Exposure to intermittent hypoxia impairs learning and memory ability in rats

To study the effects of chronic intermittent hypoxia (CIH) on learning and memory ability in Sprague–Dawley rats, we established a rat model of CIH. A total of 24 male Sprague–Dawley rats were included and were assigned to three experimental groups (n = 8/group): the unhandled control (UC) group (normal feeding for 4 weeks), the CIH group (CIH for 4 weeks), and the removal of hypoxia (RH) group (normal feeding for 4 weeks after CIH for 4 weeks). All the results were analyzed using one-way ANOVA and comparison between groups was performed using S–N–K method. Performance on the Morris water maze test (a learning and memory test) was significantly worse for CIH rats than for UC rats and RH rats (P < 0.05), but was significantly better for RH rats than for UC rats (P < 0.05). Synaptophysin expression in the CA3 region of the hippocampus was reduced in the CIH group and the RH group compared with the UC group (P < 0.05), but was significantly greater in the RH group than in the CIH group (P < 0.05). Synaptophysin is a calcium-binding protein located in the membranes of presynaptic vesicles. Changes of synaptophysin expression may indirectly reflect the structural changes in the hippocampal CA3 region. In rats, CIH can cause declines in learning ability and memory and reduce the expression of synaptophysin in the CA3 region of the hippocampus; these effects could be partially rescued by the removal of hypoxic factors. The observed decline in learning and memory ability in rats may relate to a decrease in synapse quantity and structural changes in the CA3 region of the hippocampus.

     

Strigolactones' ability to regulate root development may be executed by induction of the ethylene pathway

The newly defined phytohormones strigolactones (SLs) were recently shown to act as regulators of root development. Their positive effect on root-hair (RH) elongation enabled examination of their cross talk with auxin and ethylene. Analysis of wild-type plants and hormone-signaling mutants combined with hormonal treatments suggested that SLs and ethylene regulate RH elongation via a common regulatory pathway, in which ethylene is epistatic to SLs. The SL and auxin hormonal pathways were suggested to converge for regulation of RH elongation; this convergence was suggested to be mediated via the ethylene pathway, and to include regulation of auxin transport.Key words: strigolactone, auxin, ethylene, root, root hair, lateral rootStrigolactones (SLs) are newly identified phytohormones that act as long-distance shoot-branching inhibitors (reviewed in ref. ¹). In Arabidopsis, SLs have been shown to be regulators of root development and architecture, by modulating primary root elongation and lateral root formation.^2,3 In addition, they were shown to have a positive effect on root-hair (RH) elongation.² All of these effects are mediated via the MAX2 F-box.^2,3In addition to SLs, two other plant hormones, auxin and ethylene, have been shown to affect root development, including lateral root formation and RH elongation.^4–6 Since all three phytohormones (SLs, auxin and ethylene) were shown to have a positive effect on RH elongation, we examined the epistatic relations between them by examining RH length.⁷ Our results led to the conclusion that SLs and ethylene are in the same pathway regulating RH elongation, where ethylene may be epistatic to SLs.⁷ Moreover, auxin signaling was shown to be needed to some extent for the RH response to SLs: the auxin-insensitive mutant tir1-1,⁸ was less sensitive to SLs than the wild type under low SL concentrations.⁷On the one hand, ethylene has been shown to induce the auxin response,^9–12 auxin synthesis in the root apex,^11,12 and acropetal and basipetal auxin transport in the root.^4,13 On the other, ethylene has been shown to be epistatic to SLs in the SL-induced RH-elongation response.⁷ Therefore, it might be that at least for RH elongation, SLs are in direct cross talk with ethylene, whereas the cross talk between SL and auxin pathways may converge through that of ethylene.⁷ The reduced response to SLs in tir1-1 may be derived from its reduced ethylene sensitivity;^7,14 this is in line with the notion of the ethylene pathway being a mediator in the cross talk between the SL and auxin pathways.The suggested ethylene-mediated convergence of auxin and SLs may be extended also to lateral root formation, and may involve regulation of auxin transport. In the root, SLs have been suggested to affect auxin efflux,^3,15 whereas ethylene has been shown to have a positive effect on auxin transport.^4,13 Hence, it might be that in the root, the SLs'' effect on auxin flux is mediated, at least in part, via the ethylene pathway. Ethylene''s ability to increase auxin transport in roots was associated with its negative effect on lateral root formation: ethylene was suggested to enhance polar IAA transport, leading to alterations in the quantity of auxin that unloads into the tissues to drive lateral root formation.⁴ Under conditions of sufficient phosphate, SL''s effect was similar to that of ethylene: SLs reduced the appearance of lateral roots; this was explained by their ability to change auxin flux.³ Taken together, one possibility is that the SLs'' ability to affect auxin flux and thereby lateral root formation in the roots is mediated by induction of ethylene synthesis.To conclude, root development may be regulated by a network of auxin, SL and ethylene cross talk.⁷ The possibility that similar networks exist elsewhere in the SLs'' regulation of plant development, including shoot architecture, cannot be excluded.     

老年学习记忆减退的神经行为学基础

用改良Ｍｏｒｒｉｓ水迷宫将老年大鼠分为老年学习记忆减退组和老年学习记忆正常组,并与青年组对照,检测其空间参考记忆和空间工作记忆,并对海马结构内胶质纤维酸性蛋白（ＧＦＡＰ）阳性胶质细胞和ＧＡＢＡ能中间神经元在光镜和电镜水平进行定量分析。结果显示老年学习记忆减退大鼠的空间参考记忆能力明显下降,并且其行为模式发生了改变,空间工作记忆改变不明显;齿状回分子层的病理改变非常明显,表现为ＧＡＢＡ能神经元丢失和     

Targeting amyloid-beta peptide (Abeta) oligomers by passive immunization with a conformation-selective monoclonal antibody improves learning and memory in Abeta precursor protein (APP) transgenic mice

Passive immunization of murine models of Alzheimer disease amyloidosis reduces amyloid-beta peptide (Abeta) levels and improves cognitive function. To specifically address the role of Abeta oligomers in learning and memory, we generated a novel monoclonal antibody, NAB61, that preferentially recognizes a conformational epitope present in dimeric, small oligomeric, and higher order Abeta structures but not full-length amyloid-beta precursor protein or C-terminal amyloid-beta precursor protein fragments. NAB61 also recognized a subset of brain Abeta deposits, preferentially mature senile plaques, and amyloid angiopathy. Using NAB61 as immunotherapy, we showed that aged Tg2576 transgenic mice treated with NAB61 displayed significant improvements in spatial learning and memory relative to control mice. These data implicated Abeta oligomers as a pathologic substrate for cognitive decline in Alzheimer disease.     

强制运动促进成年大鼠海马齿状回神经发生并提高学习能力

为了探讨强制运动对成年大鼠海马齿状回（dentate gyrus,DG）神经发生的影响,强制大鼠在马达驱动的转轮中跑步,用5-溴-2-脱氧尿苷（5-bromo-2-deoxyuridine,BrdU）标记增殖细胞,巢蛋白（neuroepthelial stem cell protein,nestin）标记神经干细胞／前体细胞,然后用免疫细胞化学技术检测大鼠DG中BrdU及nestin阳性细胞。为了解强制运动后DG增殖细胞的功能意义,采用Y-迷宫检测大鼠的学习能力。结果表明,强制运动组DG中BrdU及nestin阳性细胞数均日月显多于对照组（P〈0．05）：强制运动对DG神经发生的效应有强度依赖性。Y-迷宫检测结果显示,强制运动能明显改善大鼠的学习能力。结果提示,在转轮中进行强制跑步能促进成年火鼠DG的神经发生,并改善学习能力。     

Interrelationship between immunologic and neurologic memory: learning ability of rats during immunostimulation]

Studies have been made on the effect of an immunostimulator - the complete Freund's adjuvant - upon the learning ability in Wistar rats for visual discrimination using food-obtaining and avoidance of the electric shock techniques. Injection of the adjuvant significantly increases learning ability provided negative reinforcement technique is used, but inhibits the former under the conditions of positive reinforcement. Analysis of the extinction of the conditioned reflexes yielded similar results. Possible relation of immunogenesis to the formation of memory is discussed.     

Pomegranate (Punica granatum L.) flower improves learning and memory performances impaired by diabetes mellitus in rats

Oxidative stress induced by diabetes mellitus leads to damages in the brain, as a consequence of which cognitive functions is impaired. Therefore, for the treatment of diabetes mellitus, in addition to antidiabetics, antioxidants are used to cope with oxidative stress. The antioxidant ability of pomegranate flowers (PGF) to cope with the oxidative stress was investigated. Rats were divided into five groups with 12 animals in each group as given below: control, diabetes (STZ), STZ + the PGF I (300 mg/kg/day), STZ + PGF II (400 mg/kg/day) and STZ + PGF III (500 mg/kg/day).The findings from Morris water maze and probe tests showed that the animals in STZ group had impairments in learning and memory performances compared to the control group. Supplementation of PGF led to improvements in learning and memory performances of diabetic rats.While lipid peroxidation (LPO) was increased (P<0.001), glutathione (GSH) content was decreased (P<0.001) in hippocampal tissue of STZ-induced diabetic rats when compared with control values. Supplementation of PGF restored the levels of LPO and GSH towards their control values. Daily PGF supplementation to diabetic rats reduced the increase in glial-fibrilar acidic protein (GFAP) contents induced by diabetes in the hippocampus, which was significant in STZ + PGF III in comparison to STZ group (p<0.05).In conclusion, these observations suggest that PGF supplementation decreases oxidative stress and ameliorates impairment in learning and memory performances in diabetic rats. Therefore, we suggest that PGF supplementation may be clinically useful in treating neuronal deficit in diabetic patients.     

钙调神经磷酸酶信号通路参与前列腺素F2α诱导的心肌肥厚

利用野百合碱（monocrotaline,MCT）诱导大鼠右心室肥厚模型和培养乳鼠心肌细胞,研究前列腺素F2α（prostaglandin F2α,PGF2α）在心肌肥厚中的作用及钙调神经磷酸酶（calcineurin,CaN）信号通路征其中的作用。在雄性Sprague-Dawley大鼠中,用MCT（60mg／kg）单次i．p．诱导右心室肥厚,同时用塞来旨布（20mg／kg）预防／治疗给药2周。用病理检测、电镜观察等方法观察心肌肥厚时组织病理改变;EIA试剂盒检测心肌组织PGF2α含量;RT-PCR检测心房钠尿肽（atrial natriuretic peptide,ANP）和CaNmRNA的表达;用蛋白免疫印迹法检测CaN及其下游因了NFAT3和GATA4蛋门质的表达。以心肌细胞直径、蛋白含量和ANP mRNA表达的变化为0．1μmol／L PGF2α诱导心肌细胞肥大的指标。以CaN mRNA表达作为该信号通路的主要指标,并观察CaN抑制剂环孢素A对PGF2α所致心肌细胞肥人和CaN mRNA表达的影响。结果显示：MCT注射2周（M2W组）,右心室肥厚指数（RVHI）、右心室／体重比及肺重／体重比分别增加了47％、53％和118％;注射后4周（M4W组）增加了64％、94％及156％。电镜观察发现右心室组织损伤。同时,右心室组织PGF2α含量在M2W和M4W组分别增加了44％和51％,与RVHI、ANP和CaN的mRNA表达,及CaN／NFAT3／GATA4的蛋白质表达均呈正相关。环氧酶抑制剂塞来昔布预防和治疗给药均明显改善MCT诱导的组织病理学改变。在高体细胞培养中,PGF2α（0．1μmol／L）明显使心肌细胞增大,蛋白质含量增加,ANP和CaN mRNA表达增强：同时,CaN抑制剂环孢素A明显抑制PGF2α诱导的心肌细胞肥大和CaN mRNA表达。上述结果提示：心肌组织局部PGF2α参与了MCT诱导的心肌肥厚过程,CaN信号通路是其细胞内信号转导通路之一。     

The phosphate carrier has an ability to be sorted to either the TIM22 pathway or the TIM23 pathway for its import into yeast mitochondria

Most mitochondrial proteins are synthesized in the cytosol, imported into mitochondria via the TOM40 (translocase of the mitochondrial outer membrane 40) complex, and follow several distinct sorting pathways to reach their destination submitochondrial compartments. Phosphate carrier (PiC) is an inner membrane protein with 6 transmembrane segments (TM1-TM6) and requires, after translocation across the outer membrane, the Tim9-Tim10 complex and the TIM22 complex to be inserted into the inner membrane. Here we analyzed an in vitro import of fusion proteins between various PiC segments and mouse dihydrofolate reductase. The fusion protein without TM1 and TM2 was translocated across the outer membrane but was not inserted into the inner membrane. The fusion proteins without TM1-TM4 were not inserted into the inner membrane but instead translocated across the inner membrane. Functional defects of Tim50 of the TIM23 complex caused either by depletion of the protein or the addition of anti-Tim50 antibodies blocked translocation of the fusion proteins without TM1-TM4 across the inner membrane, suggesting that lack of TM1-TM4 led to switch of its sorting pathway from the TIM22 pathway to the TIM23 pathway. PiC thus appears to have a latent signal for sorting to the TIM23 pathway, which is exposed by reduced interactions with the Tim9-Tim10 complex and maintenance of the import competence.     

Better to be bimodal: the interaction of color and odor on learning and memory

Defended prey frequently advertise to potential predators usingmultimodal warning displays. Signaling through more than onesensory pathway may enhance the rate of avoidance learning andthe memorability of these learned avoidances. If this is so,then mimetic insects would gain more protection from mimickinga multimodal rather than a monomodal model. Day-old domesticchicks (Gallus gallus domesticus) were used to examine whethera common insect warning odor (pyrazine) enhanced learning andmemorability of yellow prey, a common warning color. Pyrazineincreased the rate at which the chicks learned to avoid unpalatableyellow prey, and how well this learned avoidance was rememberedafter a 96-h interval. After 96 h, mimics of the multimodalprey were avoided, whereas mimics of the monomodal prey werenot. In the absence of pyrazine, chicks generalized their learnedavoidance of the unpalatable yellow prey to palatable greenprey; however, the presence of pyrazine reduced this color generalization.These results suggest that much is to be gained from signalingmultimodally, for both models and mimetic prey species. Thepresence of multimodal prey in the habitat may also advantagethe predators as it allows it them to distinguish more easilybetween palatable and unpalatable prey.     

鲍肽素对血管性痴呆大鼠学习与记忆能力的干预及机制研究

目的：观察鲍肤索对血管性痴呆大鼠学习与记忆能力的干预及机制。方法：制备生物鲍肤索,分剂量喂饲血管性痴呆大鼠,测试学习与记忆能力、红细胞和血红蛋白。结果：鲍肤素提高大鼠Y型迷宫测试的分值和红细胞、血红蛋白水平。结论：鲍肤素能提高血管性痴呆大鼠的学习与记忆能力和红细胞、血红蛋白水平。     

银杏叶提取物对糖尿病大鼠学习记忆能力及海马神经元NGF、NT-3表达的影响

目的:探讨银杏叶提取物(EGB)对Ⅰ型糖尿病大鼠海马神经元神经生长因子(NGF)和神经营养因子-3(NT-3)表达的影响。方法:30只雄性SD大鼠随机平分为3组(n=10):CON组,DM组,EGB组。应用链脲佐菌素腹腔注射诱导构建糖尿病大鼠模型,EGB组腹腔注射EGB注射液,其余2组给予同容积的生理盐水。动态观察大鼠行为、体重及血糖水平的变化。于12周末用Morris水迷宫检测大鼠学习记忆能力,常规HE染色观察海马组织形态学改变,用Western bot和RT-PCR法检测大鼠海马组织中NGF、NT-3的表达。结果:与糖尿病组相比,EGB组大鼠行为、体重(P<0.05)和血糖(P<0.05)明显改善;Morris水迷宫潜伏期明显缩短(P<0.05)、搜索策略能力明显提高(P<0.01);HE染色显微镜观察海马组织病理改变减轻;Western bot和RT-PCR分析表明EGB组大鼠海马组织中NGF、NT-3表达均明显增高(P<0.05)。结论:EGB改善糖尿病大鼠的认知功能,其机制可能与EGB增加海马神经元NGF、NT-3的表达,减少神经元凋亡有关。     

Low (20 cGy) doses of 1 GeV/u (56)Fe--particle radiation lead to a persistent reduction in the spatial learning ability of rats

Exposure to galactic cosmic radiation (GCR) is considered to be a potential health risk in long-term space travel, and it represents a significant risk to the central nervous system (CNS). The most harmful component of GCR is the HZE [high-mass, highly charged (Z), high-energy] particles, e.g. (56)Fe. In previous ground-based experiments, exposure to high doses of HZE-particle radiation induced pronounced deficits in hippocampus-dependent learning and memory in rodents. Recent data suggest that glutamatergic transmission in hippocampal synaptosomes is impaired after low (60 cGy) doses of 1 GeV/u (56)Fe particles, which could lead to impairment of hippocampus-dependent spatial memory. To assess the effects of mission-relevant (20-60 cGy) doses of 1 GeV/u (56)Fe particles on hippocampus-dependent spatial memory, male Wistar rats either received sham treatment or were irradiated and tested 3 months later in the Barnes maze test. Compared to the controls, rats that received 20, 40 and 60 cGy 1 GeV/u (56)Fe particles showed significant impairments in their ability to locate the escape box in the Barnes maze, which was manifested by progressively increasing escape latency times over the 3 days of testing. However, this increase was not due to a lack of motivation of the rats to escape, because the total number of head pokes (and especially incorrect head pokes) remained constant over the test period. Given that rats exposed to X rays did not exhibit spatial memory impairments until >10 Gy was delivered, the RBE for 1 GeV/u (56)Fe-particle-induced hippocampal spatial memory impairment is ～50. These data demonstrate that mission-relevant doses of 1 GeV/u (56)Fe particles can result in severe deficits in hippocampus-dependent neurocognitive tasks, and the extreme sensitivity of these processes to 1 GeV/u (56)Fe particles must arise due to the perturbation of multiple processes in addition to killing neuronal cells.     

Characteristics of the action of psychostimulants on learning and memory in rats

The effects of intraperitoneal injections of psychostimulant drugs: centrophenoxine (50 mg/kg) and peptide analog of tuftsin TP-1 (300 micrograms/kg) on the processes of elaboration and retention of conditioned reflex have been experimentally studied. The animals were trained with food reward in 30 trials per day. Psychostimulant drugs or saline were injected after the 10th trial. The elaboration of conditioned reflex was continued 30 min later. The retention was tested 24 h, 7 and 30 days later. It was established that both drugs induce an increase in memory traces stability during 30 days. These findings provide direct evidence that psychostimulant drugs, centrophenoxine and peptide substance TP-1, when injected during consolidation phase can enhance memory storage processes.     

参乌胶囊及其有效成分二苯乙烯苷对老年大鼠海马区神经生长因子及其受体表达的影响

目的观察本室自行研制的中药新复方参乌胶囊（SW）及其有效成分何首乌四羟基二苯乙烯苷（TSG）对老年大鼠海马区神经生长因子（NGF）及其受体表达的影响。方法老年sD大鼠从21月龄始,分别灌胃给予SW低、高剂量（0．8s／kg、1．6g／kg）和TSG低、高剂量（0．03s／kg、0．06g／kg）至24月龄。以6月龄大鼠为青年对照,未给药的24月龄大鼠为老年对照。应用实时定量PCR方法检测大鼠海马区NGF及其受体TrkA的mRNA表达水平,免疫组织化学染色和Westernblot方法检测海马区NGF及TrkA表达水平。结果从基因和蛋白质水平观察到,老年大鼠海马区NGF及其受体TrkA的mRNA表达和蛋白表达明显降低。老年大鼠灌胃给予SW能够上调其海马区NGFmRNA和TrkAmRNA水平;SW和TSG对NGF蛋白表达有明显的增高作用,高剂量SW和TSG对TrkA表达的上调作用显著。结论SW和TSG能够增高老年大鼠海马区NGF及其受体水平,提示它们可作用在神经元信号转导通路的起始端,有利于提高神经元的存活和功能。     

Effect of exposure to high pressure on subsequent spatial learning and memory in rats

The effects of high helium pressure on the subsequent acquisition of spatial memory were studied in male rats. Thirty-two rats were exposed to 65 ATA helium-oxygen pressure for 4.2 days, decompressed (total time in chamber 5 days), and then tested in an eight-arm radial maze. Thirty-two control rats were exposed in the chamber to 1 ATA air. Each rat had 20 sessions in the maze (2 sessions/day for 10 days), and the number of correct (visiting an arm not previously visited to obtain the reward pellet) and incorrect choices (visiting a previously visited arm) were recorded. Statistical analysis showed that the rats exposed to 65 ATA performed significantly better than 1-ATA controls during the first 8 of 20 sessions. This effect was most pronounced in sessions 5-8. Results for sessions 9-20 showed that the pressure-treated rats still made more correct choices but to an extent that did not always reach statistical significance. Possible explanations include the pressure-treated rats performing better because of hunger after a lower food consumption at pressure. Alternatively, pressure itself may enhance proposed mechanisms of spatial memory such as long-term potentiation.     

Studies on the development of water maze-learning ability in rats (3). Effect of the learning schedule on learning acquisition

The effect of different learning schedules massed or distributed practice conditions (3 trials a day for 3 days), on water-filled multiple T-maze learning ability of 8-week-old SPF Wistar-Imamichi rats was investigated. Although the mean number of errors decreased day by day in both groups, the number of errors in a given day and the total number of errors in 3 days did not differ significantly between the two groups. A tendency toward a decrease in the number of errors was observed as the trials proceeded in the group with distributed practice but not in the group with massed practice. The result suggests that a certain time period for rest after each trial is necessary to acquire the memory.     

The sequence asymmetry of the Escherichia coli chromosome appears to be independent of strand or function and may be evolutionarily conserved.

I have examined potential determinants of the asymmetric distribution of nucleotide sequences in the genome of Escherichia coli as cataloged in GenBank release 44. I have used the frequency of occurrence of all possible tetranucleotides in a given sequence catalog or derivative as a comparative measure of asymmetry. The GenBank-cataloged strand and its complement show statistically similar (not complementary) distributions. The distribution is statistically similar in comparisons between the protein coding subset and the total genome, the coding subset and selected non-coding genes, the coding subset and the remainder of the DNA, and the coding subset and stable RNA sequences. I have compared the distribution in the genome of E. coli with the distributions found in the cataloged genomes of Salmonella typhimurium, Bacillus subtilis, and of coliphages lambda and T7. The distribution summed in both strands of the cataloged DNA differs statistically only in comparisons with lytic bacteriophage T7 because only the two strands of T7 show statistically dissimilar distributions. Despite similarities in tetranucleotide distribution, the pattern of codon complementarity in B. subtilis is different than that documented for E. coli. Thus, sequence asymmetry does not seem related to specific DNA function or to documented similarities or differences in codon bias. The sequence asymmetry of the E. coli genome may thus reflect a hitherto unsuspected pattern impressed on both strands of DNA which is or can be packaged into bacterial genomes.