The correlation between the severity of hypoxic-ischemic brain damage in neonatal rats and subsequent abnormal neurobehavior / 中国新生儿科杂志

Objective:To assess the severity of hypoxic-ischemic brain damage (HIBD) in neonatal rats and predict the occurrence of subsequent neurobehavioral abnormalities after brain injury by scoring and magnetic resonance imaging (MRI).Methods:7-day-old of 60 Sprague-Dawley (SD) rats were randomly divided into control group (14 rats), sham operation group (14 rats) and HIBD model group (32 rats). HIBD model was established by right common carotid artery dissection with Rice-Vannucci method and hypoxia. Within 24 h after modeling, the rats in the model group were evaluated by general condition score and Longa score, and the surviving rats with moderate and severe HIBD were selected for the experiment. 24 h after modeling, 5 rats of the model group were randomly selected for 2,3,5-triphenyltetrazole chloride staining to verify cerebral infarction. 1 week after modeling, 6 rats from each group were randomly selected for hematoxylin-eosin staining to observe HIBD brain injury. 4 weeks after modeling, 4 rats were randomly selected from the control group and the sham operation group, and 8 rats from the remaining model group were used to evaluate the volume of brain damage by MRI. 5-6 weeks after modeling, the remaining 8 rats from each group were subjected to the Cylinder test, and at 13 weeks, they underwent the Morris water maze test to evaluate their neurobehavior.Results:In HIBD model group, 19 rats with moderate to severe HIBD were selected from 32 rats. 24 h after modeling, cerebral infarction was verified in all rats, indicating moderate to severe HIBD. Brain tissue pathology observed 1 week after modeling revealed predominantly gray matter brain damage. MRI showed that 7 out of 8 rats had moderate to severe HIBD. Compared to the control and sham operation groups, the model group exhibited a significant decrease in the usage rate of the left forelimb in the Cylinder test at 5-6 weeks after modeling ( P<0.05), and the latency period in Morris water maze test was significantly prolonged at 13 weeks after modeling ( P<0.05), and the times of crossing platform quadrant were significantly reduced ( P<0.05). There was no significant difference in the right brain injury volume between 24 h and 4 weeks model group ( P>0.05). The brain injury volume in model group was negatively correlated with the usage rate of left forelimb in cylinder test at 5-6 weeks and the times of crossing platform quadrant in Morris water maze test at 13 weeks ( P<0.05), and positively correlated with latency period in Morris water maze test at 13 weeks ( P<0.05). Conclusions:Within 24 h of HIBD modeling, the severity of brain injury can be preliminarily predicted by general condition score and Longa score. 4 weeks after modeling, in the chronic phase of brain injury, MRI was proved to be an excellent predictor for mid-term and long-term neurobehavioral abnormalities in HIBD rats.

Correlation between in-vivo mercury exposure from Cinnabaris and memory disorders in juvenile rat / 中国药科大学学报

@#Cinnabaris(α-HgS) is a mineral traditional Chinese material medica, as a tranquilizer and sedative, which is widely used in combination with herbs for the treatment of children high fever and convulsion.However, a large amount of mercury in Cinnabaris poses a potential risk to the immature central nervous system of children and probably causes severe memory disorders.Inthisstudy,three groups of juvenile rats were given low, medium, and high doses of Cinnabaris by oral gavage once a day for 14 continuous weeks, respectively.The blood mercury concentrations of the rats at different growth phases were monitored by atomic fluorescence spectrometry.The brain structural and functional changes related to the memory functions were investigated through HE staining and Morris water-maze test. Correlation analysis was conducted to clarify the dose- mercury exposure-toxic effect relationship of Cinnabaris and memory disorders.It was found thatthe blood mercury levels increased in both time- and dose-dependent manner.After the 14-week continuous administration of Cinnabaris, the pathological lesions in hippocampal neurons of rats in the high dose group were observed including pyknosis and disordered cell arrangement.In the Morris water-maze test, compared with the control group, rats in the high dose group exhibited the significantly prolonged latency to find the platform and the target quadrant, and the time spent in the target quadrant was obviously shortened. Thus, the significant correlations were established between Cinnabaris dose and mercury exposure,mercury exposure and memory disorders, respectively. In conclusion, the long-term and overdose administration of Cinnabaris in juvenile rats can increase the in-vivo mercury level, destroy the normal hippocampal morphological structure, and lead to memory disorders. This study provided scientific references for the potential mercury poisoning risks pharmacovigilance of Cinnabaris-containing paediatric formulations.

Octreotide-mediated neurofunctional recovery in rats following traumatic brain injury. Role of H2S, Nrf2 and TNF-α

ABSTRACT Purpose: To explore the role and mechanisms of octreotide in neurofunctional recovery in the traumatic brain injury (TBI) model. Methods: Rats were subjected to midline incision followed by TBI in the prefrontal cortex region. After 72 hours, the behavioural and neurological deficits tests were performed, which included memory testing on Morris water maze for 5 days. Octreotide (15 and 30 mg/kg i.p.) was administered 30 minutes before subjecting to TBI, and its administration was continued for three days. Results: In TBI-subjected rats, administration of octreotide restored on day 4 escape latency time (ELT) and increased the time spent in the target quadrant (TSTQ) on day 5, suggesting the improvement in learning and memory. It also increased the expression of H2S, Nrf2, and cystathionine-γ-lyase (CSE) in the prefrontal cortex, without any significant effect on cystathionine-β-synthase. Octreotide also decreased the TNF-α levels and neurological severity score. However, co-administration of CSE inhibitor (D,L-propargylglycine) abolished octreotide-mediated neurofunctional recovery, decreased the levels of H2S and Nrf2 and increased the levels of TNF-α. Conclusions: Octreotide improved the neurological functions in TBI-subjected rats, which may be due to up-regulation of H2S biosynthetic enzyme (CSE), levels of H2S and Nrf2 and down-regulation of neuroinflammation.

Protective effect of CD73 inhibitor α, ß-methylene ADP against amyloid-ß-induced cognitive impairment by inhibiting adenosine production in hippocampus

BACKGROUND: Alzheimer's disease (AD) is a chronic, progressive neurodegenerative disease. Recent studies have reported the close association between cognitive function in AD and purinergic receptors in the central nervous system. In the current study, we investigated the effect of CD73 inhibitor α, ß-methylene ADP (APCP) on cognitive impairment of AD in mice, and to explore the potential underlying mechanisms. RESULTS: We found that acute administration of Aß1­42 (i.c.v.) resulted in a significant increase in adenosine release by using microdialysis study. Chronic administration of APCP (10, 30 mg/kg) for 20 d obviously mitigated the spatial working memory impairment of Aß1­42-treated mice in both Morris water maze (MWM) test and Y-maze test. In addition, the extracellular adenosine production in the hippocampus was inhibited by APCP in Aß-treated mice. Further analyses indicated expression of acetyltransferase (ChAT) in hippocampus of mice of was significantly reduced, while acetylcholinesterase (AChE) expression increased, which compared to model group. We observed that APCP did not significantly alter the NLRP3 inflammasome activity in hippocampus, indicating that anti-central inflammation seems not to be involved in APCP effect. CONCLUSIONS: In conclusion, we report for the first time that inhibition of CD73 by APCP was able to protect against memory loss induced by Aß1­42 in mice, which may be due to the decrease of CD73-driven adenosine production in hippocampus. Enhancement of central cholinergic function of the central nervous system may also be involved in the effects of APCP.

The effect of moderate running wheel exercise on the learning and memory ability and hippocampal neurogenesis in young mice / 中华行为医学与脑科学杂志

Objective To observe the effect of moderate running wheel exercise on the learning and memory ability and hippocampal neurogenesis in young mice.Methods Twenty male 1 month old Kunming mice were randomly divided into control group and exercise group.After 8 weeks of running wheel exercise in the exercise group,the Morris water maze test was used to detect the spatial learning and memory ability of the two groups of mice.Immunohistochemical technique was used to detect the expression of Sox2,Ki67 and DCX in the dentate gyrus of mice in two groups,and those specific protein can reflected the hippocampal neurogenesis.Results In the place navigation test of Morris water maze,the latency of the exercise group ((29.00± 1.32) s) was lower than that of the control group ((36.30±0.69) s),and the difference was statistically significant (t=5.154,P＜0.05).In the spatial probe test,the number of times of crossing platforms in the exercise group ((3.73±1.51) times) was more than that of the control group ((1.89±t 1.63) times),and the difference was significant (t=3.583,P＜0.05).Immunohistochemical results showed that the number of Sox2,Ki67 and DCX immunoreactive cells in the dentate gyrus region of the exercise group were ((284.40± 31.50),(54.50± 10.75),(77.80=t± 11.60) respectively) more than those in the control group ((241.40± 10.57),(37.00± 7.81),(48.20±t 11.86) respectively),and the difference was statistically significant (t =4.129,5.789,7.971,all P＜0.01).Conclusion Moderate running wheel exercise can significantly improve the learning and memory ability of young mice,which may be related to the promotion of neurogenesis in the dentate gyrus of the hippocampus.

Effects of Angelica Polysaccharide on Learning and Memory Abilities and Aβ Metabolism in Model Rats with Alzheimer Disease / 中国中医药信息杂志

Objective To investigate effects of angelica polysaccharide on learning and memory abilities, Ach, ChAT, AChE, SOD, MDA in serum, APP and Aβ1-42 in hippocampus in model rats with Alzheimer disease (AD); To explore the mechanism of angelica polysaccharide for the treatment of AD. Methods Seventy SPF Wistar rats were selected for learning and memory ability by water maze. 10 rats were randomly selected (half female and half male) as sham-operation group, and the others were injected with Aβ25-35 by stereotatic techniques, copying AD model rats. 50 rats for learning and memory ability by water maze were successfully divided into model group, positive group, angelica polysaccharide low-, medium-, and high-dose groups, with 10 rats in each group. Rats in model group and sham-operation group were given normal saline for gavage, while rats in medication groups were given relevant medicine for gavage, 2 mL/(100 g?d), for 28 d. The learning and memory ability of rats in each group was tested by Morris water maze during 25-28 days, and the contents of Ach, ChAT, AChE, SOD, MDA in serum and APP and Aβ1-42 in hippocampus were determined. Results Compared with the sham-operation group, the escape latent period of model group was significantly prolonged in place navigation experiment; the target quadrant time was shortened; the latent time for the first time to reach the original escape platform was longer in spatial probe test; the residence time of crossing the original platform position and the target quadrant was shorter; the levels of Ach, the activity of ChAT and SOD in serum decreased; the levels of MDA, the activity of AChE in serum increased; the levels of APP and Aβ1-42 in hippocampus increased, with statistical significance (P<0.05, P<0.01). Compared with model group, the escape latent period of each medication group was shortened in different degrees after the intervention treatment; the residence time of target quadrant was prolonged; the latent time for the first time to reach the original escape platform was shortened; the number of cross platform increased; the levels of Ach, the activity of ChAT and SOD in serum increased; the levels of MDA and the activity of AChE in serum decreased; the levels of APP and Aβ1-42 in hippocampus significantly decreased, with statistical significance (P<0.05, P<0.01). Conclusion Angelica polysaccharide may effectively improve the learning and memory of ability of AD model rats to improve anti-free radical oxidation and promote Aβ metabolism and promote learning and memory ability of AD model rats, which have some preventive and therapeutic effects on AD.

Observation of β-amyloid plaques in retinas from live Alzheimer's model mice in different months / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To study the correlation of β-amyloid(Aβ)plaques in retinas from Alzheimer's model mice in different months and progression of disease. <p>METHODS: Six-month(<i>n</i>=6)and twelve-month(<i>n</i>=6)old Alzheimer's model mice, together with six-month(<i>n</i>=6)and twelve-month(<i>n</i>=6)old C57 mice were in this experiment. Morris water maze test was to assess the spatial memory. After intragastrical administration of curcumin for consecutive three days, the Aβ plaques in retinas(<i>n</i>=48)from all mice(<i>n</i>=24)were detected by noninvasive <i>in vivo</i> optical imaging. <p>RESULTS: Morris water maze test: compared with the six-month control group(C6), six-month model mice(AD6)swam longer(<i>P</i><0.05); and AD6 swam longer distance and experienced more crossing times than C6(<i>P</i>>0.05); compared with the twelve-month control group(C12), twelve-month model mice(AD12)swam longer, swam longer distance(<i>P</i><0.05)and experienced more crossing times(<i>P</i>>0.05); compared with the six-month model mice(AD6), twelve-month model mice(AD12)swam longer, swam longer distance and experienced more crossing times(<i>P</i><0.05). Moreover, the result of retinal Aβ plaques: We identified retinal Aβ plaques in postmortem from AD6 and AD12. Two six-month model mice had been detected retinal Aβ plaques, thus the positive rate of retinal Aβ plaques in six-month model mice was 33%; And six twelve-month model mice had been detected retinal Aβ plaques, thus the positive rate of retinal Aβ plaques in twelve-month model mice was 100%; Plaques were undetectable in age-matched non-AD individuals neither in six-month or in twelve-month; the positive rate of retinal Aβ plaques in AD12 was higher than AD6(<i>P</i><0.05). <p>CONCLUSION: Six-month model mice(AD6)had already a decline of cognition; and the illness gradually increased with the extension of the disease, and the positive rate of retinal Aβ plaques is increasing with progression of Alzheimer's disease.

Effect of 1,2-dichloroethane on learning and memory in NIH mice / 中国职业医学

OBJECTIVE: To investigate the effects of subacute systemic inhalation exposure of 1,2-dichloroethane(1,2-DCE) on learning and memory in NIH mice. METHODS: Forty-five specific pathogen free healthy 7-week-old NIH mice were randomly divided into control,low-dose and high-dose groups with 5 female mice and 10 male mice in each group. The mice were exposed to 1,2-DCE at dosages of 0. 00,100. 00 and 350. 00 mg/m3 for 6 hours per day for consecutive 28 days by dynamic systemic inhalation. The neurobehavioral tests of mice were performed before and after the first to fourth weeks of exposure using the Morris water maze test. RESULTS: There was no significant difference in body weight and swimming speed among the three groups of mice( P > 0. 05). The navigation experiment results showed that the escape latency of mice in both low-and high-dose groups were longer than that of the control group at the same time point(P < 0. 05) during 1-4 weeks after exposure. In the control group,the escape latency was shorter than that of the same group before exposure( P < 0. 05). The escape latency of high-dose group prolonged with the increase of exposure time,and in the 4 th week the escape latency was significantly higher than that of the same group before exposure( P < 0. 05).The experiment results of space exploration indicated that the first time of crossing platform in low-and high-dose groups were longer than that of the control group at the second to the fourth week( P < 0. 05). The target quadrant retention time and the number of crossing the platform in the low-and high-dose groups were lower than those in the control group( P <0. 05). CONCLUSION: Subacute inhalation exposure of 1,2-DCE can impair the learning and memory ability of NIH mice.The high-dose exposure may reduce learning ability in mice in a time-effect manner.

Comparison of the behavior characteristics in SHR, WKY and SD rat models of attention deficit/hyperactivity disorder / 中国实验动物学报

Objective To compare the differences in behavior characteristics among SHR, WKY and SD rat models of attention deficit/hyperactivity disorder (ADHD), and explore an ideal control model of SHR rats.Methods Using open field test to analyze the rat movement distance, speed, wearing numbers and the number of grooming to evaluate the spontaneous movement in SHR, WKY and SD rats.Using the Morris water maze to test the learning and memory ability among the three rat groups.Results The result of open field test showed that the SHR rats had significantly increased (P< 0.01) total amount of exercise, average speed and wearing numbers than WKY and SD rats.Compared with the WKY rats, SD rats had a significantly higher movement distance (P< 0.01), slightly higher movement speed and wearing number (P< 0.05).In the Morris water maze hidden platform period test, the SD rats had a significantly longer latency than the SHR rats (P< 0.05).SD rats showed longer latency distance on the first, third and fourth days of training, as compared with the SHR rats (P< 0.05 or P< 0.01).Compared with the WKY group, SD rats showed a shorter latency distance in each training time (P< 0.05 or P< 0.01).In the probe trial period, the SD rats showed shorter time and distance ratio to the target quadrant than SHR rats (P< 0.05), while significantly longer than the WKY rats (P< 0.05 or P< 0.01).Conclusions There are significant behavioral differences between SHR and WKY rats, showing certain disadvantages in comparison of the two types of rats.To add SD rats as a control group for SHR rats can improve the comparability of behavior characteristics of SHR rats, and to get more objective evaluation of the behavior characteristics of SHR rats.

Tetramethylpyrazine protects learning memory of hypoxichypoxia rats through interfering expression of GABA receptor and FOXP2 / 中国药理学通报

Aim To examine the influence of tetramethylpyrazine on learning and memory function of hypoxic hypoxia rats, and the expression of gamma aminobutyric acid(GABA) receptor and forkhead box P2(FOXP2) in hippocampus of rats.Methods A total of 120 Sprague Dawley rats were randomly divided into low hypoxic hypoxia and high hypoxic hypoxia groups, then according to different time points every group was divided into 1 d, 3 d, 7 d 15 d, 30 d group, with 12 rats per each group.Experiment group and the control group were treated with tetramethylpyrazine and 0.9% normal saline, respectively.The hypoxic hypoxia environment was achieved by putting the rats in a hypobaric chamber at a simulated altitude of 5 500 meters for different days.The capabilities of learning and memory of rats were detected by Morris water maze test.The expression of GABA receptor and FOXP2 protein in hippocampus of rat was determined by Western blot.Results ① Morris water maze test showed that the total distance of rats in the simulated hypobaric hypoxia control group was longer than that in the tetramethylpyrazine group(P0.05);however,GABAB1 receptor and FOXP2 protein rose from the third day(P<0.05).The expression of GABAAα1 receptor and FOXP2 protein expression were correlated to total distance of Morris water maze in the control group(r=-0.738, P<0.05;r=-0.693, P<0.05), and the expression of GABAB1 receptor was correlated with FOXP2 protein level(r=0.834, P<0.05).Conclusion The simulated high-altitude hypobaric hypoxia can decrease the learning and memory abilities of rats, which may be ameliorated by tetramethylpyrazine intervention, and this effect might be related to the increase of GABAB1R receptor and FOXP2 expression in hippocampus of rats.

Aβ25-35 protein in different concentrations to create a rat model resembling Alzheimer's disease and the differences in their learning and memory ability / 中国比较医学杂志

Objective To observe the learning and memory ability of rats after injection of Aβ25-35 protein in different concentrations into the lateral ventricle assessed by Morris water maze test, and to explore the optimal concentration of Aβ25-35 in the preparation of AD model rats.Methods Male SD rats were randomly divided into sham operated group and model group.The rats of model group received Aβ25-35 injection in concentrations of 2 μg/μL, 4 μg/μL and 8 μg/μL, respectively.According to the Rat Brain Stereotaxic Atlas, 5 μL of aggregation of Aβ25-35 was injected into the right lateral ventricle to establish the AD rat model.7 days after successful modeling, Morris water maze was used to test thechanges of learning and memory ability of the rats.Results There was no significant difference in the average swimming speed between the two groups (P > 0.05).The escape latency time of rats in the model group was significantly increasedcompared with the sham group (P 0.05).The activity time and distance of target quadrant of the rats injected with different concentration of Aβ25-35in the model group were significantly reduced compared with the sham group (P 0.05).Compared with the sham-operated group, the number of platform-crossing of rats injected with different doses of Aβ25-35in the model group were significantly reduced (P 0.05).Conclusions The recommended dose and concentration of Aβ25-35 to be injected into the unilateral ventricle to establisha rat model of Alzheimer's disease is 4 μg/μL in a volume of 5 μL.

Brain Cell Injuries and Behavioral Changes in Rats with Kernicterus / 中国康复理论与实践

@#Objective To study the brain cell injuries and behavioral changes of newborn rats with kernicterus. Methods Twenty-five 5-day-old Sprague-Dawley rats were divided into control group (n=11) and model group (n=14) radomly. The model group was injected with bilirubin solution 10 μg/g in the cisterna magna, while the control group was injected with equal volume of normal saline. The neurobehavioral changes were observed and the body mass were recorded. TUNEL staining was used to check the apoptosis of striatal nerve cells of basal ganglia in the model group (n=3) on the first day after modeling. The remaining rats were assessed by gait analysis and beam-walking test 19 days after birth, and Morris water maze test was performed 30 days after birth. Results The model group showed apparently abnormal neurobehavioral changes, such as clenched fists, opisthotonos and the body mass were significantly lower in the model group than in the control group (F>27.707, P<0.001). TUNEL staining showed striatal nerve cells apoptosis in the model group. For the gait analysis, the step lengths of both hind legs were shorter (t>4.129, P<0.01), and the difference of step length was longer (t=-4.415, P<0.001) in the model group than in the control group, however, there was no significantly difference in the step width between two groups (t=0.462, P=0.649). For the beam-walking test, the score was lower in the model group than in the control group (t=-3.644, P=0.004). For the Morris water maze test, the escape latency was longer (F>6.206, P<0.05), and the number of crossing platform was less (t=3.297, P=0.004) in the model group than in the control group. Conclusion The newborn rats' model of kernicterus showed deficits in multiple motor functions and learning and memory ability, which could be assessed by gait analysis, beam-walk test and Morris water maze test, respectively.

Effect of endoplasmic reticulum stress in the occurrence of Methotrexate-related neurotoxicity and cognitive impairment / 中华实用儿科临床杂志

Objective To investigate the relationship between Methotrexate (MTX) and its cognitive dysfunction,and to explore the possible mechanism of neurotoxicity induced by MTX.Methods Thirty healthy male SD rats weighting 180-220 g were divided into 3 groups using random number table:control group,60 mg/kg MTX (MTX60) group and 100 mg/kg MTX (MTXt00) group,with 10 rats in each group.The rats in MTX60 group,MTX100 group received 60 mg/kg MTX and 100 mg/kg MTX,respectively.The rats in control group accepted the same volume of 9 g/L saline injection as MTX group.Spatial memory of rats was evaluated by using Morris water maze test at different time points after pretreatment with MTX.After the Morris water maze test,the hippocampus were harvested and the expressions of C/EBP homologous protein (CHOP),cysteinyl aspartate specific proteinase 12(caspase-12) and cleave cysteinyl aspartate specific proteinase 3 (cleaved caspase-3) were detected by using Western blot.Meanwhile,cell apoptosis and pathological change of hippocampal neurons were detected by terminal dexynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) assay and HE staining respectively.Results In the Morris water maze test,the time in platform quadrant of rats in MTX60 group and MTX100 group was shorter than that of rats in control group during probe training [(27.30 ±3.98) s and (21.63 ±4.22) s vs (33.30 ±6.31) s,F =13.94,P ＜0.05],and the time in target quadrant of MTX100 group was shorter than that of MTX60 group (P ＜ 0.05).Compared with the control group,there were degenerated neurons in hippocampus cornu ammonis 1 (CA1) area in MTX60 group and MTX100 group.The number of TUNEL-positive cells of the hippocampus CA1 area increased significantly in MTX60 group and MTX100 group rats [(4.72 ±0.12)％ and (9.12±0.12)％ vs (1.11 ±0.49)％,F=95.272,P ＜0.05],and the TUNEL-positive cells of rats in MTX100 group were more than those of MTX60 group (P ＜ 0.05).The expressions of CHOP,caspase-12 and cleaved caspase-3 also increased compared with the control group (CHOP:2.98 ±0.31 and 4.15 ±0.61 vs 0.38 ±0.12,F =232.74,P ＜ 0.05;caspase-12:0.33 ±0.04 and 0.43 ±0.06 vs 0.14 ±0.02,F =120.70,P ＜ 0.05;cleaved caspase-3:0.35 ± 0.04 and 0.44 ± 0.06 vs 0.05 ± 0.03,F =198.64,P ＜ 0.05),and the protein expression levels of rats in MTX100 group were higher than MTX60 group (all P ＜ 0.05).Conclusions MTX can induce cognitive impairment in rats,and endoplasmic reticulum stress mediated hippocampal neurons apoptosis may play an important role in the mechanism of MTX-induced cognitive impairment in rats.

Enhancement of Short-Term Memory by Methyl-6-(Phenylethynyl)-Pyridine in the BTBR T+tf/J Mouse Model of Autism Spectrum Disorder

BACKGROUND: Autism spectrum disorder (ASD) encompasses a range of disorders that are characterized by social and communication deficits and repetitive behaviors. This study evaluated the effect of methyl-6-(phenylethynyl)-pyridine (MPEP), an antagonist of the mGluR5 metabotropic glutamate receptor, on memory enhancement in the BTBR T+tf/J (BTBR) mouse strain, which has been recognized as a model of ASD. METHODS: The pharmacological effects of MPEP on memory and motor coordination were assessed using the Morris water maze and rotarod tests in BTBR and C57BL/6J (B6) mice. Furthermore, we performed morphological analyses of cerebellar foliation in BTBR and B6 mice using hematoxylin and eosin staining. RESULTS: MPEP-treated BTBR mice exhibited improved learning and memory in the Morris water maze test. MPEP administration also improved motor coordination in the rotarod test. However, no significant difference was observed regarding the numbers of Purkinje cells in the cerebella of BTBR versus normal B6 mice. CONCLUSION: This study suggests that the mGluR5 antagonist MPEP has the potential to ameliorate learning and memory dysfunction and impaired motor coordination in BTBR mice. These results further suggest that the BTBR mouse model may be useful in pharmacological studies investigating drugs that could potentially alleviate cognitive dysfunction in ASD.

Improving effects of dammarane sapogenins on sleep interruption-induced learning and memory impairment in mice / 中国比较医学杂志

Objective To study the effects of dammarane sapogenins ( DS-1226 ) on sleep interruption-induced learning and memory impairment in mice.Methods 130 SPF healthy 5 -6-week old male ICR mice were randomly divided into control, model, DS-1226 low dose, DS-1226 medium dose and DS-1226 high dose groups.The behavioral alterations in open field (OF), Morris water maze (MWM) and step-through (ST) tests were detected at 15 days after rotating drum-induced sleep interruption ( SI) .Results The total distance, movement speed, total duration of movement were increased in OF test ( P<0.05, vs.the model group) after treatment.The latency of place navigation was increased from day 5 in the MWM test after 15 d sleep interruption, and the number of crossing in the target quadrant and the percent distance in target quadrant were decreased after 15 d sleep interruption ( P <0.05, vs.the control group), while the latency of place navigation was decreased, and the percent distance in target quadrant and percent time in target quadrant after high dose DS-1226 oral administration ( P<0.05, vs.the model group) were increased.Error times, distance in dark chamber, time in dark chamber and immobility time in dark chamber were increased in training of step through test ( P<0.05, vs.the control group);while these indexes were decreased after DS-1226 oral administration ( P<0.05, vs.the model group) .But there was no significant difference in the step through testing course.Conclusions The results show that orally administrated DS-1226 can ameliorate SI-induced learning and memory impairment, and there is a significant dosage-effect relationship.

Behavioral differences in learning and memory abilities among three animal models of Alzheimer′s disease assessed by Morris water maze test / 医学研究生学报

Objective The study was to evaluate the behavioral differences in learning and memory abilities among three ani -mal models of Alzheimer′s disease. Methods Three SD rat models(n=20) were used in this study.The first SD rat model was es-tablished by intracerebral injection of Aβ25-35 into the bilateral hippocampus , the second mouse model was induced by intraperitoneal in-jection of scopolamine and the third was a senescence accelerated mouse model .Morris Water maze test was performed to investigate behavioral differences by comparison to corresponding blank control groups ( sham operation group , blank group and P8 group ) . Results The learning and memory abilities of senescence accelerated rats and scopolamine -treated rats were worse than those of the corresponding control groups, especially the scopolamine-treated rat ([35.47 ±3.78]s vs [50.61 ±3.94]s, P0.05). Conclusion The model of Alzheimer′s disease in-duced by intraperitoneal injection of scopolamine represents more distinct changes in learning and memory abilities .Morris water maze test can be used to well evaluate whether the scopolamine-induced model is successfully established or not .

Effects of chronic restraint stress on learning and memory in SD and Wistar rats / 中国实验动物学报

Objective To investigate the effects of chronic restraint stress on learning and memory in Wistar and Sprague-Dawley (SD) rats.Methods Healthy adult male Wistar rats (n=6) and Sprague-Dawley rats (n=6) were subjected to restraint stress 10 h daily for 28 days.After that, all rats were tested for recognition memory by novel object recognition test , and spatial memory and working memory by Morris water maze test .Results After restraint for 10 h daily for 28 days, the restraint rats of the two strains demonstrated lower discrimination index (DI)than the control group, but on-ly SD rats showed significant difference ( P<0.05 ) .The restraint SD rats showed higher escape latency than the control rats, and on the 5th day the difference became significant (P<0.05), and there was no significant difference between Wistar restraint and control rats .The working memory test showed that restraint SD rats exibited longer escape latency than the control rats (P<0.05), while Wistar rats didn’t show significant difference between the two groups .Conclusions The results of this study demonstrate that the impairments of learning and memory in SD rats subjected to restraint 10 hour per day for 28 days are more serious than that in the Wistar rats .Therefore , SD rats may be a better choice as an animal model to study the effects of chronic restraint stress on learning and memory impairment .

Effects of high protein feeding on brain's myelination and learning ability of intrauterine grow retardation in rats / 中华实用儿科临床杂志

Objective To explore the influence of 300 g/kg high protein diet on myelination of the intrauterine grow retardation (IUGR) in the rat brain and their learning and memory ability.Methods The pregnant rats were fed with 60 g/kg low protein diet.After birth,the offspring of IUGR group were fed separately by 300 g/kg high-protein diet (SH group) and 210 g/kg normal-protein diet(SC group).Forty newborn female pups,born from pregnant rats fed by normal-protein diet,were used as the control group(CC group).On the first,the 7th,the 15th and the 218t day,the body weight,brain weight of the offspring and their dynamics expressions of myelin basic protein(MBP) in corpus callosum,internal capsule and external capsule were observed with immunohistochemistry method.Morris water maze test was performed to assess learning and memory ability during the 26th-32ed,then the expression of MBP in the brain was observed.Results On the 21st day,the SH group gained catch-up growth weight,while the brain weight of them was still lower than that of the CC group (P ＜ 0.05),but higher than that of the SC group.At each time point,the MBP expression in corpus callosum,internal capsule and external capsule of SH group and SC group was lower than that of the CC group(all P ＜0.05),whereas the expression of myelin basic protein in the SH group was higher than that in SC group.The average latencies in all rats were reduced to some degree from the first to the 5th day.On the 5th day,there was no significantly difference between the SH group and CC group (P ＞ 0.05),while the escape latency was significantly shorter in rats of SH group than those of SC group (P ＜ 0.05).As far as search strategy was concerned,there was no difference in SH group and SC group of rats(P ＞ 0.05),but they performed better than those in the SC group on the 5th day(P ＜0.05).The frequency of passing through the platform quadrant was not significantly difference in rats among the 3 groups (P ＞ 0.05).Conclusions 300 g/kg high-protein diet on IUGR rats can increase brain weight and the expression of MBP,and improve the ability of learning to some extend.

Effect of Codonopsis lanceolata with Steamed and Fermented Process on Scopolamine-Induced Memory Impairment in Mice

Codonopsis lanceolata (Campanulaceae) traditionally have been used as a tonic and to treat patients with lung abscesses. Recently, it was proposed that the extract and some compounds isolated from C. lanceolata reversed scopolamine-induced memory and learning deficits. The purpose of this study was to evaluate the improvement of cognitive enhancing effect of C. lanceolata by steam and fermentation process in scopolamine-induced memory impairment mice models by passive avoidance test and Morris water maze test. The extract of C. lanceolata or the extract of steamed and fermented C. lanceolata (SFCE) was orally administered to male mice at the doses of 100 and 300 mg/kg body weight. As a result, mice treated with steamed and fermented C. lanceolata extract (SFCE) (300 mg/kg body weight, p.o.) showed shorter escape latencies than those with C. lanceolata extract or the scopolamine-administered group in Morris water maze test. Also, it exerted longer step-through latency time than scopolamine treated group in passive avoidance test. Furthermore, neuroprotective effect of SFCE on glutamate-induced cytotoxicity was assessed in HT22 cells. Only SFCE-treated cells showed significant protection at 500 microg/ml. Interestingly, steamed C. lanceolata with fermentation contained more phenolic acid including gallic acid and vanillic acid than original C. lanceolata. Collectively, these results suggest that steam and fermentation process of C. lanceolata increased cognitive enhancing activity related to the memory processes and neuroprotective effect than original C. lanceolata.

Comparative Study of the Effects of Different Growth Hormone Doses on Growth and Spatial Performance of Hypophysectomized Rats

This study was designed to examine the effects of recombinant human growth hormone replacement on somatic growth and cognitive function in hypophysectomized (HYPOX) female Sprague-Dawley rats. Rats (5 per group) were randomized by weight to 3 experimental groups: group 1, administered 200 microgram/kg of GH once daily for 9 days; group 2, administered 200 microgram/kg of GH twice daily; and group 3, administered saline daily. Somatic growth was evaluated by measurement of body weight daily and of the width of the proximal tibial growth plate of the HYPOX rats. Cognitive function was evaluated using the Morris water maze (MWM) test. The results indicated that GH replacement therapy in HYPOX rats promoted an increase in the body weight and the width of the tibial growth plate in a dose-dependent manner. On the third day of the MWM test, the escape latency in the GH-treated groups 1 and 2 was significantly shorter than that in the control rats (P<0.001 and P=0.032, respectively), suggesting that rhGH improved spatial memory acquisition in the MWM test. Therefore it is concluded that rhGH replacement therapy in HYPOX rats stimulates an increase in somatic growth in a dose-dependent manner and also has beneficial effects on cognitive functions.