Selective cytotoxic lesions of the retrohippocampal region produce a mild deficit in social recognition memory

Although a number of studies have implicated the hippocampal formation in social recognition memory in the rat, a recent study in this laboratory has demonstrated that selective cytotoxic lesions, confined to the hippocampus proper (encompassing the four CA subfields and the dentate gyrus), are without effect on this behaviour. This finding suggests that the hippocampus proper does not subserve social recognition memory in the rat, but does not preclude the possibility that other areas of the hippocampal formation, such as the entorhinal cortex or subiculum, could support this form of learning. The present study addressed this issue by examining the effects of selective cytotoxic retrohippocampal (RHR) lesions (including both the entorhinal cortex and subiculum) on social recognition memory in the rat. RHR lesions produced a mild social recognition memory impairment, although lesioned animals still displayed a reduction in investigation time between the first and second exposure to the juvenile. This result is consistent with other studies which have implicated the retrohippocampal or parahippocampal area in olfactory recognition memory processes. It also suggests, however, that other areas, out with the retrohippocampal region, are also likely to play an important role in social recognition memory.     

Pb2+ modulates the NMDA-receptor-channel complex

Summary The actions of Pb²⁺ on NMDA channel currents of acutely dissociated hippocampal CA1- and CA3-neurones from adult rats activated by aspartate plus glycine (asp/gly) were examined. A fast reversible and a slow irreversible response to Pb²⁺ were found. Pb²⁺ applied simultaneously with asp/gly decreased an inward current. The threshold concentration was below 2 M, the current was reduced > 90% at concentrations over 100 M, The decrease of the asp/gly activated current showed no voltage dependence. Opening of NMDA channels was not necessary for Pb²⁺-action, as preincubation in 50 M Pb²⁺-containing external solution for several seconds dramatically reduced the response to asp/gly/Pb²⁺. This effect was reversed within 2 to 5 s of wash. Presence of Pb²⁺ or asp/Pb²⁺ or glycine/Pb²⁺ in the external solution did not prevent recovery of the NMDA receptor/channel complex from desensitization. Prolonged perfusion of a cell with the asp/gly/Pb²⁺-containing external solution resulted in an irreversible decrease of the asp/gly current, whereas the amplitude of the asp/gly/Pb²⁺ response did not change over the duration of an experiment. We conclude that Pb²⁺ modulates NMDA channel activity via interaction with the NMDA/glycine receptor: as a result the channel current decreases.Abbreviations NMDA N-methyl-D-aspartate - LTP long-term potentiation - AP5 2-amino-5-phosphonovalerate - EGTA ethylene glycol bis(-aminoethylether)-N,N,N,N-tetraacetic acid - HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid Correspondence to H. L. Haas at the above address     

Altered mitochondrial oxidative phosphorylation in hippocampal slices of kainate-treated rats

Mitochondria provide the main neuronal energy supply and are important organelles for the sequestration of intracellular Ca2+. This indicates a possible important role for mitochondria in modulating neuronal excitability in normal function as well as in disease. Therefore, we have investigated mitochondrial oxidative phosphorylation in the kainate model of epilepsy. We measured the oxygen consumption of single 400-micron rat hippocampal slices applying high resolution respirometry and determined mitochondrial NAD(P)H autofluorescence signal changes in single slices by laser-excited fluorescence spectroscopy. We observed an about 2-fold higher (p<0.001) basal glucose oxidation rate in slices from kainate-treated animals. This increased endogenous energy consumption was found to be unrelated to spontaneous activity since it was not sensitive to the inhibitors of the sodium-potassium ATPase ouabain and of the mitochondrial adenine nucleotide translocator atractyloside. This finding suggested an increased mitochondrial energy turnover in kainate-induced epilepsy. Furthermore, the uncoupler-stimulated oxygen consumption of the slices was approximately 1.3-fold higher (p<0.01) in the kainate model. In accordance with the respirometric data, fluorescence spectroscopy showed decreased reduction levels of the mitochondrial NAD-system in glucose oxidizing slices from kainate-treated rats. The preincubation of epileptic hippocampal slices with either BAPTA AM, ruthenium red or TPP+ increased the atractyloside sensitivity of glucose oxidation to about 1.4-fold (p<0.01). These observations indicate that the increased mitochondrial energy turnover in hippocampal slices from kainate-treated rats is most possibly caused by futile Ca2+-cycling.     

Influence of the ventral hippocampal formation on plasma vasopressin, hypothalamic-pituitary-adrenal axis, and behavioral responses to novel acoustic stress

The ventral hippocampal formation (vHF) seems to constrain diverse responses to psychological stimuli, and disruption of this function may underlie severe neuropsychiatric diseases. In particular, the ventral subiculum inhibits hypothalamic-pituitary-adrenal axis (HPA) activity following psychological, but not systemic, stressors. Despite the difficulty in interpreting such HPA responses, they have been relied upon to further characterize vHF function, because increased HPA axis activity is implicated in neuropsychiatric disturbances, and reliance on behavioral and cognitive data is even more problematic. Plasma arginine vasopressin (pAVP), which is inhibited by psychological stimuli and is also implicated in diverse neuropsychiatric diseases, provides a less ambiguous measure of CNS function. To test if its inhibition by psychological stress is also mediated by the vHF, we conducted two studies. In the first, pAVP and behavioral responses to novel acoustic stress were assessed in rats with bilateral excitotoxic lesions of the ventral subiculum and the ventral hippocampus. The subiculum lesions blocked the fall in pAVP and enhanced escape behaviors, whereas the hippocampal lesions produced responses intermediate to those in the subiculum-lesioned and control rats. In the second study, the pAVP response was similarly blocked by small lesions restricted to those vHF subfields which project to the neuroendocrine hypothalamus, compared to the response in animals with lesions in other vHF subfields. These results indicate that discrete projections from the vHF inhibit the pAVP response to psychological stimuli, and suggest that pAVP may provide a reliable probe of vHF activity.     

铅对小鼠海马[Ca2+]的影响及L型钙通道的作用

目的　探讨铅对分离的小鼠海马细胞内游离钙的影响及其及L型钙通道的作用。方法　采用低浓度胰蛋白酶消化法分离小鼠海马细胞 ,并以莹光指标剂 (Fura 2 )作Ca2 荧光探针 ,用双波长荧光法测定海马细胞 [Ca2 ] i。结果　铅可致分离的小鼠海马细胞 [Ca2 ] i 升高 [由静息时的 (2 0 3 4± 10 86)nmol L升至 (4 2 3 3± 19 2 6)nmol L] ,而不论胞外是否有钙 ;铅可抑制钾诱发海马细胞 [Ca2 ] i 升高 ,尼莫地平可加强这种抑制作用 ,而BayK864 4则可部分消除这种抑制作用。结论　铅可致分离的小鼠海马细胞 [Ca2 ] i 升高作用与胞内钙库释放有关 ;铅的抑制钾诱发海马细胞 [Ca2 ] i 升高作用与其抑制L型钙通道有关。     

二甲亚砜对大鼠海马脑片谷氨酸毒性损伤的影响

目的　观察二甲亚砜 (DMSO)对大鼠海马脑片谷氨酸 (Glu)兴奋性毒性损伤的影响 ,以探讨其保护作用与剂量的关系。方法　在离体海马脑片灌流液中加入 Glu造成兴奋性毒性损伤 ,用电生理记录技术观察不同浓度的 DMSO对海马脑片顺向群峰电位 (OPS)的影响。结果　去除 Glu 1h后 ,DM-SO (0 .0 7mol/ L )组 OPS恢复幅度和恢复率分别为 (88.2± 2 2 .9) % ,83.3% ,与对照组相比差异有显著性意义 (P<0 .0 5 ) ,而且 DMSO组 OPS恢复幅度具有剂量依赖性。结论　 DMSO具有抗谷氨酸兴奋性神经毒性作用 ,且这一作用与所用剂量有关。     

喹硫平对脂多糖损伤后海马神经干细胞的保护作用

目的：探讨喹硫平（QUE）对脂多糖（LPS）损伤后海马神经干细胞（NSCs）活性的作用及增殖情况的影响,并初步研究胞外信号调节激酶（ERK ）信号通路在其中的作用。方法建立体外大鼠海马NSCs的LPS损伤细胞模型,分为对照组（Sham组）、LPS组、LPS＋ QUE组（包括0．5μmol／L、1μmol／L和2μmol／L三个不同剂量组）,作用48 h后,采用WST －8试剂检测细胞活性,蛋白质印迹（Western Blot）法检测磷酸化胞外信号调节激酶1／2（pERK1／2）的表达水平,5－溴脱氧尿嘧啶核苷（BrdU ）检测细胞增殖情况。并在培养基中添加ERK磷酸化抑制剂U0126,以进一步明确ERK信号通路在其中的作用。结果（1）细胞活力：与Sham组[吸光度值（0．371±0．027）]相比,LPS组（0．251±0．034）细胞活力显著下降（P ＜0．01）,而 LPS＋ QUE 1μmol／L 组（0．311±0．018）和 LPS＋ QUE 2μmol／L组（0．343±0．021）均显著抑制了LPS对其活力的影响（与LPS组相比,P＜0．05）。（2）West‐ern Blot结果显示,LPS组的pERK1／2表达水平（0．313±0．124）明显低于Sham组（1．417±0．141）及LPS＋QUE 1μmol／L组（0．681±0．098）组和LPS＋QUE 2μmol／L组（0．954±0．119）（P＜0．05）,而LPS组与LPS＋QUE 0．5μmol／L组（0．368±0．123）的pERK1／2表达水平接近。（3）BrdU 染色结果显示,LPS组的BrdU阳性细胞数百分比（23．098±2．153）％明显低于Sham组（40．388±2．910）％, LPS＋QUE 1μmol／L 组（28．742±1．536）％和 LPS＋ QUE 2μmol／L 组（31．369±2．313）％（P ＜0.05）。（4）U0126可抑制QUE（1μmol／L和2μmol／L）的上述作用。结论 QUE能抑制LPS导致的NSCs损伤,这种作用与调节ERK1／2的磷酸化有关。     

血管性痴呆小鼠海马神经元蛋白激酶C表达特征

目的观察血管性痴呆(VD)小鼠海马神经元蛋白激酶C(PKC)的变化特征。方法将3月龄雄性昆明小鼠60只随机分为假手术组、模型组。模型组采用双侧颈总动脉结扎、反复缺血再灌注法制备VD模型,假手术组仅暴露双侧颈总动脉但不结扎。术后第29天、30天,采用跳台实验和水迷宫实验测试2组小鼠行为学改变,并采用免疫组织化学法观察2组海马CA1区神经元PKC表达的变化。结果模型组小鼠在跳台实验和水迷宫实验中的学习、记忆成绩均低于假手术组,差异有统计学意义(P<0.05)。模型组小鼠PKC免疫反应阳性神经元平均光密度值(0.27±0.07),显著低于假手术组(0.32±0.06),差异有统计学意义(P<0.05)。结论VD小鼠海马神经元PKC表达减少,推测此现象参与了VD发病过程。