汀组、神经节苷脂钠组、对照组分别给予10 mg/kg氟西汀与10 mg/kg神经节苷脂钠、等剂量生理盐水腹腔注射,1次/d,持续28 d。结果:氟西汀组、神经节苷脂钠组给药第7 d、14 d、28 d的逃避潜伏期、改良神经损伤严重程度评分(Modified neurological severity score,mNSS)低于模型组(P<0.05),穿越平台次数高于模型组(P<0.05),神经节苷脂钠组与氟西汀组对比差异有统计学意义(P<0.05)。氟西汀组、神经节苷脂钠组给药第28 d的海马组织B淋巴细胞瘤-2基因(B-cell lymphoma-2,Bcl-2)蛋白相对表达水平高于模型组(P<0.05),BCL2-Associated X(Bax)蛋白相对表达水平、脑卒中相对面积低于模型组(P<0.05),神经节苷脂钠组与氟西汀组对比差异有统计学意义(P<0.05)。结论:神经节苷脂钠在缺血性脑卒中小鼠的应用能促进恢复空间学习记忆能力,缓解神经损伤,抑制海马组织神经元细胞的凋亡,降低脑卒中面积。 相似文献
24.
Preissler T Luft T Kapczinski F Quevedo J Schwartsmann G Roesler R 《Neurochemical research》2007,32(8):1381-1386
Increasing evidence indicates that the gastrin-releasing peptide receptor (GRPR) is implicated in regulating synaptic plasticity
and memory formation in the hippocampus and other brain areas. However, the molecular mechanisms underlying the memory-impairing
effects of GRPR antagonism have remained unclear. Here we report that basic fibroblast growth factor (bFGF/FGF-2) rescues
the memory impairment induced by GRPR antagonism in the rat dorsal hippocampus. The GRPR antagonist [D-Tpi6, Leu13 psi(CH2NH)-Leu14] bombesin (6–14) (RC-3095) at 1.0 μg impaired, whereas bFGF at 0.25 μg enhanced, 24 h retention of inhibitory avoidance (IA)
when infused immediately after training into the CA1 hippocampal area in male rats. Coinfusion with an otherwise ineffective
dose of bFGF blocked the memory-impairing effect of RC-3095. These findings suggest that the memory-impairing effects of GRPR
antagonists might be partially mediated by an inhibition in the function and/or expression of neuronal bFGF or diminished
activation of intracellular protein kinase pathways associated with bFGF signaling. 相似文献
25.
Pereira P Vinadé E Rodrigues L De David e Silva TL Ardenghi P da Silva Brum LF Gonçalves CA Izquierdo I 《Neurochemical research》2007,32(7):1150-1155
The participation of protein serine/threonine kinases in memory formation and retrieval is well established. In contrast,
relatively little is known on the role of protein tyrosine kinases (PTKs). Previous work showed that intra-hippocampal infusion
of the Src-PTK inhibitor radicicol inhibits memory acquisition, consolidation, and retrieval of one-trial step-down inhibitory avoidance
task. In this study, we investigated the possible interaction between levels of Src-PTK activity in hippocampus and memory acquisition, formation, and retrieval of this task. Radicicol (0.5 μg/ml) was infused
into the CA1 region of the hippocampus of rats trained in a one-trial step-down inhibitory avoidance task. Radicicol infused
15 min before training decreased Src-PTK activity, as measured 0, 1.5, and 24 h after training, and impaired memory acquisition of the task. When given immediately
after training, there was a decrease in Src-PTK activity 1.5 h, but not 0 or 24 h after training. This treatment depressed memory consolidation. Radicicol infused into
CA1 10 min prior to retrieval testing inhibited hippocampal Src-PTK activity, as measured immediately after the test session. The results suggest that Src-PTKs participate in memory acquisition, consolidation, and retrieval processes, but the timing of the role of the enzyme
is different in each case. 相似文献
26.
Substances such as acetylcholine and glutamate act as both neurotransmitters and neuromodulators. As neuromodulators, they
change neural information processing by regulating synaptic transmitter release, altering baseline membrane potential and
spiking activity, and modifying long-term synaptic plasticity. Slice physiology research has demonstrated that many neuromodulators
differentially modulate afferent, incoming information compared to intrinsic and recurrent processing in cortical structures
such as piriform cortex, neocortex, and the hippocampus. The enhancement of afferent (external) pathways versus the suppression
at recurrent (internal) pathways could cause cortical dynamics to switch between a predominant influence of external stimulation
to a predominant influence of internal recall. Modulation of afferent versus intrinsic processing could contribute to the
role of neuromodulators in regulating attention, learning, and memory effects in behavior. 相似文献
27.
Ruizhi Wang Hongjie Wang Ivan Carrera Shaohua Xu Madepalli K. Lakshmana 《The Journal of biological chemistry》2015,290(14):9299-9309
Brain accumulation of neurotoxic amyloid β (Aβ) peptide because of increased processing of amyloid precursor protein (APP), resulting in loss of synapses and neurodegeneration, is central to the pathogenesis of Alzheimer disease (AD). Therefore, the identification of molecules that regulate Aβ generation and those that cause synaptic damage is crucial for future therapeutic approaches for AD. We demonstrated previously that COPS5 regulates Aβ generation in neuronal cell lines in a RanBP9-dependent manner. Consistent with the data from cell lines, even by 6 months, COPS5 overexpression in APΔE9 mice (APΔE9/COPS5-Tg) significantly increased Aβ40 levels by 32% (p < 0.01) in the cortex and by 28% (p < 0.01) in the hippocampus, whereas the increases for Aβ42 were 37% (p < 0.05) and 34% (p < 0.05), respectively. By 12 months, the increase was even more robust. Aβ40 levels increased by 63% (p < 0.001) in the cortex and by 65% (p < 0.001) in the hippocampus. Similarly, Aβ42 levels were increased by 69% (p < 0.001) in the cortex and by 71% (p < 0.011) in the hippocampus. Increased Aβ levels were translated into an increased amyloid plaque burden both in the cortex (54%, p < 0.01) and hippocampus (64%, p < 0.01). Interestingly, COPS5 overexpression increased RanBP9 levels in the brain, which, in turn, led to increased amyloidogenic processing of APP, as reflected by increased levels of sAPPβ and decreased levels of sAPPα. Furthermore, COPS5 overexpression reduced spinophilin in both the cortex (19%, p < 0.05) and the hippocampus (20%, p < 0.05), leading to significant deficits in learning and memory skills. Therefore, like RanBP9, COPS5 also plays a pivotal role in amyloid pathology in vivo. 相似文献
28.
29.
V.R. CoelhoJ. Gianesini R. Von BorowskiL. Mazzardo-Martins D.F. MartinsJ.N. Picada A.R.S. SantosL.F.S. Brum P. Pereira 《Phytomedicine》2011,18(10):896-901
It is known that (−)-linalool is a competitive antagonist of NMDA receptors, which play a key role in the learning and memory processes; however, only a few studies have reported a possible interference of (−)-linalool in memory. The purpose of this study was to investigate the (−)-linalool effects on acquisition of short- and long-term memories through the objects recognition task, inhibitory avoidance test and habituation to a novel environment. Furthermore, the open field test was used to investigate the interference of (−)-linalool in motivation, locomotion and exploration by animals. Wistar male adult rats received an intraperitoneal injection (i.p.) of saline (NaCl 0.9%), tween 5% or (−)-linalool (50 or 100 mg/kg) before training in the tasks; MK-801 (0.1 mg/kg), a glutamate antagonist, was used as positive control. Short-term (STM) and long-term (LTM) memories were tested 1.5 and 24 h after training, respectively, in the inhibitory avoidance and recognition objects. The results suggested that (−)-linalool (as 50- and 100-mg/kg doses) impaired LTM acquisition, but not STM acquisition, in the object recognition task. In the inhibitory avoidance test, animals receiving linalool (both doses) showed impairment in acquisition of both memories measured. In the open field test, the animals that received (−)-linalool showed no significant difference in the crossings and latency to start the locomotion in any of the doses tested, although (−)-linalool 100 mg/kg reduced rearing behavior. When re-exposed to open field 24 h after training, the rats that received (−)-linalool 100 mg/kg showed no habituation. Taken together, these data suggested that (−)-linalool was able to impair the acquisition of memory in rats, which can be associated to (−)-linalool antagonist capacity as regards NMDA glutamatergic receptors, since other glutamate antagonists also seem to affect memory. 相似文献
30.
Park CM Choi JI Choi JH Kim SY Park WK Seong CM 《Bioorganic & medicinal chemistry letters》2011,21(2):698-703
Piperazinyl derivatives of 1-(arylsulfonyl)-2,3-dihydro-1H-quinolin-4-ones have been identified with high binding affinities for 5-HT6 receptor. In particular, 2-methyl-5-(N-methyl-piperazin-1-yl)-1-(naphthalene-2-sulfonyl)-2,3-dihydro-1H-quinolin-4-one (8g) exhibits high binding affinity toward 5-HT6 (IC50 = 8 nM) receptor with good selectivity over other serotonin and dopamine receptors. 相似文献