The protective effect of dietary eicosapentaenoic acid against impairment of spatial cognition learning ability in rats infused with amyloid beta(1-40)

BackgroundAmyloid β (Aβ) peptide (1–40) can cause cognitive impairment.Experimental designWe investigated whether dietary preadministration of eicosapentaenoic acid (EPA) is conducive to cognition learning ability and whether it protects against the impairment of learning ability in rats infused with Aβ peptide (1–40) into the cerebral ventricle.ResultsDietary EPA administered to rats for 12 weeks before the infusion of Aβ into the rat brain significantly decreased the number of reference memory errors (RMEs) and working memory errors (WMEs), suggesting that chronic administration of EPA improves cognition learning ability in rats. EPA preadministered to the Aβ-infused rats significantly reduced the increase in the number of RMEs and WMEs, with concurrent proportional increases in the levels of corticohippocampal EPA and docosahexaenoic acid (DHA) and in the DHA/arachidonic acid molar ratio. Decrease in oxidative stress in these tissues was evaluated by determining the reactive oxygen species and lipid peroxide levels. cDNA microarray analysis revealed that altered genes included those that control synaptic signal transduction, cell communication, membrane-related vesicular transport functions, and enzymes and several other proteins.ConclusionThe present study suggests that EPA, by acting as a precursor for DHA, ameliorates learning deficits associated with Alzheimer's disease and that these effects are modulated by the expression of proteins involved in neuronal plasticity.     

Tetrahydroxystilbene glucoside improves learning and (or) memory ability of aged rats and may be connected to the APP pathway

The aim of this study is to evaluate the protective effects of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) on learning and (or) memory deficit in aged rats, as well as to explore the possible connection between TSG and the β-amyloid precursor protein (APP) pathway. Sprague-Dawley rats were randomly divided into a young control group (age, 4?months), an aged control group (age, 22?months), and a TSG-treated group (age, 22?months). TSG at doses of 50?mg·kg(-1)·day(-1) was intragastrically administered to 22-month-old rats for 4?weeks. The learning and (or) memory ability was measured using the Morris water maze (MWM) test, and the mRNA and protein expression of APP pathway proteins was measured by real-time polymerase chain reaction (RT-PCR) and Western blot, respectively. The aged rats exhibited obvious learning and (or) memory deficit when compared with the young rats, but TSG treatment significantly improved the learning and (or) memory ability in the aged rats, as noted from the MWM test. RT-PCR and Western blot analysis showed an increase in the expression of beta-site APP cleaving enzyme 1 (BACE1) and A Disintegrin And Metalloproteinase 17 (ADAM17) in aged rats, and a decrease in ADAM10; however, TSG treatment significantly increased the mRNA and protein expression of ADAM10 (p?< 0.01, compared with aged control rats). These results provide solid evidence for the therapeutic effect of TSG on age-related cognitive impairment, especially spatial learning and memory deficit. TSG might exert this effect through the APP pathway, although further studies on the topic are required.     

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.     

Ageing does not significantly affect performance in a spatial learning task in the domestic cat (Felis silvestris catus)

A spatial learning task was used to examine cognitive function in 36 cats (1.0–15.1 years of age), with a control for motor function. No significant age-related decline in cognitive function was found. Initial selection of 75 cats showed no significant age differences between young (0–3 years), adult (3.1–8 years), senior (8.1–12 years) and geriatric cats (12.1–15.1 years) locating food rewards in a holeboard box. Consequently, the senior and geriatric groups were combined because of a concern that age effects may not be seen in the 8–12-year-old cats. Differences between these three age groups of cats to learn the position of three food rewards in an array of 30 otherwise empty (food-scented) positions were non-significant. Differences between age groups remained non-significant for retrieval of rewards from these three positions even when masked with a tissue paper cover. There was no significant effect of age on speed of reaching each criterion. Although the total number of errors was similar, there was a significantly increased proportion of working memory errors (when the cat returned to a previously baited position) and decreased proportion of reference memory errors (when the cat put a nose or paw in an empty position) with increasing age. There was no effect of age on motor function, with success in a plank-crossing test related only to plank width. These findings support previous work suggesting that the cat differs from other species in the way in which it demonstrates age-related declines in cognitive function. Further studies using different testing methodologies are required to assess other cognitive functions that may decline with age.     

DT56a (Tofupill/Femarelle) selectively stimulates creatine kinase specific activity in skeletal tissues of rats but not in the uterus

The novel natural product DT56a (Tofupill/Femarelle), derived from soybean, has been shown to relieve menopausal vasomotor symptoms and to increase bone mineral density with no effect on sex steroid hormone levels or endometrial thickness. In the present study, we compared the effects of DT56a and estradiol-17beta (E2) on bone and cartilage (Ep) of immature or ovariectomized female rats, by measuring the changes in the specific activity of the BB isozyme of creatine kinase (CK). Single short-term injection of high doses of DT56a induced estrogenic activity in bones and uterus similar to that of E2. When administered in multiple oral doses, DT56a stimulated skeletal tissues similarly to E2, but whereas E2 increased CK specific activity in the uterus, DT56a did not. The selective estrogen receptor modulator (SERM) raloxifene (Ral) blocked the stimulation of CK by either DT56a or by E2 in all tissues tested. Our findings suggest that DT56a acts as a selective estrogen receptor modulator stimulating skeletal tissues without affecting the uterus. The effect of DT56a on other systems, such as the vascular and the central nervous system, are currently under investigation.     

Low-level exposure to pulsed 900 MHz microwave radiation does not cause deficits in the performance of a spatial learning task in mice

There is some concern that short-term memory loss or other cognitive effects may be associated with the use of mobile cellular telephones. In this experiment, the effect of repeated, acute exposure to a low intensity 900 MHz radiofrequency (RF) field pulsed at 217 Hz was explored using an appetitively-motivated spatial learning and working memory task. Adult male C57BL/6J mice were exposed under far field conditions in a GTEM cell for 45 min each day for 10 days at an average whole-body specific energy absorption rate (SAR) of 0.05 W/kg. Their performance in an 8-arm radial maze was compared to that of sham-exposed control animals. All behavioral assessments were performed without handlers having knowledge of the exposure status of the animals. Animals were tested in the maze immediately following exposure or after a delay of 15 or 30 min. No significant field-dependent effects on performance were observed in choice accuracy or in total times to complete the task across the experiment. These results suggest that exposure to RF radiation simulating a digital wireless telephone (GSM) signal under the conditions of this experiment does not affect the acquisition of the learned response. Further studies are planned to explore the effects of other SARs on learned behavior. Bioelectromagnetics 21:151-158, 2000. Published 2000 Wiley-Liss, Inc.     

NR2B、pERK、pElk-1共同参与大鼠逃避性学习和记忆

目的：探讨NR2B-pERK—pElk-1途径是否参与了大鼠各学习记忆相关脑区Y-迷宫逃避性学习和记忆。方法：健康雄性成年SD大鼠45只,共分为4组：①ifenprodil腹腔注射组（ifenprodilip,14只）,②DMSO腹腔注射组（DMSOip,15只）;③ifenprodil脑室注射组（ifenprodilic,8只）;④DMSO脑室注射组（DMSOic,8只）。以Y迷宫训练和测试成绩作为行为学评定指标,用免疫组织化学和Westernblot方法观察大鼠学习记忆相关脑区pERK1／2和pElk-1的变化。结果：ifenprodilip组与DMSOip组动物的Y迷宫学习成绩没有明显差异（P〉0．05）,但ifenprodilip组Y迷宫记忆成绩差于DMSOip组（P〈0.05）。腹腔注射ifenprodil导致Y迷宫训练后各脑区pERK1／2和pElk-1表达的普遍下降,其中以海马、边缘区、杏仁核最为明显,与DMSOip组相比差异有显著性（P〈0.05）。ifenprodilic组与DMSOic组第一次Y迷宫测试成绩没有明显差异（P〉0.05）。第一次测试后立即脑室给药并在给药后6h测试Y迷宫记忆再巩固成绩,发现ifenprodilic组成绩下降,与DMSOic组相比有明显差异（P〈0．05）,而且ifenprodilic组动物各脑区的pERKl／2和pElk-1表达与DMSOic组相比均普遍下降,其中pElk-1表达在尾壳核和边缘区几乎完全消失。结论：NR2B对于大鼠Y迷宫长期记忆的形成、记忆再巩固过程是必要的．NR2B的失活将破坏这些过程。同时NI毪B的失活减弱了Y迷宫训练后及记忆再巩固测试后学习记忆相关脑区pElk-1和pERK1／2表达,其中在尾壳核和边缘区,NR2B的失活使记忆再巩固测试后pElk-1表达完全被阻断。     

Mechanism of garlic (Allium sativum) induced reduction of hypertension in 2K-1C rats: a possible mediation of Na/H exchanger isoform-1

Garlic causes reduction in blood pressure (BP), however the role of Na/H exchanger (NHE) which mediates hypertension and related tissue-damage is poorly understood. In this study the effect of an established dose of raw garlic extract was investigated on the expression of NHE-1 and -3 and sodium pump activity in a 2K-1C model of hypertension in rats. 2K-1C animals showed high BP, increased serum concentration of PGE2 and TxB2, hypertrophy of the unclipped kidneys, but not in the clipped kidneys In addition, NHE-1 and NHE-3 isoforms were increased in both the 2K-1C kidneys, whereas alpha-actin was increased in the clipped but not in unclipped kidneys. Sodium pump activity was decreased in the clipped kidneys, but remained unchanged in the unclipped kidneys. Garlic treatment reduced the induction of NHE-1 only in the unclipped 2K-1C kidneys, whereas garlic treatment increased the sodium pump activity in both the 2K-1C kidneys. These findings demonstrate that the antihypertensive action of garlic is associated with a reversal of NHE-1 induction in the unclipped kidneys. Induction of NHE isoforms together with a reduced sodium pump activity might cause necrosis in the 2K-1C clipped kidneys due to cellular retention of Na+. On the other hand, activation of sodium pump by garlic extract in the kidneys should reduce intracellular Na+ concentration and normalize BP. These findings signify the use of garlic in the treatment of hypertension.     

The ability of Rhodnius prolixus (Hemiptera; Reduviidae) to approach a thermal source solely by its infrared radiation

The ability of the haematophagous bug Rhodnius prolixus to approach a pure IR source only by its long-wave infrared radiation (IR) was investigated. To exclude any heated air from reaching the bug a cooled IR-transmitting window was placed between the IR-source (a Peltierelement heated to 35 degrees C) and the bug. Starved bugs were tested under invisible short-wave IR illumination (lambda<1 μm) in order to exclude also any visual cues. The number of bugs approaching the IR-source was significantly increased compared to the controls in which the IR-source was turned off (chi(2)-test, P<0.01). Our results show that Rhodnius prolixus can use infrared stimuli to find a host.     

Prenatal exposure to interleukin-6 results in inflammatory neurodegeneration in hippocampus with NMDA/GABA(A) dysregulation and impaired spatial learning

During pregnancy, infection or immune responses induce cytokine release, which might influence fetal neurodevelopment, leading to neurodegenerative disease in adulthood. Because the hippocampus is a key area for learning and memory, we evaluated 4- and 24-wk-old rats for the effects of early and late prenatal exposure to interleukin-6 (IL-6) on hippocampal morphology, expression of mRNA for IL-6, the gamma-aminobutyric acid receptor (GABA(Aalpha5)), the NR1 subunit of the N-methyl-D-aspartate receptor, and glial fibrillary acidic protein (GFAP), caspase-3 protein and mRNA levels, and learning abilities. Late exposure increased serum IL-6 and hippocampal expression of IL-6 mRNA at 4 and 24 wk. All adult rats showed neuronal loss in the hilus and astrogliosis; males had losses mainly in the CA2 and CA3 regions, and females in CA1. Expression of GABA(Aalpha5), NR1, and GFAP mRNA increased in late-exposed males and females at 4 and 24 wk. mRNA and protein levels of the apoptosis marker caspase-3 were increased in all late-exposed rats except males at 4 wk. Evaluation of hippocampus-dependent working memory in the Morris water maze at 20 wk of age showed increases in escape latency and time spent near the pool wall in all IL-6 adult rats, especially females. These findings suggest that fetal IL-6 exposure, especially in late pregnancy, leads to increased IL-6 levels in the circulation and hippocampus, abnormalities of hippocampal structural and morphology, and decreased learning during adulthood.     

Identification of tyrosine-phosphorylated colony-stimulating factor 1 (CSF-1) receptor and a 56-kilodalton protein phosphorylated in intact human cells in response to CSF-1

Colony-stimulating factor 1 (CSF-1) selectively supports the survival, proliferation, and maturation of hemopoietic cells of the monocyte/macrophage lineage. Although the cellular receptor for CSF-1, (the c-fms protein) is a protein-tyrosine kinase activated by the binding of CFS-1, the role of phosphorylation of cellular proteins in CSF-1 signal transduction is poorly understood. Therefore, we examined the CSF-1-stimulated phosphorylation of cellular proteins in human BeWo choriocarcinoma cell line (known to express the c-fms protein). BeWo cells were metabolically labeled with 32Pi, stimulated with recombinant human CSF-1, and extracted with detergent. Phosphotyrosyl proteins were isolated from detergent extracts by affinity chromatography on a highly specific antibody to phosphotyrosine. Rapid phosphorylation of 170-kd protein, followed closely by the phosphorylation of a 56-kd protein, was observed in response to CSF-1. The 170-kd phosphotyrosyl protein bound to wheat germ agglutinin and was secondarily immunoprecipitated with a specific anti-fms serum, consistent with its identity as the CSF-1 receptor. Although purified human macrophages that proliferate in culture in response to CSF-1 are not generally accessible, CSF-1 did stimulate the phosphorylation of a 56-kd protein in intact mononuclear leukocytes from human peripheral blood. Thus, the BeWo cell line may represent a good model for the study of CSF-1-stimulated cellular protein phosphorylation.     

Effects of prenatal exposure to diethylstilbestrol (DES) on hemispheric laterality and spatial ability in human males.

Ten males exposed to diethylstilbestrol (DES), a nonsteroidal synthetic estrogen, during gestation were compared to their matched, unexposed brothers on measures of brain hemispheric specialization for processing nonlinguistic spatial information and cognitive abilities. DES exposure was associated with reduced hemispheric laterality and lowered spatial ability. These data provide direct evidence of a relationship between brain laterality, spatial cognitive ability, and prenatal exposure to hormones in human males. Further, the implications of these findings for understanding sexual differentiation of the human brain are discussed.