低氧预适应增强小鼠学习记忆能力

目的探讨脑低氧预适应对Balb／C小鼠学习记忆能力的影响，进一步研究低氧预适应的机制。方法选用清洁级成年健康雄性Balb／C交系小鼠，数字表法随机分为3组（n=12）：①对照组（H0）；②1次低氧组（H1）；③4次低氧组印低氧预适应组（H4）。然后行改良的Morris水迷宫测试：在一直径约为1米的圆形水槽边缘等距的四个点（NESW）处做好标记，在一固定位置放一玻璃平台，使槽中水面高于平台1．5厘米，水面覆以泡沫屑，小鼠在水迷宫中训练5日后，进行低氧预适应模型制备，随后分别在低氧处理后1小时、2小时、4小时、1天、2天、3天进行测试，共进行6个时段测试，每个时段4次，分别将小鼠从改良的Morris水迷宫的NESW4个起始点放入水槽中任其游动，寻找平台，记录每次的遗避潜伏期，将4次平均值作为该小鼠在该时段的成绩。然后比较各组测定的小鼠在迷宫中的逃避潜伏期，以确定低氧预适应对小鼠学习记忆能力的影响。结果H4组小鼠在低氧处理后4小时、1、2．3天的逃避潜伏期明显短于H0和H1组（P〈0．05）。结论脑低氧预适应能增强小鼠学习记忆能力，具体的产生机制需要进一步的研究。     

不同入肝血流阻断方式对小鼠肝癌生长和转移的影响

目的探讨不同血流阻断方式对肝癌生长和转移的影响。方法选择昆明小鼠24只,随机分为正常对照组(suspended operation,SO)、肝门阻断组(occlusion of the portal triad,OPT)、保留肝动脉持续阻断门静脉组(occlusion of portal vein,OPV)各8只。采用门静脉注射肿瘤的方法建立肝癌模型,建模后3d采用阻断范围为左外叶和中叶、阻断时间为60min的入肝血流阻断方式,复流后5d分别对三组动物测定肝脏置换区域(HRA)、增殖性细胞核抗原(PCNA)在肝癌组织中的阳性表达率。结果门静脉注射小鼠肝癌细胞8d后,对照组阻断叶HRA(%)值为7.658±2.552,OPT组升高到35.612±4.234,OPV组升高到9.02±3.006(P<0.01);对照组非阻断叶HRA(%)值为8.107±2.003,OPT组升高到8.698±3.021,OPV组升高到8.607±2.304(P<0.01)。对照组中阻断叶与非阻断叶肿瘤生长比率为1,OPT组值为2.82,OPV组值为1.1。对照组中肿瘤细胞PCNA阳性表达率为30%,OPT组为78%,OPV组为45%。结论保留肝动脉持续阻断门静脉可减缓肝癌的生长和转移。     

加味保安方对带瘤C57小鼠血液流变学的影响

目的探讨加味保安方对Lweis肺癌C57小鼠血液流变学的影响。方法将Lweis肺癌C57小鼠分为加味保安方大、小剂量组,西黄丸对照组和模型组,并设一未带瘤的正常组,观察各组给药后对小鼠血液流变学变化的影响。结果加味保安方大、小剂量及西黄丸均可降低抑制Lweis肺癌肺癌C57小鼠的血液黏稠度(P<0.05),且作用强于西黄丸组(P<0.05)。结论加味保安方能明显降低Lweis肺癌C57小鼠血液黏稠度。     

Transgenic expression of the protein-L-isoaspartyl methyltransferase (PIMT) gene in the brain rescues mice from the fatal epilepsy of PIMT deficiency

Protein-L-isoaspartyl methyltransfearase (PIMT) plays a physiological role in the repair of damaged proteins containing isoaspartyl residues. In previous studies, we showed that PIMT-deficient mice developed a fatal epileptic seizure associated with the accumulation of damaged proteins in the brain. The mutant mice also showed a neurodegenerative pathology in hippocampi and impaired spatial memory. Still undefined, however, is how the accumulation of isoaspartates leads to the death of PIMT-deficient mice. In the present study, we generated PIMT transgenic (Tg) mice to investigate whether the exogenous expression of PIMT could improve the symptoms associated with PIMT deficiency. Rescue experiments showed that Tg expression of PIMT driven by a prion promoter effectively cured the PIMT-deficient mice. Biochemically, a higher expression level of transgene led to the effective repair of damaged proteins in vivo. Although a lower level of expression caused an accumulation of damaged proteins in a partially rescued line, the mice survived. Interestingly, synapsin I, which was extensively modified posttranslationally in PIMT-deficient mice, was specifically repaired in a partially rescued, but symptom-improved, Tg line. Our results suggest that an overall accumulation of damaged proteins does not necessarily lead to a fatal epileptic seizure, whereas certain modifications, such as changes in synapsin I, may play a pivotal pathological role in epilepsy.     

Facilitated CA1 hippocampal synaptic plasticity in dystrophin‐deficient mice: Role for GABAA receptors?

Duchenne muscular dystrophy (DMD) is associated with cognitive deficits that may result from a deficiency in the brain isoform of the cytoskeletal membrane-associated protein, dystrophin. CA1 hippocampal short-term potentiation (STP) of synaptic transmission is increased in dystrophin-deficient mdx mice, which has been attributed to a facilitated activation of NMDA receptors. In this study, extracellular recordings in the hippocampal slice preparation were used first to determine the consequences of this alteration on short-term depression (STD). STD induction was facilitated in mdx as compared with wild-type mice in a control medium. Because brain dystrophin deficiency results in a decreased number of gamma-aminobutyric acid A (GABAA)-receptor clusters, we tested the hypothesis that neuronal disinhibition contributes to the enhanced synaptic plasticity in mdx mice. We found that the GABAA receptor antagonist, bicuculline, increased basal neurotransmission in wild-type, but not in mdx mice and prevented the enhanced STP and STD in the CA1 area of slices from mdx mice. The possibility that altered GABA mechanisms underlie the facilitation of NMDA receptor-dependent synaptic plasticity in mdx mice is discussed.     

In vitro H-serotonin (5-HT) synthesis and release in BALBc and C57BL mice. II. Cell body areas

"In vitro" 3H-5-HT and 3H-5-HIAA, newly synthesized from 3H-TRP, are measured in the brainstem, the anterior raphe nuclei and the locus coeruleus of C57BL and BALBc mice. As found for the caudate nucleus and the hippocampus, higher synthesis and release are determined in C57BL than in BALBc, for the locus coeruleus and more globally, for the brainstem. But these differences disappear when the study is carried on the raphe dorsalis and the raphe centralis nuclei. Therefore the serotonergic activity could be independently regulated at the level of cell bodies and at those of terminals. However, the 5-HT metabolism of NRD of BALBc mice could be submitted to a specific autoinhibition which could explain a lower 5-HT synthesis and release at the corresponding terminal level, compared to C57BL.     

胎盘多肽对肿瘤细胞生长抑制作用研究

目的　探讨胎盘多肽 (PPs)对小鼠肿瘤细胞体内、外生长的影响。方法　染料排斥试验及肿瘤细胞体内种植实验。结果　PPs在体外对肿瘤细胞无明显的直接杀伤作用 (P >0 0 5 ) ,但体内肿瘤种植实验中给药组H2 2 腹水瘤小鼠生命延长率为 70 % ,S180 实体瘤生长抑制率为 6 5 % ,与对照组相比实验组荷瘤小鼠生存时间有显著差异 (P <0 0 1 )且肿瘤的形成也有明显的抑制作用 (P <0 0 1 )。结论　PPs在体内有明显的抑瘤作用     

Genetic mapping of ASIC4 and contrasting phenotype to ASIC1a in modulating innate fear and anxiety

Although ASIC4 is a member of the acid‐sensing ion channel (ASIC) family, we have limited knowledge of its expression and physiological function in vivo. To trace the expression of this ion channel, we generated the ASIC4‐knockout/CreERT²‐knockin (Asic4^CreERT2) mouse line. After tamoxifen induction in the Asic4^CreERT2::CAG‐STOP^floxed‐Td‐tomato double transgenic mice, we mapped the expression of ASIC4 at the cellular level in the central nervous system (CNS). ASIC4 was expressed in many brain regions, including the olfactory bulb, cerebral cortex, striatum, hippocampus, amygdala, thalamus, hypothalamus, brain stem, cerebellum, spinal cord and pituitary gland. Colocalisation studies further revealed that ASIC4 was expressed mainly in three types of cells in the CNS: (i) calretinin (CR)‐positive and/or vasoactive intestine peptide (VIP)‐positive interneurons; (ii) neural/glial antigen 2 (NG2)‐positive glia, also known as oligodendrocyte precursor cells; and (iii) cerebellar granule cells. To probe the possible role of ASIC4, we hypothesised that ASIC4 could modulate the membrane expression of ASIC1a and thus ASIC1a signaling in vivo. We conducted behavioral phenotyping of Asic4^CreERT2 mice by screening many of the known behavioral phenotypes found in Asic1a knockouts and found ASIC4 not involved in shock‐evoked fear learning and memory, seizure termination or psychostimulant‐induced locomotion/rewarding effects. In contrast, ASIC4 might play an important role in modulating the innate fear response to predator odor and anxious state because ASIC4‐mutant mice showed increased freezing response to 2,4,5‐trimethylthiazoline and elevated anxiety‐like behavior in both the open‐field and elevated‐plus maze. ASIC4 may modulate fear and anxiety by counteracting ASIC1a activity in the brain.     

经鼻滴入海人藻酸引起C57BL/6小鼠嗅球和海马区神经元的退行性病变

目的 应用海人藻酸(KA)在C57BL／6小鼠建立神经退行性病变动物模型并观察其对嗅球神经元的影响。方法 经鼻滴人KA应用尼氏和嗜银染色观察海马及嗅球的病理变化，免疫组化检测Cyclooxygenase2(COX-2)的表达。结果 经鼻滴入KA成功地在C57BL／6小鼠建立了神经退行性病变动物模型，KA通过嗅神经引起双侧嗅球和海马损伤，其病变程度与小鼠体重和滴入KA剂量有关，同时KA引起了脑内明显的胶质细胞增生和炎症因子COX-2在嗅球部的表达。结论 经鼻滴入KA能够引起嗅球和海马的损伤。     

Systemic overexpression of the alpha 1B-adrenergic receptor in mice: an animal model of epilepsy

PURPOSE: A lack of selective alpha1-adrenergic receptor (alpha1-ARs) agonists and antagonists has made it difficult to clarify the precise function of these receptors in the CNS. We recently generated transgenic mice that overexpress either wild-type or a constitutively active mutant alpha 1B-AR in tissues that normally express the receptor. Both wild-type and mutant mice showed an age-progressive neurodegeneration with locomotor impairment and probable stress-induced motor events, which can be partially reversed by alpha 1-AR antagonists. We hypothesized that the wild-type and mutant mice may exhibit spontaneous epileptogenicity as compared with normal (nontransgenic) mice. METHODS: Normal, wild-type, and mutant mice were studied. Twenty mice (1 year old) underwent prolonged video-EEG monitoring over a 4-week period. Raw EEG data were blindly analyzed by visual inspection for the presence of interictal and ictal epileptic activities. RESULTS: During the acute postoperative period (< or = 3 days), both wild-type (26.1 +/- 8.07 spikes/day) and mutant mice (116.87 +/- 55.13) exhibited more frequent interictal spikes than did normal mice (2.17 +/- 0.75; p value, <0.05), but all three groups showed EEG and clinical seizures. During the later monitoring periods (>3 days), wild-type and mutant mice showed more frequent interictal spikes (15.44 +/- 4.07; p < 0.01; and 6.05 +/- 2.46; p < 0.05, respectively) as compared with normal mice (0.41 +/- 0.41), but only mutant mice had spontaneous clinical seizures (means +/- SEM). CONCLUSIONS: The selective overexpression of the alpha 1B-AR is associated with increased in vivo spontaneous interictal epileptogenicity and EEG/behavioral seizures. These results suggest a possible role (direct or indirect) for the alpha 1B-ARs in the development and expression of epileptogenicity.