Effects of subchronic exposure to benzoɑpyrene on memory function and mRNA expressions of NMDA receptors in different brain regions in rats / 环境与职业医学

Background The altered expressions of hippocampal N-methyl-D-aspartate (NMDA) receptors induced by benzo[ɑ]pyrene (BaP) causes short-term spatial learning and memory impairment in humans and animals, but whether BaP causes alterations of NMDA receptor subunits in other brain regions and the associated neurotoxic mechanism is still essentially unknown. Objective To observe the mRNA expressions of NR1, NR2A, and NR2B of NMDA receptor subunits in different brain regions in SD rat model with subchronic exposure to BaP, and to provide a basis for in-depth study of the mechanism of BaP-induced neurotoxicity. Methods Forty male SD rats were selected and randomly divided into a control group and 1.00, 2.50, and 6.25 mg·kg−1 BaP exposure groups with 10 rats in each group. The exposure rats received intraperitoneal injection of BaP every other day for 90 d.The average latency to platform, the average total distance, and the duration spent in previous quadrant were measured by the Morris Water Maze. Real-time fluorescence quantitative PCR was used to detect the mRNA expressions of NR1, NR2A, and NR2B in hippocampus, cortex, cerebellum, and striatum of rats. Results The average latency to platform and the average total distance in the 2.50 and 6.25 mg·kg−1 BaP groups were significantly prolonged compared with the control group (P<0.05), and the duration that rats spent in previous quadrant in the 6.25 mg·kg−1 BaP group was significantly shortened (P<0.05). Compared with the control group, the mRNA expressions of NR1 and NR2B in the hippocampus in the 2.50 and 6.25 mg·kg−1 BaP groups were significantly reduced (P<0.05), and the NR2A mRNA expression in the hippocampus in the 6.25 mg·kg−1 BaP group was significantly reduced (P<0.05); the mRNA expressions of NR1 and NR2B in the cortical tissue in the 6.25 mg·kg−1 BaP group were significantly reduced (P<0.05), and the mRNA expression of NR2A in the cortical tissue in the 1.00 mg·kg−1 BaP group was reduced; the mRNA expression of NR2B in the cerebellar tissue in the 6.25 mg·kg−1 BaP group was significantly reduced (P<0.05); there were no differences in the mRNA expressions of NMDA receptor subunits in the striatum tissue (P>0.05). Conclusion Subchronic BaP exposure can cause short-term spatial learning and memory impairment in rats, which may be related to the down-regulation of mRNA expressions of NR1, NR2A, and NR2B in hippocampus, changes of mRNA expressions of NR1, NR2A, and NR2B in cortical area, and the down-regulation of NR2B mRNA expression in cerebellum.

Effect of astragaloside IV on improvement of spatial learning and memory abilities and its mechanism in vascular dementia rat models of chronic cerebral ischemia / 中华神经医学杂志

Objective:To investigate whether astragaloside (AST) IV can improve spatial learning and memory abilities by alleviating oxidative stress damage to the frontal cortex and hippocampus in vascular dementia (VD) rats induced by chronic cerebral ischemia.Methods:Totally, 72 adult male Wistar rats were randomly assigned to four groups: sham-operated group ( n=12), model group ( n=20), AST-IV 10 mg group ( n=20), and AST-IV 20 mg group ( n=20); chronic cerebral ischemia-induced VD models in the later three groups were established by permanent bilateral common carotid artery occlusion (BCCAO); 3 h after BCCAO, these rats were administered with saline, 10 mg/kg AST-IV, or 20 mg/kg AST-IV once daily for a consecutive 90 d. Ninety-four d after modeling, spatial learning and memory abilities were assessed by Morris water maze; the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), and malondialdehyde (MDA) levels were measured by enzyme linked immunosorbent assay (ELISA). The levels of lipid peroxidation and oxidative DNA damage were assessed by immunohistochemical staining for 4-hydroxynonenal (4-HNE) and 8-hydroxy20-deoxyguanosine (8-OhdG), respectively. Results:(1) On the 3 rd, 4 th and 5 th d of place navigation test, the escape latency in rats of the model group was significantly longer than that in the sham-operated group, and that in the AST-IV 20 mg group was significantly shorter than that in the model group ( P<0.05); spatial probe test showed that the time percentage of rats spending in platform region in the model group (20.3%±1.7%) was significantly smaller than that in the sham-oprated group (48.2%±3.6%), and that in the AST-IV 20 mg group (39.7%±3.2%) was significantly larger than that in the model group ( P<0.05). (2) As compared with those in the sham-operated group, the SOD, GSH-Px and CAT activities were statistically decreased while MDA level was significantly increased in the frontal cortex and hippocampal CA1 area of rats in the model group ( P<0.05); as compared with those in the model group, the SOD, GSH-Px and CAT activities were statistically increased while MDA level was significantly decreased in the frontal cortex and hippocampal CA1 area of rats in the AST-IV 20 mg group ( P<0.05). (3) As compared with those in the model group, the numbers of 4-HNE and 8-oHdG positive cells in the frontal cortex and hippocampal CA1 area of rats in the AST-IV 20 mg group were significantly smaller ( P<0.05). Conclusion:Intraperitoneal injection of high dose AST-IV can ameliorate oxidative damage in the frontal cortex and hippocampal CA1 area in chronic cerebral ischemia-induced VD models, and has the potential to reverse spatial learning damages and memory dysfunction.

Comparative Study of ROCK1 and ROCK2 in Hippocampal Spine Formation and Synaptic Function / 神经科学通报·英文版

Rho-associated kinases (ROCKs) are serine-threonine protein kinases that act downstream of small Rho GTPases to regulate the dynamics of the actin cytoskeleton. Two ROCK isoforms (ROCK1 and ROCK2) are expressed in the mammalian central nervous system. Although ROCK activity has been implicated in synapse formation, whether the distinct ROCK isoforms have different roles in synapse formation and function in vivo is not clear. Here, we used a genetic approach to address this long-standing question. Both Rock1 and Rock2 mice had impaired glutamatergic transmission, reduced spine density, and fewer excitatory synapses in hippocampal CA1 pyramidal neurons. In addition, both Rock1 and Rock2 mice showed deficits in long-term potentiation at hippocampal CA1 synapses and were impaired in spatial learning and memory based on the water maze and contextual fear conditioning tests. However, the spine morphology of CA1 pyramidal neurons was altered only in Rock2 but not Rock1 mice. In this study we compared the roles of ROCK1 and ROCK2 in synapse formation and function in vivo for the first time. Our results provide a better understanding of the functions of distinct ROCK isoforms in synapse formation and function.

Expression of neuronal migration-related factors and the spatial learning and memory of rats prenatally exposed to tritiated water / 中华放射医学与防护杂志

Objective@#To study the expression of neuronal migration-related factors and spatial learning and memory of rats exposed to tritiated water (HTO).@*Methods@#Hippocampal neural cells from newborn Sprague-Dawley(SD) rats at postnatal 24 h were primarily cultured in DMEM/F12 medium with 20% of fetal bovine serum for 6 days, followed by subjection to tritiated water(HTO) at concentrations of 3.7×102, 3.7×103, 3.7×104, 3.7×105, 3.7×106 Bq/ml for 24 h, respectively. Western blot and RT-qPCR were used to determine the expression levels of F-actin, α-tubulin, tau, AP2, BDNF mRNA and Reelin mRNA. 16 pregnant SD rats at embryonic (E) day 14 were randomly divided into the tested and control groups (8 rats/ each group). The tested rats were injected with body fluid of HTO (3.7×106 Bq/g) intraperitoneally, while the saline as the control. Morris water maze (MWM) was employed for the spatial learning and memory of rats.@*Results@#Compared to the control cells, HTO caused a significant downregulation of expressions of cytoskeletal proteins [F-actin (t=8.898-19.896, P<0.05), α-tubulin (t=3.261-7.900, P<0.05), tau (t=2.274-5.003, P<0.05), and MAP2 (t=2.274-5.003, P<0.05)] and mRNA of BDNF(t=3.580-19.792, P<0.05) and Reelin (t=3.240-39.692, P<0.05) in the tested neural cells in a dose-dependent manner. In addition, the escape latency of irradiated offsprings was significantly prolonged (t=-2.563, P<0.05), the time for offsprings to cross through target quadrant was markedly reduced (t=3.214, P<0.05), and the swimming time in the platform quadrant of irradiated offsprings were obviously shortened (t=3.874, P<0.05) in the MWM trial.@*Conclusions@#The results indicate that HTO irradiation in utero downregulates the expressions of neuron migration-related factors and induces brain dysfunction, which may shed a light on a mechanism of the radiation-induced brain impairment.

Expression of neuronal migration-related factors and the spatial learning and memory of rats prenatally exposed to tritiated water / 中华放射医学与防护杂志

Objective To study the expression of neuronal migration-related factors and spatial learning and memory of rats exposed to tritiated water (HTO).Methods Hippocampal neural cells from newborn Sprague-Dawley (SD) rats at postnatal 24 h were primarily cultured in DMEM/F12 medium with 20％ of fetal bovine serum for 6 days,followed by subjection to tritiated water (HTO) at concentrations of 3.7× 102,3.7×103,3.7 × 104,3.7 × 105,3.7× 106 Bq/ml for 24 h,respectively.Western blot and RT-qPCR were used to determine the expression levels of F-actin,α-tubulin,tau,AP2,BDNF mRNA and Reelin mRNA.16 pregnant SD rats at embryonic (E) day 14 were randomly divided into the tested and control groups (8 rats/ each group).The tested rats were injected with body fluid of HTO (3.7× 106 Bq/g) intraperitoneally,while the saline as the control.Morris water maze (MWM) was employed for the spatial learning and memory of rats.Results Compared to the control cells,HTO caused a significant downregulation of expressions of cytoskeletal proteins [F-actin (t =8.898-19.896,P＜ 0.05),α-tubulin (t=3.261-7.900,P＜0.05),tau (t=2.274-5.003,P＜0.05),and MAP2 (t=2.274-5.003,P＜0.05)] and mRNA of BDNF (t=3.580-19.792,P＜0.05) and Reelin (t=3.240-39.692,P＜0.05)in the tested neural cells in a dose-dependent manner.In addition,the escape latency of irradiated offsprings was significantly prolonged (t =-2.563,P＜0.05),the time for offsprings to cross through target quadrant was markedly reduced (t=3.214,P＜0.05),and the swimming time in the platform quadrant of irradiated offsprings were obviously shortened (t =3.874,P＜0.05) in the MWM trial.Conclusions The results indicate that HTO irradiation in utero downregulates the expressions of neuron migration-related factors and induces brain dysfunction,which may shed a light on a mechanism of the radiation-induced brain impairment.

Small-scale environmental enrichment and exercise enhance learning and spatial memory of Carassius auratus, and increase cell proliferation in the telencephalon: an exploratory study

Carassius auratus is a teleost fish that has been largely used in behavioral studies. However, little is known about potential environmental influences on its performance of learning and memory tasks. Here, we investigated this question in C. auratus, and searched for potential correlation between exercise and visuospatial enrichment with the total number of telencephalic glia and neurons. To that end, males and females were housed for 183 days in either an enriched (EE) or impoverished environment (IE) aquarium. EE contained toys, natural plants, and a 12-hour/day water stream for voluntary exercise, whereas the IE had none of the above. A third plus-maze aquarium was used for spatial and object recognition tests. Different visual clues in 2 of its 4 arms were used to guide fish to reach the criteria to complete the task. The test consisted of 30 sessions and was concluded when each animal performed three consecutive correct choices or seven alternated, each ten trials. Learning rates revealed significant differences between EE and IE fish. The optical fractionator was used to estimate the total number of telencephalic cells that were stained with cresyl violet. On average, the total number of cells in the subjects from EE was higher than those from subjects maintained in IE (P=0.0202). We suggest that environmental enrichment significantly influenced goldfish spatial learning and memory abilities, and this may be associated with an increase in the total number of telencephalic cells.

Spatial Learning and Memory Using a Radial Arm Maze with a Head-Mounted Display

OBJECTIVE: A radial arm maze (RAM) is an essential tool for assessing spatial learning and memory. Although this tool is widely used to study deficits in spatial memory in animal models, it has several restrictions that prevent its adaptation to human research and training. Therefore, we developed a head-mounted-display RAM (HMD-RAM) program for humans and verified its validity by comparing it to the results obtained by previous RAM studies. We also compared the HMD and a flat monitor as experimental devices. METHODS: Forty participants were recruited for the current study (Study 1: 20 participants with the HMD device; Study 2: 20 participants with the flat monitor). They navigated a virtual room as a first-person viewer and used environmental landmarks to remember their spatial position and orientation. The main dependent measures were working memory error, reference memory error, detection time, travel distance, and participant’s head movements. To validate the program, participants also conducted neuropsychological assessments and self-reported measures. RESULTS: The results for HMD-RAM tasks were consistent with the results of previous research conducted on animals, and the HMD elicited a higher sense of presence, immersion, and simulator sickness than the flat monitor. According to post-experiment questions on navigation strategy, creating landmarks was important when people were discovering locations in their environment, and an HMD was beneficial for better navigation strategy. CONCLUSION: These results suggest that the HMD-RAM is valuable for estimating spatial learning and memory in humans and may be a useful tool for early diagnosis of deficits in spatial learning and memory, including amnestic mild cognitive impairment and Alzheimer’s disease.

Comparison of the cognitive function in rats at different brain developmental stages / 中国实验动物学报

Objective To investigate the relationship between different brain developmental stages and changes of cognitive function in rats. Methods 1-month, 2-month and 8-month-old rats were selected to imitate the juvenile, adolescent and adulthood, respectively, and their behavioral functions were compared. The reward operant conditioning and Morris water maze task were used to investigate the differences in exploration interest, executive and recognition ability, spatial learning and memory of the rats at different ages. Results In the reward operant conditioning and Morris water maze task, there was no significant difference in the cognitive function between 1-month and 2-month-old rats. In the reward conditioning phase, the nose pokes numbers of 8-month-old rats were significantly decreased compared with the 1-month-old rats (P＜ 0. 01). There was no significant difference in nose pokes accuracy. During the operant conditioning phase, the lever press numbers and accuracy of 8-month-old rats were significantly decreased ( P ＜ 0. 05 or P ＜ 0. 01) and the press latency was longer (P ＜ 0. 05). At the phase of visual identification, the press and reward numbers, and the visual identification index were significantly decreased ( P ＜ 0. 05 or P ＜ 0. 01). In the Morris water maze test, compared with the 1-month-old rats, the total swimming distance and escape latency of the 8-month-old rats were significantly increased (P＜ 0. 05), as well as average swimming speed ( P ＜ 0. 05 or P ＜ 0. 01) in spatial learning phage. In spatial memory phage, the swimming distance and time spent in the target quadrant were obviously decreased (P＜ 0. 01). Conclusions The cognitive functions of rats at different brain developmental stages are different. The juvenile and adolescent rats have similar cognitive functions, but 8-month-old adult rats appear decline in the exploration interest, executive and recognition ability, and spatial learning and memory function.

Effects of chronic restraint stress on abilities of spatial learning and memory and levels of excitatory amino acids in hippocampal dentate gyrus in old rats / 吉林大学学报(医学版)

Objective: To explore the effects of chronic restraint stress (CRS) on the abilities of spatial learning and memory and the levels of excitatory amino acids in the hippocampal dentate gyrus (DG) in the old rats, and to investigate the neurochemical mechanism of CRS in affecting the spatial learning and memory abilities. Methods: Sixteen male SD rats (18 months old) were randomly divided into control group (n=8) and CRS group (n=8), and the rats in CRS group received CRS 2 h every day for 30 d. And then the spatial learning and memory abilities of rats were measured by Morris water maze (MWM) test, and the extracellular levels of excitatory amino acids including asparate (Asp) and glutamate (Glu) in the DG were simultaneously determined by in vivo microdialysis and HPLC. The levels of corticosterone (CORT) and epinephrine (EPI) in serum of the rats were examined by ELISA assay. Results: In CRS group, the escape latencies on the 2nd-4th days were significantly increased and the percentage of time spent in target quadrant on the 5th day was markedly decreased in MWM test compared with control group (P0. 05). Compared with control group, the levels of CORT and EPI in the serum of the rats in CRS group were significantly increased (P<0. 05). Conclusion: CRS impairs the spatial learning and memory abilities in the old rats, which may be related to the decrease of Asp level in the hippicampal DG of the rats.

Effect of Jin's 3-needling therapy on executive function and spatial learning and memory abilities of frontal lobe injury rats / 中华神经医学杂志

Objective To investigate the effect of Jin's 3-needling therapy on executive function and spatial learning and memory abilities and their mechanism in frontal lobe injury rats. Methods Thirty-two male Sprague-Dawley rats were randomly divided into sham-operated group, Jin's 3-needling group, model group and medoba treatment group (n=8). The rats in the sham-operated group only underwent craniotomy to remove the bone flap and no impact was performed on the frontal lobe; the frontal lobe injury models of model group, Jin's 3-needling group and medoba treatment group were established by eCCI-6.3 device; rats in the Jin's 3-needling group were treated with Jin's 3-needling therapy, and rats in the madopa treatment group were given 2 mL of madopa suspension by perfusion once daily. The behavior of rats in each group was evaluated by GO/NO GO task and Morris water maze test, and apoptosis of cells was detected by TUNEL, dopamine receptor D1 (DRD1) expression was determined by immunohistochemistry, and the content of dopamine in frontal tissues was analyzed by high performance liquid chromatography. Results The accuracy rate of GO/NO GO task in Jin's 3 needling group was significantly higher than that in madopa treatment group (P<0.05); and that in madopa treatment group was significantly higher than that in model group (P<0.05). On the 3rd and 4th d of place navigation test, the escape latency in the Jin's 3 needling group and madopa treatment group was significantly decreased as compared with that in the model group (P<0.05); the escape latency in the Jin's 3 needling group was significantly decreased as compared with that in the madopa treatment group (P<0.05). In spatial probe test, the number of times of crossing the platform in the Jin's 3 needling group and madopa treatment group was significantly larger as compared with that in the model group (P<0.05). As compared with those in the model group, the number of apoptotic neurons in the frontal lobes was significantly larger, the content of dopamine in the frontal lobes and the DRD1 expression were significantly increased in the madopa treatment group and Jin's 3-needling group (P<0.05); the number of apoptotic neurons in the Jin's 3 needling group was significantly smaller as compared with that in the madopa treatment group (P<0.05); the content of dopamine in the frontal lobes and the DRD1 expression in the Jin's 3 needling group were significantly increased as compared with those in the madopa treatment group (P<0.05). Conclusion Jin's 3-needling therapy can effectively improve the executive function and spatial learning and memory abilities of frontal lobe damaged rats, and their mechanism may be related to decreased apoptosis of frontal tissue cells and increased dopamine content and increased DRD1 expression.

Effects of chronic restraint stress on abilities of spatial learning and memory and levels of excitatory amino acids in hippocampal dentate gyrus in old rats / 吉林大学学报(医学版)

Objective:To explore the effects of chronic restraint stress (CRS) on the abilities of spatial learning and memory and the levels of excitatory amino acids in the hippocampal dentate gyrus (DG) in the old rats,and to investigate the neurochemical mechanism of CRS in affecting the spatial learning and memory abilities.Methods:Sixteen male SD rats (18 months old) were randomly divided into control group (n =8) and CRS group (n=8),and the rats in CRS group received CRS 2 h every day for 30 d.And then the spatial learning and memory abilities of rats were measured by Morris water maze (MWM) test,and the extracellular levels of excitatory amino acids including asparate (Asp) and glutamate (Glu) in the DG were simultaneously determined by in vivo microdialysis and HPLC.The levels of corticosterone (CORT) and epinephrine (EPI) in serum of the rats wereexamined by ELISA assay.Results:In CRS group,the escape latencies on the 2nd-4th days were significantly increased and the percentage of time spent in target quadrant on the 5th day was markedly decreased in MWM test compared with control group (P＜0.05).Compared with before training,the extracelluar level of Asp in the DG in control group was significantly increased on the 2nd day in MWM test;compared with control group,the extracelluar level of Asp in the DG in CRS group was significantly decreased on the 3rd day in MWM test (P＜0.05).Compared with before training,the Glu levels in the DG in MWM test in both control and CRS groups were markedly increased (P＜0.05),but there was no significant difference between two groups (P＞0.05).Compared with control group,the levels of CORT and EPI in the serum of the rats in CRS group were significantly increased (P＜0.05).Conclusion:CRS impairs the spatial learning and memory abilities in the old rats,which may be related to the decrease of Asp level in the hippicampal DG of the rats.

Effects of Abnormal Phlegmatic Munziq on Ability of Learning and Memory and Protein Expressions of Brain Tissue RAGE and LRP1 of APP/PS1 Transgenic Mice Model of AD / 中国中医药信息杂志

Objective To investigate the effects of Abnormal Phlegmatic Munziq on ability of learning and memory, and protein expressions of brain tissue RAGE and LRP1 of APP/PS1 transgenetic mice model of AD;To discuss its mechanism of action. Methods Three-month-old APP/PS1 transgenic mice were randomly divided into 5 groups: model control group, positive control group, Abnormal Phlegmatic Munziq high-, medium-, and low-dose groups, 18 mice in each group. Another 18 three-month-old C57BL/6J mice were chosen as normal control group. All administration groups received relevant medicine for successive 6 months. Then the changes in ability of learning and memory of mice were detected by Step-down test; protein expressions of LRP1 and RAGE were detected by immunohistochemistry and Western blot. Results Compared with the normal control group, the reaction time of learning grades and the mistake times increased, incubation of memory grades decreased and the mistake times increased in the model control group (P<0.01);Compared with the model control group, the reaction time of learning grades and the mistake times decreased, incubation of memory grades increased and the mistake times decreased in all administration groups (P<0.05, P<0.01). Immunohistochemistry and Western blot results showed that compared with normal control group, the LRP1 expression decreased and RAGE increased in the model control group (P<0.05);Compared with the model control group, the LRP1 expression decreased and RAGE increased in Abnormal Phlegmatic Munziq high-, medium-, and low-dose groups (P<0.05,P<0.01). Conclusion Abnormal Phlegmatic Munziq can improve ability of spatial learning and memory in APP/PS1 mice and regulate the expressions of RAGE and LRP1.

Effect of Icariside Ⅱ on spatial learning and memory impairments and axonal regeneration in rats induced by chronic cerebral hypoperfusion / 中华行为医学与脑科学杂志

Objective To observe the effect of IcarisideⅡ (ICSⅡ) on spatial learning and memory impairments and axonal regeneration induced by chronic cerebral hypoperfusion (CCH) in rats.Methods 90 male SD rats were randomly divided into normal group,sham operation group,CCH group and ICS Ⅱ low,middle and high-dose treatment groups.The chronic cerebral hypoperfusion model was established by permanent bilateral common carotid artery occlusion.Then these rats in ICS Ⅱ low,middle and high-dose treatment groups were given ICS Ⅱ4,8 and 16 mg/(kg · d) by gavage on the 1st day after modeling.There were 5 rats in every group at each observing time(4,8 and 12 week).Morris water maze experiment was utilized to assess the escape latency and the target quadrant residence time while HE and immunohistochemistry analysis were applied to test the morphology change and expressions of GAP-43,MAP-2 and Nogo-A in hippocampal CA 1.Results Compared with those of sham operation groups at 4,8 and 12 week respectively,the escape latency in CCH group were significantly prolonged(40.02±4.95) s,(42.29±5.75) s,(53.68±6.14) s vs (26.43±2.68) s,(26.84±2.06) s,(31.53±4.12) s,P＜0.05;the target quadrant residence time were significantly reduced(28.53±2.40) s,(28.02±4.28) s,(22.60±4.03) s vs (33.34±2.89) s,(33.31 ±4.14) s,(31.63±2.20)s,P＜0.05);the expressions of GAP-43 and Nogo-A were increased with that of MAP-2 reduced(P＜0.05).Meanwhile,the neuropathological changes with more denatured neurons and less normal neurons were found in hippocampal CA1.However,compared with those of CCH group,the escape latency of ICS Ⅱ middle and high-dose groups (30.58±3.03) s,(29.19±4.23) s,(38.77±5.80) s;(28.90±2.98) s,(26.91 ±6.63) s,(36.51 ±3.98) s) were shortened (P＜0.05);the target quadrant residence time (32.54± 3.41) s,(32.69±3.47) s,(28.27±3.57) s;(32.69±3.54) s,(33.20±4.29) s,(28.07±4.04) s) were increased (P＜ 0.05);the expression of Nogo-A was decreased while those of GAP-43 and MAP-2 were conversely increased (P＜0.05).Moreover,few denatured neurons were observed in hippocampal CA1.But there were no differences for those indexs between CCH group and ICS Ⅱ low-dose treatment groups (P＞0.05).Compared with those in 8 week and 4 week,the escape latency and the target quadrant residence time were prolonged and reduced with the expression of Nogo-A increased in all groups except normal group and sham operation group(P＜0.05),the expressions of GAP-43 and MAP-2 were decreased in CCH group and ICS Ⅱ low-dose treatment group(P＜0.05),but there were no significant differences in ICS Ⅱ middle and high-dose treatment groups at 12 week(P＞0.05).However,there were no statistical significance of all indexes between 8 week and 4 week(P＞0.05).Conclusion ICS Ⅱ can improve the spatial learning and memory in chronic cerebral hypoperfusion rats,which may be achieved by neuroprotective effects and reducing the expression of Nogo-A consequently promotes the regeneration of axons.

Effects of Abnormal Phlegmatic Temperament Granules on Behavioristics and Hippocampus Pathomorphism of APP/PS1 Transgenic Mice / 中国中医药信息杂志

Objective To investigate the effects of Abnormal Phlegmatic Temperament Granules on spatial learning and memory, histopathology morphological change in hippocampus CA1 zone; To discuss its mechanism of action.Methods Three-month-old APP/PS1 transgenic mice were randomly divided into 5 groups: model control group, positive control (donepezil 0.92 mg/kg) group, Abnormal Phlegmatic Temperament Granules high-, medium-, and low-dose groups (3, 2, 1.5 g/kg), 18 mice in each group. Another 18 three-month-old C57BL/ 6J mice were chosen as normal control group. All administration groups received relevant medicine for successive 6 months. Then the changes in learning and memory ability of mice were detected by Morris water maze test; pathomorphism in hippocampus CA1 zone was detected by HE staining method; changes of myelin sheath, microtubule, and microfilament in myelinated nerve of hippocampus CA1 zone were detected by electron microscope. Results Morris water maze test results showed that escape incubation period of APP/PS1 transgenic mice was significantly longer than the normal control group (P<0.01), and the original platform time was significantly shorter than normal control group (P<0.01); compared with model control group, Abnormal Phlegmatic Temperament Granules treatment groups escape latency time was significantly reduced (P<0.05, P<0.01). Space experiments and escape incubation period of Abnormal Phlegmatic Temperament Granules high-, medium-, low-dose groups were significantly shortened (P<0.05, P<0.01), and spatial searching test showed that the times of mice in Abnormal Phlegmatic Temperament Granules high-, medium-, low-dose groups passing through effective area increased (P<0.01). The integrity of HE staining pyramidal cell layer in the hippocampus CA1 zones of Abnormal Phlegmatic Temperament Granules high-, medium-, and low-dose groups was relatively good; cells arranged orderly; distribution was normal. Electron microscopic observation showed that compared with model control group, the hippocampus neurons nuclear had irregular shape; nuclear membrane was clear and complete; chromatin was clear; nucleolus was obvious; cell matrix was uniform; organelles were abundant; mitochondrial cristae was obvious; endoplasmic reticulum and free ribosomes were obvious. Conclusion Abnormal Phlegmatic Temperament Granules can improve spatial learning and memory in APP/PS1 mice, alleviate neuronal ultrastructure damage and ultimately improve cognitive function.

The construction of Alzheimer′s disease rats model and the effects of puerarin on rat spatial learning and memory / 重庆医学

Objective To research the effects of puerarin on Alzheimer′s disease(AD) rats spatial learning and memory dis‐order induced by Aβ1‐42 .Methods Bilateral hippocampal injection of Aβ1‐42 was used to induced AD model rats .All rats under‐went gavage administration with puerarin with different dose for 28 d since the 3rd day after the construction of model ;and the Morris water maze was used to test the spatial learning and memory ability of rats .Results The model group rats showed obvious learning and memory disorder ,and the ability of learning and memory disorder of rats in the high ,medium and low dose of puerarin interven‐tion group were significantly improved .Conclusion Puerarin can improve the spatial learning and memory ability of AD model rats .

Long-term Impairment of Spatial Learning and Memory in Rats after Heat Stroke / 中国康复理论与实践

Objective To compare the spatial learning and memory function of heat stroke rats in different periods, to explore the long-term impairment. Methods 42 Sprague-Dawley rats were randomly divided into heat stroke 7 days group (HS7, n=21), heat stroke 21 days group (HS21, n=21), and another 18 rats were performed femoral artery intubation as surgery control group (sham, n=18). They were tested with Morris water maze 7 days and 21 days after modeling respectively for 5 days. The escaping latency, the frequency of crossing the platform area and the duration in the target quadrant were recorded. Results Compared with the sham group, the escaping latency prolonged in HS7 group in all the time (P0.05). Conclusion The impairment of spatial learning and memory is the most seriously 7 days after heat stroke in rats, and it may remain for long time.

Effect of Kidney-tonifying Therapy on Spatial Learning and Memory Abilities of Kidney Deficiency Rats / 广州中医药大学学报

Objective To observe the effects of kidney-tonifying therapy on spatial learning, memory abilities and ultrastructure of hippocampal dentate gyrus ( DG ) cells of kidney deficiency rats induced by sexual intemperance. Methods SD rats with low reproductive capacity were caused by continuously mating for 6 months, and then were randomly divided into 5 groups, namely model group, low- and high-dose of Liuwei Dihuang pills (LDP) groups (in the dosage of 4.8, 9.6 g·kg-1·d-1), low-and high-dose of Jingui Shenqi pills (JSP) group (in the dosage of 5.2, 10.4 g·kg-1·d-1), 8 rats in each group. Except the model group, the other groups were respectively given with the corresponding medication. SD rats aged 2 months served as the normal control group. After treatment for 30 continuous days, the learning and memory abilities of rats were examined by Morris Water Maze. The cell ultra structure of hippocampal dentate gyrus was observed by transmission electron microscopy. Results The results of the place navigation test of Morris water maze showed that the escape latency of rats was prolonged obviously in the model group compared with that of the normal control group (P<0.01), and the escape latency of rats in the medication groups was shorter than the kidney deficiency model group (P<0.05 or P<0.01). The results of spatial probe test showed that the residence time in the former hidden platform quadrant and its surrounding area was significantly shortened in the model group compared with that of the normal control group ( P<0.01) , but was prolonged after medication of high-dose JSP ( P<0.05 or P<0.01 compared with that of the model group). Under the electron microscope, the cell ultra structure lesions of hippocampal dentate gyrus were much relieved in the high-dose LDP group, and high-dose JSP group as compared with those of the model group. Conclusion ( 1) Long-term sexual intemperance can impair spatial learning and memory abilities and causes the cell ultra structure lesions of hippocampal dentate gyrus of rats. (2) The kidney-tonifying therapy can significantly alleviate the spatial learning and memory disturbance and the cell ultra structure lesions of hippocampal dentate gyrus induced by sexual intemperance. ( 3) There are not significant differences between the two kidney-tonifying therapies in improving spatial learning and relieving cell ultra structure lesions. The effect of JSP on improving spatial memory abilities is better than that of LDP.

Effects of memantine on lipopolysaccharide-induced spatial learning and memory impairment in C57BL/6J mice / 医学研究生学报

[Abstract ] Objective The pathogenesis underlying cognitive dysfunction has yet to be fully elucidated.The article was to investigate the effects of memantine on lipopolysaccharide (LPS)-induced spatial learning and memory impairment in C57BL/6J mice. Methods 36 male C57BL/6J mice were randomly divided into 3 groups:control group (C group), lipopolysaccharide group (L group) and memantine group (M group) (n=12).Mice in C, L and M groups were intraperitoneally injected with the same volume of saline, LPS and LPS plus memantine re-spectively for 7 consecutive days.On the 8th day, mice were tested in the Morris water maze, in which the latency to the platform and the propor-tion of time spent in the target quadrant were recorded .Then the mice were sacrificed and the hippocampi were harvested for the determination of expression levels of Amyloid-β(Aβ), glycogen synthase kinase-3β(GSK-3β) and mammalian target of rapamycin (mTOR). Results Com-pared with C group, L group significantly prolongated the latency to the platform (71.01 ±13.21 vs 50.56 ±9.89, P<0.05), decreased the propor-tion of time spent in the target quadrant (42.58 ±7.85 vs 63.74 ±12.43, P<0.05) and increased the levels of hippocampal Aβand GSK-3β(1.75 ±0.43 vs 1.27 ±0.23, 184.0 ±18.6 vs 100.0 ±12.1, P<0.05), (75.0 ±13.5 vs 100.0 ±10.3, P<0.05), while mTOR levels decreased significantly (97.0 ±14.3 vs 75.0 ±13.5, P<0.05).Compared with L group, M group significantly prolongated the latency to the platform (61.45 ±7.65 vs 71.01 ±13.21, P<0.05), decreased the proportion of time spent in the target quadrant shortened (58.25 ±9.02 vs 42.58 ±7.85, P<0.05) and increased the expression of hippocampal Aβ(1.35 ±0.28 vs 1.75 ±0.43,92.4 ±10.8 vs 184.0 ±18.6, P <0.05). Conclusion Memantine contributes to the improvement of LPS-induced spatial learning and memory impairment, which is probably related to the changes of the expression of GSK-3βand mTOR in hippocampus.

Effects of Low Intensity Treadmill Training on Spatial Learning and Memory and Expression of Glycogen Synthase Kinase-3βin Hippocampus in Mice / 中国康复理论与实践

Objective To investigate the effects of low intensity treadmill training on spatial learning and memory and expression of gly-cogen synthase kinase-3β(GSK-3β) in hippocampus in mice. Methods 24 female C57BL/6J mice of 3 months were assigned into control group (n=12) and exercise group (n=12). They were assessed with Morris Water Maze task 5 months after exercise. The GSK-3βprotein and mRNA expressed in hippocampus were determined 1 week after the task. Results The latency and path length to escape onto the hidden plat-form decreased in the exercise group (P<0.05), while the cross times increased (P<0.05) compared with the control group. The level of GSK-3βmRNA decreased (P<0.05) and ratio of p-GSK-3β-Ser9 to GSK-3βincreased (P<0.05) as well. Conclusion Low intensity treadmill exercise may improve the spatial learning and memory in mice, which may down-regulate the expression and activity of GSK-3β.

Effects of recombinant human erythropoietin on learning and memory abilities and expressions of P53 and Bcl-2 proteins in rats induced by chronic cerebral ischemia / 中华神经医学杂志

Objective To study the effects of recombinant human erythropoietin (rhEPO) on learning and memory functions and expressions of apoptosis-related proteins (P53 and Bcl-2) in rats induced by chronic cerebral ischemia.Methods Sixteen healthy male SD rats were randomly divided into control group and experimental group (n=8); the permanent bilateral occlusion of common carotid arteries in these rats was adopted to establish the chronic cerebral ischemia models; rats in the experimental group weekly received intranasal rhEPO delivery at the dose of 150 U/125 μL after chronic ischemia for 3 days,whereas models in the control group accepted equivalent volume of saline at the same time.Eight weeks after the inducement,Morris water maze test was performed to evaluate the movement and the spatial learning and memory capabilities.Morphology changes of cerebral cortex and hippocampal CA1 nerve cells were observed by HE staining.P53 and Bcl-2 proteins levels were detected by immunohistochemistry.The number of apoptotic cells was detected by means of TUNEL.Results Morris water maze test showed that shorter escape latency and higher frequency through platform in the experimental group were noted as compared with those in the control group (P＜0.05).HE staining indicated that less pyramidal cells and more serious karyopyknosis changes of cerebral cortex and hippocampal CA1 nerve cells and thinner cerebral cortex in control group were noted as compared with those in the experimental group (P＜0.05).Immunohistochemistry indicated that the experiment group had increased Bal-2 expression and mean gray value of P53 as compared with control group (P＜0.05).TUNEL showed that the apoptotic cells of control group were significantly increased as compared with those in the experimental group (P＜0.05).Conclusion The rhEPO can improve the abilities of movement,memory and spatial orientation in rats induced by chronic cerebral ischemia,whose mechanism might be related to the restrain apoptosis.