Effects of sodium overload on memory parameters and oxidative status of rat brain cortex

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.

Objective To investigate the neurotoxicity of β-amyloid protein (Aβ) in vivo and its effects on rats' learning and memory ability. Methods The aggregated Aβ(25-35) was injected bilaterally into entorbi- hal cortex(EC) of rats. Control rats were injected with saline water. All rats were subjected to Y-maze task at 7 d and 8d after operation. After behavioral testing, the rats were sacrificed. The neurpathological changes of EC were examined by Nissl staining, HE staining and Congo Red staining. Results The cumulative number of electric shocks in acquisition test and retention test of the saline group was 19.17±5.58 and 10.56±1.72 31 respectively. The corresponding number in Aβ-treated rats was 31.13±6.98 and 18.47±4.64, and significantly increased compared with control group (P<0.05). A Congo Red-positive deposit of aggregated material was found at Aβ injection site accompanied by neurons loss and gliacyte reaction. The damaged area of Aβ-treated rats was significandy greater than that of control rats and was negatively correlated with the learning ability (r=-0.241, P < 0.05). Conclusion Bilateral injection of aggregated Aβ into EC induces behavioral deficits and amyloid pathology similar to those observed in early phases of AD. These results show definite neurotoxicity of Aβ in vivo. Therefore, injection of Aβ into EC constitutes a promising animal model for investigating selective aspects of AD and for screening drug candidates designed against Aβ pathology. Key words: Alzheimer's disease; Entorhinal cortex; Amyloid-beta protein; Learning and memory ability

Consumption of high fat diet (HFD) increases risk of cognitive impairment and memory deficit by elevation of oxidative stress in the brain. In this study, we investigated the protective effects of krill oil (KO) against HFD-induced cognitive impairment in mice. The mice were fed with HFD for 10 weeks, and then KO was orally administered at doses of 100, 200, or 500 mg/kg/d for 4 weeks. To evaluate the cognitive abilities, we carried out the behavior tests, such as T-maze, novel object recognition test, and Morris water maze test. The HFD-induced cognitive impairment mice showed impairments in both spatial memory and novel object cognitive abilities. However, administration of KO at doses of 100, 200, or 500 mg/kg/d improved spatial memory ability and novel object cognition by increase of the exploration of new route and novel object. In addition, KO-administered group improved learning and memory abilities, showing shorter latency to reach hidden platform compared with control group. Furthermore, levels of reactive oxygen species (ROS), lipid peroxidation, and nitric oxide (NO) were significantly elevated by consumption of HFD, indicating that consumption of HFD induces oxidative stress in the brain. However, administration of KO attenuated oxidative stress by decrease of the ROS levels, lipid peroxidation, and NO. This study suggests that KO improves HFD-induced cognitive impairment by attenuation of oxidative stress in the brain. Therefore, KO may play as a promising agent in treatment and prevention of HFD-induced cognitive impairment.

Objective To explore the effects of acanthopanax senticosus injection(ASI) on the learning and memory abilities, and the expression of f-actin in hippocampus of cerebral anoxia rats. Methods Thirty-six SD male rats were randomly divided into three groups on average and then 24 rats were left for the other rats were not adapted to the environment. The model group rats (n=8) and the ASI group rats (n=8) were injected embolic fluid via carotis internal arteries to make cerebral model. The normal control rats (n=8) were injected equal dose saline. After 3 days, 90 mg/(kg·d) ASI was intraperitoneal injected to ASI group rats for 7 days. The model group and the control group received equal dose saline via intraperitoneal injection every day for 7 days. After that, the learning and memory abilities were tested by Morris water maze detection. Subsequently, the expression of f-actin in hippocampus was measured. The latency, the traveling distance and the expression of f-actin were analyzed by one-way ANOVA and pairwise comparison used LSD method. Results From 1 to 4 days, the latency in the control group were (48.31±17.13)s, (30.25±16.02)s, (24.25±14.87)s and (14.09±9.06)s, in the model group were (54.94±13.09)s, (48.85±17.21)s, (38.41±21.01)s and (26.13±15.82)s, in the ASI group were (52.28±14.95)s, (36.66±16.90)s, (28.38±15.83)s and (17.03±12.14)s, the differences were statistically significant (F=10.29, 48.19, 156.64, 168.74, all P<0.05). The traveling distance in the control group were (925.54±98.69)cm, (594.47±117.33)cm, (382.38±71.17)cm and (226.58±23.82)cm, in the model group were (1 033.61±125.20)cm, (902.10±145.52)cm, (698.86±121.05)cm and (467.27±107.18)cm, in the ASI group were (930.36±124.51)cm, (662.17±145.40)cm, (412.42±73.98)cm and (233.36±32.48)cm, the differences were statistically significant (F=27.30, 10.21, 5.58, 7.88, all P<0.05). The positive expressions of f-actin in hippocampus were 0.14±0.01, 0.09±0.01, 0.11±0.01 in control group, model group and ASI group, respctively, the difference was statistically significant (F=104.37, P<0.05). Conclusion Acanthopanax senticosus injection can alleviate the symptoms and improve the abilities of learning and memory in brain hypoxia rats. Key words: Acanthopanax; Hypoxia, brain; F-actin; Learning and memory abilities; Rats

PurposeAlthough the onset mechanism of Alzheimer’s disease, which co-occurs with aging, has been extensively studied, no effective methods that improve the decline in memory and learning abilities following aging have been developed. Tranexamic acid provided promising results for ameliorating photo-aging and extending the natural lifespan. However, it is unknown whether it affects the decline in memory and learning abilities due to aging. In this study, we examined the effect of tranexamic acid on memory and learning abilities of naturally aging mice.MethodsICR mice were orally administered with tranexamic acid (12 mg/kg/day) three times weekly for 2 years, and their memory and learning abilities were compared between the tranexamic acid-treated and non-treated groups.ResultsThe decline in memory and learning abilities due to aging was ameliorated by tranexamic acid administration. The expression of plasmin and amyloid-β decreased following the treatment with tranexamic acid. Furthermore, the number of M1-type brain macrophages diminished and that of M2 macrophages increased. In addition, administration of tranexamic acid decreased the concentrations of interleukin (IL)-1β and tumor necrosis factor-α, while it increased the levels of IL-10 and transforming growth factor-α in the brain.ConclusionThese results indicated that tranexamic acid suppressed the secretion of the inflammatory cytokines aging M1-type macrophages, thereby improving age-related memory and learning abilities.

Spatial learning and memory deficits in young adult mice exposed to a brief intense noise at postnatal age

Alzheimer's disease (AD) is a typical neurodegenerative disease with a complex etiology. Until now, there has been no effective treatment available for AD; however, improving energy dysmetabolism, the key pathological event in the early stage of AD, can effectively delay the progression of AD. This paper aims to investigate the therapeutic effect and potential mechanism of the new Tiaoxin recipe on early AD. APP/PS1 mice were divided into a model group, a new Tiaoxin recipe group, and a donepezil group, and C57/BL mice were used for the control group. Mouse cognitive and learning abilities were tested using the Morris water maze test and a new object-recognition experiment. The 42 amino acid form of amyloid β peptide (Aβ1-42) content was detected by enzyme-linked immunosorbent assay, the senile plaque area was detected by thioflavin S staining, and the senescence- associated β-galactosidase (SA-β-gal)-positive area was detected by chemical staining. Also, the adenosine triphosphate (ATP), nicotinamide adenine dinucleotide (NAD+), and nicotinamide adenine dinucleotide hydride (NADH) contents were detected using a biochemical method, and the cluster of differentiation 38 (CD38) and silent mating-type information regulation 2 homolog 3 (SIRT3) protein expression levels were detected by immunofluorescence and Western blot analysis. Compared with those of the control group, the learning and memory abilities of the model group were impaired; the senile plaque deposition, Aβ1-42 content, and SA-βgal-positive staining area were increased; the ATP concentration, NAD+ concentration, and NAD+/NADH ratio were decreased; the CD38 protein expression level was increased; and the SIRT3 protein expression level was decreased. Following intervention with the new Tiaoxin recipe, the learning and memory abilities were improved; the senile plaque deposition, Aβ1-42 content, and SA-βgal-positive area were reduced; the ATP concentration, NAD+ concentration, and NAD+/NADH ratio were increased; CD38 protein expression was decreased, and SIRT3 protein expression was increased. This study shows that the new Tiaoxin Recipe can improve cognitive ability and reduce the Aβ1-42 content and senile plaque deposition in APP/PS1 mice, which may occur through the downregulation of CD38 protein expression, upregulation of SIRT3 protein expression, restoration of the NAD+ level, promotion of ATP synthesis, mitigation of energy metabolism disorders.

Objective To investigate the effects of regular and irregular mandatory treadmill running (TR) on learning and memory abilities,stress response,survival and maturation of newborn neurons in dentate area of C57 mice. Methods Forty-eight male C57BL/6 mice were randomly divided into regular running group (n=16,definite time and quantity), irregular running group (n=16,definite time and different quantities) and sedentary group (n=16).Injection of bromodeoxyuridine (BrdU,50 mg/kg) was given intraperitoneally to mice from the 1st d to the 7th d of exercise,and then,these mice were subjected to a 4-wk TR training course or sedentary exercise.Double irnmunofluorescence labeling was employed to observe the effect of TR on survival and maturation of newborn neurons. Mice were trained on the Morris water maze to test the abilities of learning and memory. Corticosterone (CORT).level in the venous blood was measured with a radioimmunoassay kit. Results As compared with that in mice of the irregular running group and sedentary group,significant decrease of latency was noted in mice of the regular running group on the 1st, 3rd, 4th and 5th d of place navigation test (P＜0.05). As compared with that in mice of the sedentary group, significant decrease of latency was noted in mice of the irregular running group and regular running group on the 2nd d of place navigation test (P＜0.05),while no significant difference of that was noted between mice of the irregular running group and regular running group (P＞0.05).The platform was removed for a 60-s probe test 4 h after the last trial to test the recall ability, and the times of staying in the target zone in each group were regular running group＞irregular running group＞control group, and significant difference was noted between each 2 groups (P＜0.05). The numbers of double immunofluorescence labeled cells in the dentate gyrus were counted as regular running group＞irregular running group＞control group, and significant difference was noted between each 2 groups (P＜0.05). The serum CORT level was measured as regular running group＜irregular running group＜control group, and significant difference was noted between each 2 groups (P＜0.05). Conclusion Mandatory treadmill running could improve the learning and memory abilities,which may be related to the increment of survival and maturation of neural precursor cells,and decreased level of serum CORT; and the effect of regular mandatory treadmill running is better than that of irregular mandatory treadmill running. Key words: Exercise training; Neural precursor cell; Neurogenesis; Learning and memory

In order to investigate the anti-aging effect and mechanism of Liuwei Dihuang Wan pill (LWDH) on natural aging rats, LWDH pill was abstracted by boiling and filtrating according to conventional method and became decoction. Adult male rats were divided into two groups randomly, the experimental group fed with decoction of LWDH (0.5 mg/ml/100 g body weight), and natural aging group fed with equivalent volume of tap water. Both groups were treated with respective material once each day for one year. Morris water maze was employed to examine the behavioral learning and memory ability of all rats in the experiment. The content of superoxide dismutase (SOD), an antioxidant, and acetylcholinesterase (AChE) in serum were tested with spectrophotometer. The activity of choline acetyltransferase (ChAT) in brain cortex was assayed by spectrophotometer. The thymus index and spleen index were analyzed. The results showed that LWDH can improve general behavior of aging rats. Compared with the control group, the weight of natural aging rats increased stably and was much higher (P ＜ 0.05). The LWDH-treated rats showed a shorter average escape latency in the navigation test (P ＜ 0.05) and higher percentage of swimming time spent in the target quadrant of Morris water maze and later spatial probe test (P ＜ 0.05). Higher thymus index and spleen index (P ＜ 0.05), increased SOD vigor in serum (P ＜ 0.05) as well as higher ChAT and AChE in cerebral cortex (P ＜ 0.05) were also observed. As above, LWDH can improve learning and memory ability and general behavior of natural aging rats; it can also reverse the metabolic capability and immunoregulation in natural aging rats.

Objective To study the changes of learning and memory ability in fos-GFP transgenic mice. Methods The mice in the fos-GFP group and the control were tested by using overhead cross maze,open field,and Morris Water Maze[1]. The spontaneous activity,anxiety state,the ability of learning and memory were tested as well. Results The differences between fos-GFP mice and the control were not significant in terms of distance of motion within the field,velocity,duration of stay at the marginal zone,and duration of open arm in the maze(p>0.05).The difference between the mice in the two groups was not significant with regard to latency of finding the flat at each time point(p>0.05),and the percentage of duration in target quadrant in Morris Water Maze(p>0.05),and similar freezing time in contextual fear conditioning test(p>0.05).The fos-GFP mice showed higher freezing level than normal controls in no-exposed fear conditioning(t=9.48,P<0.001). Conclusion The ability of hippocampus-dependent associative learning and memory in fos-GFP transgenic mice was somewhat improved.

Oysters (Crassostrea talienwhanensis) contain large amounts of protein and exhibit many biological activities. This study was aimed at preparing oyster protein hydrolysates (OPH) and evaluating the OPH based on a spatial learning and memory capacity. A response surface methodology was employed to optimize hydrolysis conditions to determine the OPH with the highest AChE inhibitory activity, and the optimum extraction conditions were as follows: enzyme concentration of 1444.88 U g−1, pH of 7.38, extraction temperature of 45 °C, extraction time of 5.56 h and a water/material ratio of 2.45 : 1, and the minimum acetylcholinesterase (AChE) activity was 0.069 mM min−1. The spatial memory and learning abilities and passive avoidance in mice were determined by using the Morris water maze test and a dark/light avoidance test. Furthermore, the OPH group could relieve oxidative stress, reduce AChE levels, increase choline acetyltransferase (ChAT) levels and alleviate inflammatory reaction through reduction of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels. Additionally, up-regulated expressions of brain-derived neurotrophic factor (BDNF) and neural cell adhesion molecules (NCAM) were observed in mice treated with OPH. These findings suggested that OPH could be a functional food candidate to improve the learning and memory ability associated with oxidative stress and inflammatory reactions.

Objective To explore the influence of environment early in life on learning and memory abilities and neuroglobin (Ngb) expression. Methods Forty-five newborn,male,Sprague-Dawley rats were randomly divided into an EE (enriched environment) group,an EI (isolated environment) group and a normal control group,with 15 rats in each group.The EE and EI group rats lived in those environments for their first 28 days of life.The step-down test was used to measure the rats'learning and memory abilities on the 29th day.Ngb expression was examined using immunohistochemical methods. Results The step-down test showed learning and memory scores for the EE group rats of (9.67±0.49) and (9.80±0.56) respectively,significantly higher than those of the control group,(8.67±0.72) and (8.93±1.10).The learning and memory abilities of the EI group were the lowest among the three groups,with scores of only (7.07±1.98) and (7.67±0.98 ),respectively.The latency of the first electric shock was (166.33±36.08)s in the EE group and significantly shorter than that in the control group (108.93±73.26) s.The EI group showed the longest average latency (44.93±45.03)s.Average Ngb expression as reflected by the integrated optical density in the EE group was (224.56±89.09) in the frontal cortex and (127.70 ± 28.16)in the hippocampus,a significant increase over expression in the control group.The Ngb expressions of the EI group were the lowest among the 3 groups-(88.78 ± 18.84) and ( 63.42 ± 16.41 ) in the frontal cortex and hippocampus respectively. Conclusions Early exposure to an enriched environment can increase Ngb expression and improve learning and memory ability,but early isolation will reduce Ngb expression and learning and memory function. Key words: Early environment; Neuroglobin; Learning; Memory

By 3 to 4 months of age, infants born full-term and without known disease display associative learning and memory abilities in the mobile paradigm, where an infant's leg is tethered to a mobile such that leg kicks result in proportional mobile movement. The first purpose of this study was to examine the learning and memory abilities of a group of infants born full-term compared with those of a comparison group. Little is known about the learning and memory abilities in infants born preterm, a group at known risk for future impairments in learning and movement. The second purpose of this study was to determine if and when an age-adjusted group of infants born prematurely display associative learning and memory abilities over a 6-week period. Ten infants born full-term (38-42 weeks gestational age [GA]) and 10 infants born preterm (<33 weeks GA and <2,500 g) who were tethered and had control over the mobile movement were independently compared with a comparison group of 10 infants born full-term who were tethered and viewed a moving mobile but did not have control over the mobile movement. Infants in all 3 groups were seen at 3 to 4 months of age and were excluded from participation for any known visual or orthopedic diagnoses. Infants were tested using the mobile conjugate reinforcement paradigm, where one leg is tethered to an overhead mobile such that kicking with that leg results in proportional mobile movement. The kicking rates of the full-term group and the preterm group were compared with their own initial (baseline) kicking rates and with those of the comparison group. After exposure to the conjugate relationship between kicking and mobile movement, the full-term group kicked more frequently compared with their own baseline levels and compared with the comparison group, fulfilling both criteria for learning and memory. In contrast, the preterm group did not increase their kicking rate according to both criteria. These results suggest that infants born prematurely differ in their performance in the mobile paradigm as compared with age-matched infants born full-term. The mobile paradigm may provide clinicians with an important early assessment of infants' associative learning and memory abilities. Follow-up studies are needed, however, to further validate this paradigm as a clinical assessment tool.

The prevalence of insulin resistance syndrome increases during menopause with the overproduction of reactive oxygen species and impairment of the free radical scavenger function. Therefore, we investigated the effects of 17β-estradiol (E(2)) and vitamin E, as an antioxidant, on lipid peroxidation and antioxidant levels in the brain cortex and liver of ovariectomized rats as well as on insulin resistance in those rats. Forty female Sprague-Dawley rats, 3months of age and weighing 231.5± 9.4 g, were divided into 4 groups: sham, ovariectomized (OVX), OVX treated with E(2) (40 µg/kg subcutaneously), and OVX treated with E(2) and vitamin E (100mg/kg intraperitoneally). The 4 groups received the appropriate treatment every day for 8weeks. Levels of glutathione, glutathione peroxidase, superoxide dismutase , catalase, and malondialdehyde in the brain cortex and liver of ovariectomized rats were measured. Also, fasting plasma insulin, glucose, and homeostatis model assessment of insulin resistance (HOMA-IR) were determined. Malondialdehyde increased and antioxidants (glutathione, glutathione peroxidase, catalase, superoxide dismutase) decreased in the brain cortex and liver of OVX rats. Also, fasting glucose, insulin, and HOMA-IR increased in OVX rats. E(2) and E(2) plus vitamin E decreased malondialdehyde and increased antioxidants in the brain cortex and liver of OVX rats. Moreover, they decreased fasting glucose, insulin, and HOMA-IR in ovariectomized rats. This study demonstrates that E(2) and E(2) plus vitamin E supplementation to OVX rats may improve insulin resistance, strengthen the antioxidant system, and reduce lipid peroxidation.

Effects of Ganoderma on aging and learning and memory ability in senescence accelerated mice