TRPV4-induced Neurofilament Injury Contributes to Memory Impairment after High Intensity and Low Frequency Noise Exposures

Objective Exposure to high intensity, low frequency noise(HI-LFN) causes vibroacoustic disease(VAD),with memory deficit as a primary non-auditory symptomatic effect of VAD. However, the underlying mechanism of the memory deficit is unknown. This study aimed to characterize potential mechanisms involving morphological changes of neurons and nerve fibers in the hippocampus, after exposure to HILFN.Methods Adult wild-type and transient receptor potential vanilloid subtype 4 knockout(TRPV4^-/-     

早期APP/PS1转基因阿尔茨海默病小鼠海马结构内有髓神经纤维改变的体视学研究

目的 探讨早期APP/PS1转基因阿尔茨海默病(Alzheimer's disease,AD)小鼠海马结构内有髓神经纤维及髓鞘的改变.方法 运用Morris水迷宫方法测试10月龄APP/PS1转基因AD小鼠和同月龄野生型小鼠的空间学习和记忆能力改变的情况;运用无偏体视学方法结合透射电子显微镜技术对各组小鼠海马结构总体积,CA1和齿状回(dentate gyrus,DG)内有髓神经纤维的总长度和总体积,以及有髓神经纤维髓鞘总体积进行三维定量研究.结果 ①与野生型小鼠相比,10月龄APP/PS1转基因AD小鼠的逃避潜伏期显著性增加(P＜0.05),所在象限游泳时间百分比显著减少(P＜0.01),而穿台次数差异无统计学意义(P＞0.05);②与野生型小鼠相比,10月龄APP/PS1转基因AD小鼠海马体积、CA1体积、DG体积均显著性减小(P ＜0.05,P＜0.01);③与同月龄野生型小鼠相比,10月龄APP/PS1转基因AD小鼠海马CA1区和DG内有髓神经纤维的总长度差异没有统计学意义(P＞0.05),但是海马CA1区和DG内有髓神经纤维的总体积显著性减小(P＜0.05),髓鞘总体积也显著减小(P ＜0.05,P＜0.01).结论 10月龄时APP/PS1转基因AD小鼠海马CA1和DG内均存在脱髓鞘改变,可能是引起AD早期空间学习记忆能力减退的结构基础之一.     

甘草次酸对雄黄致小鼠海马突触超微结构损伤的改善作用

目的：探讨甘草次酸（GA）对雄黄致小鼠海马突触超微结构损伤的改善作用,并阐明其相关机制。方法：60只ICR小鼠随机分为对照组[灌胃给予0.5%羧甲基纤维素钠（CMC-Na）水溶液]、雄黄组（灌胃给予雄黄混悬液1.35 g·kg^-1）和GA干预组（灌胃给予GA48 mg·kg^-1+雄黄1.35 g·kg^-1）（n=20）,每日1次,连续灌胃8周。采用新事物识别实验检测各组小鼠记忆能力和认知功能,测定各组小鼠海马组织中谷胱甘肽（GSH）水平,利用透射电镜观察海马CA1区突触超微结构、突触间隙宽度、突触活性带长度、突触后致密物（PSD）厚度和突触界面曲率等结构参数的变化。结果：与对照组比较,雄黄组小鼠新物体优先指数（PI）和海马组织中GSH水平明显降低（P<0.05）;与雄黄组比较,GA干预组小鼠新物体PI虽有所增大,但差异无统计学意义（P>0.05）,小鼠海马组织中GSH水平升高（P<0.01）。与对照组比较,雄黄组小鼠海马CA1区突触结构模糊,突触间隙宽度明显增加（P<0.01）,突触活性带长度变短（P<0.01）,PSD厚度明显变薄（P<0.01）,突触界面曲率减小（P<0.01）;与雄黄组比较,GA干预组小鼠海马CA1区突触结构较清晰、完整,突触间隙宽度变窄（P<0.05）,突触活性带长度变大（P<0.05）,PSD厚度增加（P<0.05）;突触界面曲率虽有所增大,但差异无统计学意义（P>0.05）。结论：雄黄可致小鼠海马突触结构参数改变,导致记忆能力和认知功能降低,GA可部分改善小鼠海马突触超微结构的异常变化。     

Effects of fluid percussion injury on the neuronal activity in the hippocampal CA1 area and the dentate gyrus of the rat

The effect of fluid percussion injury (FPI) on the propagation of neuronal activity in the rat hippocampus was investigated by using optical and extracellular recording techniques. Under anesthesia with pentobarbital sodium, a moderate impact (1.5-2.0 atm) was applied to the parietal cerebral cortex of the left hemisphere at -3 mm (i.e. caudal) from bregma, 3.5 mm lateral from the sagittal suture. Systemic oxygenation remained normal during the anesthesia. The rats recovered fully from anesthesia within 30-60 min, and their subsequent behavior, such as feeding and grooming, was normal. After a survival period of 1 week from the FPI or sham-operation, neuronal activities were recorded from the hippocampal CA1 region and the dentate gyrus (DG) in either coronal or horizontal brain slice preparations. In sham-operated rats, there was no significant difference in the neuronal activity between contralateral and ipsilateral hippocampal CA1 areas and DG. In coronal slices (-5.6(-)-6.4 mm from bregma), moderate impact (1.5-2.0 atm) markedly depressed the neuronal activity of the ipsilateral (impact side) CA1 region and of the DG directly under the cerebral cortex that received the impact. In horizontal slices, on the other hand, the neuronal activity was markedly enhanced in the ipsilateral hippocampal CA1 region and the DG adjacent the temporal lobe of the cerebral cortex. Field potentials were recorded from the dentate granule cell layer and the hippocampal CA1 pyramidal cell layer in either coronal or horizontal slice. Moderate impact strongly depressed the field potential in the ipsilateral CA1 region and DG directly under the injured cerebral cortex. In horizontal slices, the field potential was followed by multiple population spikes in ipsilateral hippocampal CA1 and the DG neurons. Bicuculline (15 microM) increased the number of spikes of the field potential even after the brain injury. These results suggest that FPI depresses the neuronal activity in the ipsilateral hippocampus directly under the injured parietal cortex, while it enhances the neuronal activity of the ipsilateral hippocampus adjacent to the temporal cortex. The facilitation of neuronal activity following FPI is not due to disinhibition resulting from depression of GABAergic interneuron activity.     

逍遥散对大鼠慢性束缚应激脑区NMDAR2A和NMDAR2B蛋白的调节作用

目的观察海马及杏仁核NMDAR2A和2B蛋白在束缚应激状态下蛋白表达变化及逍遥散的调节作用。方法采用每天捆绑3 h的方法制作慢性束缚应激动物模型,并用逍遥散进行干预,分别于7 d后和21 d后用Western blot方法检测各组大鼠海马CA1区、CA3区、齿状回（DG）和杏仁核的NMDAR2A和2B蛋白表达的情况。结果在分离的4个部位（CA1,CA3,DG和杏仁核）,发现NR2A和NR2B分子在其中都有表达。NR2A的表达：在CA3和DG区,7 d和21 d模型组的表达降低,差异具有统计学意义（P〈0.05和P〈0.01）,逍遥散组的表达升高,差异具有统计学意义（P〈0.05和P〈0.01）。NR2B的表达情况和NR2A基本一致。结论逍遥散对NR2A和NR2B有明显的调节作用,在海马的CA3和DG区最明显,对7 d和21 d的应激模型都有不同程度的改变作用,以维持机体原来的平衡状态。提示逍遥散对神经突触性的改变有生理性保护作用。     

L—型Ca^2＋通道在马桑内酯致痫中的作用

以马桑内酯大鼠癫痫样行为发作、脑电图改变和离体海马脑片CA1区锥体细胞痫样放电为指标，观察L-型电压依赖性Ca2 通过阻断剂硝苯吡啶对其致痫作用的影响。结果发现：实验组与对照组相比较，大鼠癫痫发作推迟，程度减轻，脑电痫波出现潜伏期延长，波幅下降。离体海马脑片CA1区锥体细胞痫样放电被抑制，EPSP降低（P＜0．05）。结果提示，马桑内酯可能通过激活L-型电压依赖性Ca2 通道，使神经细胞内游离Ca2 增多而致痫。     

红藻氨酸对海马CAl区突触传递的作用

OBJECTIVE: To investigate the effect of activated kainate receptor on both the excitatory and inhibitory synaptic transmission in the neurons in the hippocampal CA1 region. METHOD: Blind whole-cell voltage-clamp recordings were performed on the CA1 pyramidal cells in adult rat hippocampal slices to examine and analyze the effect of bath-applied kainate (10 micromol/L) on CA1 afferent fiber-evoked excitatory postsynaptic currents (EPSCs) and inhibitory postsynaptic currents (IPSCs), respectively. RESULTS: Activation of kainate receptor significantly depressed both IPSCs (P <0.01) and EPSCs (P <0.01) in neurons in the hippocampus CA1 region. CONCLUSION: Activation of kainate receptors directly inhibit excitatory and inhibitory input in those neurons, which contributes to the development of epilepsy in the hippocampus by affecting the dynamic balance of the hippocampal neurons.     

匹罗卡品致痫大鼠慢性期海马神经元突触重建的实验研究

目的 探讨颞叶癫痫海马的异常兴奋性与抑制性突触联系变化.方法 建立匹罗卡品致痫大鼠模型,在致痫后60 d左右,利用立体定位仪在活体内注射逆行性示踪剂荧光金(FG)至海马CAI、CA3区,免疫组化方法观察海马异常兴奋性突触联系,免疫荧光双标记法检测NPY中间神经元与FG的共表达,观察海马异常抑制性突触联系.结果 FG注人大鼠海马CA1区,实验组远离注射部位的CA1区、海马CA3区、下托可见FG标记的锥体细胞,实验组CA1区远离注射部位处、CA3区、门区均有FG标记的NPY中问神经元,对照组未见.FG注入大鼠海马CA3区,对照组及实验组CA3区全层、门区锥体细胞均可见大量FG标记,实验组中CA1区部分锥体细胞被FG标记,门区可见双标记的NPY中间神经元,对照组未见.结论 颞叶癫痫大鼠海马慢性期存在异常的兴奋性和抑制性回路重组,包括CAl区锥体细胞之间、下托-CA1区、CA1-CA3区异常的兴奋性联系,以及CA1区中间神经元之间、CA3-CA1区、门区-CA1区、门区-CA3区异常的抑制性神经网络.神经元网络的异常重组町能在颞叶癫痫慢性期的自发发作中起重要作用.

Abstract：

Objective To explore the aberrant formation of excitatory and inhibitory circuit rearrangements of hippoeampus in temporal lobe epilepsy.Methods Pilocarpine-induced animal model was established.At around Day 60 post-modeling,retrograde tracer fluorogold(FG)was injected in vivo into CA1 and CA3 areas of hippocampus by stereotaxic apparatus.Immunohistochemistry of FG was used to observe the aberrant excitatory circuit rearrangements.Double immunofluorescence with NPY(neuropeptide Y)and FG was performed to observe the aberrant inhibitory circuit rearrangements.Results After an iniection of FG into CA1 area.the FG-labeled pyramidal cells could be observed distantly from the zone of dye soread in CA1 area.CA3 area and subiculm.And the FG-labeled non-principal neurons could be seen in stratum oriens of CA1 and hilus in experimental group.Double immunofluorescence revealed that the FG-labeled NPY interneurons were located distantly from the zone of dye spread in CA1 area.CA3 area and hilus in experimental rats.When injection was administered in CA3 area.the FG-labeled pyramidal cells were visible in the whole CA3 area and hilus in both groups.Some pyramidal cells were present in CA1 in experimental group.Also some FG-labeled non-principle cells were foand in hilus and distantly from the zone of dve spread in CA1 area,And the FG-labeled NPY neurons could be seen in hilus in experimental rats.Conclusion Aberrant excitatory and inhibitory synaptic reconstruction exist in hippocampus in chronic phase of temporal lobe epilepsy,including excitatory synaptic connections among pyramidal cells in CA1 area.pyramidal cells between CAl and subiculum and pyramidal cells between CA1 and CA3,inhibitory synaptie connections among dendritie intemeurons in CA1 area,CA3 to CA1,hilus to CA1 and hilus to CA3area,These circuit arrangements may play an important role in the pathogenesis of epilepsy.     

去势后大鼠海马结构一氧化氮合酶阳性神经元的变化

目的：观察去势后大鼠海马结构一氧化氮合酶（NOS）阳性神经元的变化。方法：用黄递酶组织化学染色方法观察切除双侧卵巢后雌后SD大鼠海马结构NOS阳性神经元的形态，分布的变化，并进行计算机图像分析。结果：去势后海马结构NOS阳性神经元分布变化有区域差异性；NOS阳性神经元在下托、海马（CA）一区邻近下托的部分、CA三区、CA四区（CA4）和齿状回（DG）数目明显减少，而在CA二区数目明显明显增多，CA4和DG的NOS阳性神经元平均密度降低，胞体的平均周长和平均截面积都明显减少。结论：雌激素可能通过影响海马结构NOS的表达来影响学习和记忆。     

淫羊藿黄酮对转基因痴呆小鼠脑内突触相关蛋白的影响

目的 观察10月龄APP转基因模型小鼠脑内突触相关蛋白--突触素(SYP)及突触后致密物质-95(PSD-95)蛋白表达的改变,以及中药有效部位淫羊藿黄酮对转基因小鼠脑内SYP和PSD-95表达的影响.方法 用药组小鼠自4月龄开始灌胃给予淫羊藿黄酮小剂量(0.03g·kg-1·d-1)、大剂量(0.1 g·kg-1·d-1)6个月至10月龄,正常对照组、转基因阴性对照组及模型组以同样方式灌胃给予蒸馏水.应用免疫组化及Western印迹方法分别检测海马CA1区、CA3区、齿状回及皮质中SYP的表达以及海马CA1区及皮质中PSD-95的表达.结果 与转基因阴性对照组相比,10月龄APP转基因模型小鼠皮质SYP蛋白表达明显较低(降低率为51.3%,P＜0.01);海马CA1区、CA3区及齿状回SYP阳性细胞的IOD值明显较低(降低率分别为59.1%、57.7%及56.5%,均P＜0.01).皮质PSD-95蛋白表达明显降低(降低率为36.4%,P＜0.01);海马CA1区PSD-95阳性细胞数少于对照组(减少率为18.5%,P＜0.05).灌胃给药6个月后,淫羊藿黄酮小、大剂量组小鼠皮质SYP蛋白表达明显高于模型组(增加率分别为40.0%,P＜0.05和106.4%,P＜0.01);海马CA1、CA3区及齿状回SYP阳性细胞IOD值均明显增加(均P＜0.01).淫羊藿黄酮小、大剂量组小鼠皮质PSD-95蛋白表达明显增加(增加率分别为57.3%,P＜0.05和84.3%,P＜0.01).淫羊藿黄酮大剂量组小鼠海马CA1区PSD-95阳性细胞数明显增加(增加率为22.5%,P＜0.05).结论 淫羊藿黄酮能通过促进突触相关蛋白表达而发挥维护神经元突触正常结构的作用,提示淫羊藿黄酮对改善AD神经元突触损伤状况具有潜在应用价值.     

血管性痴呆大鼠认知障碍的NMDAR机制研究

目的：观察四血管阻断（4VO）大鼠海观NMDA受体NMDAR的变化规律，探讨其在血管性痴呆（VD）形成中的作用机制，方法：改良的Pulsinelli 4VO法建立大鼠血管性痴呆模型，电脑控制的穿梭箱系统和离体海马脑片诱导的CA1区LTP检测大鼠学习记忆，原位杂交方法检测大鼠海马NMDAR1 mRNA的表达。结果：VD组大鼠的主动回避反应在2周时较对照组显著下降（P＜0．05），4周和2月时更加明显（P＜0．01），海马脑片长时程增强（LTP）的诱导出现明显障碍；VD组2周时CA1和CA3区NMDAR1 mRNA表达较对照组增高，DG区无明显改变；4周和2月时海马各区表达均减低。结论：大鼠海马区NMDAR与学习记忆有关，在脑缺血的早期表达增高介导了兴奋毒性作用；但在,缺血后期，NMDAR mRNA表达减低可能与学习记忆损害有关，为进一步进行NMDAR拮抗剂和激动剂治疗VD的研究提供了实验依据。     

愈痫灵颗粒对戊四氮致痫大鼠海马CA3区超微结构及认知功能障碍的影响

目的探讨愈痫灵颗粒（YXL）对痫性大鼠海马CA3区超微结构及认知功能障碍的影响。方法采用腹腔注射戊四氮点燃癫痫大鼠模型,随机分为癫痫模型组、愈痫灵颗粒干预组、丙戊酸钠干预组、拉莫三嗪干预组、正常对照组共5组：跳台实验测试大鼠的学习记忆能力,透射电镜观察海马CA3区超微结构。结果造模后反应期和学习成绩比较。正常组与其它各组差异有统计学意义（P〈0．01）,潜伏期和记忆成绩比较,正常组与其它各组差异无统计学意义（P〉0．05）;抗痫药物干预后各组反应期和潜伏期及学习、记忆成绩比较差异有显著统计学意义（P〈0．001）,愈痫灵组与正常组比较差异无统计学意义（P〉0．05）,愈痫灵组、拉莫三嗪组优于丙戊酸钠组与模型组,差异有统计学意义（P〈0．05）;抗痫药物干预前后反应期、潜伏期、学习、记忆成绩比较,愈痫灵组、拉莫三嗪组差异有统计学意义（P〈0．01）,丙戊酸钠组、模型组差异无统计学意义（P〉0.05）,正常组反应期、潜伏期、记忆成绩差异无统计学意义（P〉0．05）,学习成绩差异有统计学意义（P〈0．01）。电镜观察模型组大鼠海马CA3区神经元可见明显损伤。愈痈灵组多数神经元结构正常。少数粗面内质网有轻度脱颗粒。结论愈痫灵颗粒减少戊四氮致痫大鼠海马组织神经元坏死可能是其改善癜痫大鼠认知功能障碍的作用机制之一。     

快速老化小鼠认知功能减退与海马 CA1区锥体细胞树突棘变化的相关性

目的：：探讨快速老化小鼠认知功能减退与海马 CA1区锥体细胞树突棘变化的关系。方法：选用6月龄雄性 SAM-P8和 SAM-R1小鼠各8只,分别作为实验组和对照组,通过 Morris 水迷宫实验检测小鼠认知状况,通过 Golgi 染色观察海马 CA1区树突棘的变化。结果：与 SAM-R1小鼠比较,SAM-P8小鼠逃避潜伏期明显延长,跨越平台次数明显减少,海马 CA1区树突棘密度明显减少,差异均具有统计学意义(P <0.01);Morris 水迷宫实验中第5天逃避潜伏期及跨越平台次数与海马 CA1区树突棘密度分别呈负、正相关(P <0.01)。结论：SAM-P8小鼠海马 CA1区树突棘密度的减少导致小鼠认知功能减退,可能与突触功能障碍和突触丢失相关。     

丹皮酚对血管性认知障碍小鼠认知功能的保护作用

目的：探讨丹皮酚对血管性认知障碍（VCI）小鼠认知功能及海马神经元损伤的影响。方法：雄性C57BL/6小鼠60只,随机分为假手术（Sham）组、模型（VCI）组、丹皮酚（Pae）低、中、高剂量治疗组,每组12只。采用双侧颈总动脉结扎（2VO）制备小鼠反复缺血再灌注VCI模型,Morris水迷宫检测小鼠的认知功能,尼氏染色观察小鼠海马神经元的形态学变化,比色法检测海马SOD活性、MDA和NO含量的变化。结果：VCI小鼠认知功能下降（P〈0.01）,海马CA1区神经元变性坏死,MDA和NO含量增加,SOD活性降低（P〈0.01）;丹皮酚中、高剂量治疗可显著提高VCI小鼠的学习记忆能力,减少VCI所致的海马CA1区神经元死亡,并降低MDA和NO含量,升高SOD活性（P〈0.05或P〈0.01）。结论：丹皮酚可有效增强VCI小鼠的认知功能,并改善海马神经元病理改变,可能与其抗氧化应激有关。     

大鼠颞叶癫痫点燃后海马NR2A mRNA、NR2B mRNA的时空表达变化

目的：探讨海马NMDA受体NR₂A、NR₂B亚单位的时空表达变与颞叶癫痫后脑损伤的关系。方法:将雄性Wistar大鼠随机分为3组，正常对照组5只，假手术组和海人酸(KA）致痫组各30只，采用KA杏仁核微量注射方法建立经典的大鼠颞叶癫痫点燃模型；假手术组和KA致痫组分别按点燃后6、24、72 h和7、14、21 d时间点分为6组，每组5只。采用原位杂交方法检测海马神经元NR₂A mRNA、NR₂B mRNA时程表达变化。结果：癫痫组海马各区NR₂A mRNA阳性细胞表达率均高于假手术组(P<0.05)，于点燃后21 d逐步恢复正常。NR₂B mRNA在癫痫组海马DG和CA₁区阳性细胞表达率总体上高于假手术组(P<0.05)，在CA3区与假手术组比较差异无显著性。回归分析显示NR₂A mRNA和NR₂B mRNA的阳性细胞表达率与颞叶癫痫存在明显的正相关关系（β=0.154，P=0.0001），NR₂B mRNA表达与颠叶癫痫的发生存在正相关关系(β=0.102，P=0.0001)。结论：颞叶癫痫大鼠海马NR₂A mRNA、NR₂B mRNA存在时空差异性表达改变可能与颞叶癫痫及其脑损伤过程有关。     

幼鼠反复癫痫发作致苔藓纤维发芽的动态变化及其与自发性发作的关系

目的 观察幼鼠反复癫痫发作致苔藓纤维发芽(MFS)的动态变化及其与慢性期反复自发性发作(SRS)的关系。方法 将190只幼年期Wistar大鼠随机分为4组：对照组(n=48)、EP1组(n=80)、空白组(n=12)和EP2组(n=50),应用氯化锂-匹罗卡品致痫幼鼠模型,诱导幼鼠在生后21、25、29d反复癫痫发作,采用Timm染色法观察EP1组幼鼠末次癫痫发作后1、3、7、14、20、30、45、60d海马MFS的动态变化;观察EP2组SRS情况,比较EP2组中出现SRS(EP2-SRS组)和未出现SRS(EP2-非SRS组)的大鼠MFS的差异;采用Nissl染色观察海马神经元坏死及凋亡情况,对CA3、CA1区神经元进行计数,观察SRS对海马神经元的影响。结果 Timm染色显示,与对照组相比,EP1组在反复癫痫发作后14d MFS明显增加,并持续至60d后(P<0.05),EP2-SRS组与EP2-非SRS组相比无明显差异(P<0.05)。EP2-SRS组与空白组相比,CA3、CA1区神经元损伤明显(P<0.05)。结论 幼年反复癫痫发作引起MFS明显增加;在氯化锂-匹罗卡品模型中,MFS可能不是导致SRS的因素。     

Selective deletion of dnmts in excitatory neurons impairs recognition memory and synaptic function in hippocampal network of adult mice

Objective: DNA methylation is one of the most important epigenetic modulation, which is catalyzed primarily by three methyltransferases, DNMT1, DNMT3a and DNMT3b. The aim of our study is to investigate the modulatory effect of DNMTs on hippocampus-dependent memory formation, and to explore the underlying molecular, cellular and synaptic mechanisms. Methods: Dnmt1, 3a and 3b were selectively deleted in the CA1 region of dorsal hippocampus by Cre/LoxP recombinase systerm, either with virus-mediated Cre expression in CA1 of Dnmtsflox/flox mice or conditional αCaMKII-Cre; Dnmtsflox/flox mice. Hippocampus-dependent and hippocampus-independent memory performance were evaluated in adult KO and control mice. RNA-seq analysis was conducted to screen differential expression genes in the hippocampus after conditional Dnmts knockout. Real-time qPCR and Western blot analysis were used to confirm the differential expression. We also analyzed the alteration in DNA methylation by Whole Genome Bisulfite Sequencing. Neuronal excitability, synaptic transmission and plasticity were measured in CA1 pyramidal neurons of hippocampal slices. Finally, we checked whether virus-mediated shRNA expression in hippocampal CA1 could ameliorate abnormal synaptic function and memory deficit observed in αCaMKII-Cre; Dnmstflox/flox mice. Results: We found that both Dnmt1flox/floxDnmt3aflox/flox mice and Dnmt3bflox/flox mice receiving AAV-Cre virus infection into CA1 region displayed recognition memory deficit to object place, but normal memory to novel object. All mice showed similar performance in fear memory tests. Also, virus infection and Dnmts deletion did not changed anxiety- or depression-like behavior. The object place recognition memory deficit was also observed in both αCaMKII-Cre; Dnmt1flox/floxDnmt3aflox/flox mice and αCaMKII-Cre; Dnmt3bflox/flox mice. The Cre expression in αCaMKII-Cre mice was verified to be dominant in hippocampal CA1. RNA-seq based gene expression and followed real-time qPCR and western blot analysis confirmed significant upregulation of certain genes after Dnmts deletion in aCaMKII-expression excitatory neurons in the hippocampus. WGBS analysis showed differentiated DNA methylation in related genes. Normal basal synaptic transmission but impaired LTP was observed in SC-CA1 path of both αCaMKII-Cre; Dnmt1flox/floxDnmt3aflox/flox mice and αCaMKII-Cre; Dnmt3bflox/flox mice. AAV-virus mediated specific shRNA expression in CA1 region of dorsal hippocampus interfered upregulation of candidate genes, rescued abnormal synaptic function, and ameliorated object place cognition impairment in both αCaMKII-Cre;Dnmt1flox/floxDnmt3aflox/flox mice and αCaMKII-Cre;Dnmt3bflox/flox mice. Virus-mediated shRNA expression in CA1 region of dorsal hippocampus did not affect recognition memory to novel object. Conclusion: In conclusion, our findings suggest that Dnmts in CA1 excitatory neurons plays an important role in regulating synaptic function and hippocampus-dependent recognition memory process by control the expression of certain target genes.     

内源性组胺对大鼠戊四唑点燃癫痫诱发记忆障碍的作用

目的：研究大鼠戊四唑点燃癫痫诱发记忆障碍的发病机制，并探讨内源性组胺对此类记忆障碍的作用。方法：大鼠隔日腹腔注射亚惊厥剂量（35mg／kg）的戊四唑，直至完全点燃。采用穿梭箱被动回避试验测定大鼠的记忆能力。化学荧光法测定脑内组胺含量。大鼠脑病理切片采用HE染色，在光学显微镜下计数海马完整神经元。结果：大鼠戊四唑点燃后记忆能力明显下降，表现为穿梭箱内被动回避反应潜时缩短，而腹腔内注射组胺前体物质组氨酸则阻断了被动回避反应潜时的缩短。戊四唑点燃后大鼠海马、丘脑和下丘脑组胺含量明显下降，同时点燃使海马CA1区和CA3区完整神经元数目分别减少至对照组的72．7％和78．9％。结论：戊四唑点燃癫痫可导致大鼠记忆能力下降，可能与癫痫造成的组胺能神经活性降低和海马神经元丢失有关。     

Zileuton对脑缺血后空间学习记忆障碍的改善作用

目的观察5-脂氧酶选择性抑制剂Zileuton对全脑缺血后空间学习记忆能力的改善作用。方法以两侧颈总动脉阻断合并低血压法诱导大鼠全脑缺血模型,Zileuton 30 mg/kg灌胃给药,共7天。应用Morris水迷宫实验检测大鼠空间学习记忆能力,海马切片观察CA1神经元病理变化。结果 Morris水迷宫实验表明,全脑缺血后大鼠活动总路径和逃避潜伏期明显延长,空间学习记忆能力下降（P〈0.05或P〈0.01）;Zileuton 30 mg/kg提高全脑缺血大鼠Morris水迷宫实验学习记忆成绩（P〈0.05）。海马病理切片观察显示,全脑缺血后海马CA1神经元损伤（P〈0.01）,Zileuton减轻脑缺血后神经元损伤（P〈0.05）。结论 5-脂氧酶抑制剂Zileuton能改善大鼠全脑缺血后空间学习记忆障碍,其机制与药物对海马CA1神经元的神经保护作用有关。     

P2X7受体在匹罗卡品致癫痫大鼠海马中的表达与分布

目的：探讨P2X7受体在匹罗卡品致癫痫大鼠海马中的动态表达与分布。方法：氯化锂-匹罗卡品诱导癫痫 持续状态大鼠模型,于癫痫发作后第1,3,7,14,28天取大鼠海马,Western印迹检测P2X7受体蛋白表达,免疫组织 化学分析P2X7受体在脑组织海马各区的分布。结果：大鼠腹腔注射匹罗卡品(33.9±12.3) min后出现双侧前肢阵挛伴后 肢站立。P2X7受体蛋白表达在癫痫发作后1 d开始上调,3 d后逐渐下降,第7天时表达达到最低,随后持续上调至 第28天,其中1,14,28 d时P2X7受体蛋白的表达水平与对照组相比,差异有统计学意义(P<0.05)。免疫组织化学结 果显示P2X7受体在海马各区均有分布,癫痫发作后在海马DG和CA3区表达趋势与蛋白表达一致,而在CA1区表达无 显著变化。结论：P2X7受体在癫痫持续状态大鼠中的表达变化呈时间依赖性和空间分布差异,P2X7可能参与慢性癫 痫发生。