OBJECTIVE Microglia M1/M2 po⁃larization play pro-inflammatory and anti-inflam⁃matory roles,respectively,which is involved in memory decline.There is a close relationship between impaired baroreflex function and memory...OBJECTIVE Microglia M1/M2 po⁃larization play pro-inflammatory and anti-inflam⁃matory roles,respectively,which is involved in memory decline.There is a close relationship between impaired baroreflex function and memory impairment.The present study was designed to investigate whether arterial baroreflex deficiency induced by sinoaortic denervation(SAD)affected inflammation through modulation of M1/M2 polar⁃ization leading to the aggravation of learning and memory disorders in rats.METHODS Adult male SD rats were divided into four groups:the sham control,the SAD,the sham+scopolamine,the SAD+scopolamine.In another experiment,there were also four groups:the sham control,the SAD,the SAD+scopolamine and the SAD+scopolamine+ketanserin.All rats were examined for various behaviors using Morris water maze test,new object recognition test,and light dark shuttle test and Y maze test 4 weeks after sham or SAD surgery.CD16,CD206,IL-10,IL-6,IL-1βand TNF-αfrom hippocampus using Western blotting,immunofluorescence and turbidimetry.RESULTS Compared with the sham+scopol⁃amine,the SAD+scopolamine rats showed the reduced crossing times in Morris water maze test,the longer residence time in dark box during light dark shuttle test,and the decreased alterna⁃tion ratio in Y maze test.The level of CD206,IL-10,T-AOC and GSH was decreased,whereas CD16,IL-6,TNF-α,MDA was increased in the hippocampus of SAD+scopolamine rats.Addi⁃tionally,all the above changes were improved in the SAD+scopolamine+ketanserin rats when compared with the SAD+scopolamine.CONCLU⁃SION Arterial baroreflex dysfunction aggravates learning and memory disorders in rats,which may be related to the polarization of microglia.展开更多
OBJECTIVE To investigate the effects of imperatorin on the spatial learning memory impairment and neuroinflammation in model mice of Alzheimer disease(AD)induced by intracerebroventricular injection of Aβ1-42.METHODS...OBJECTIVE To investigate the effects of imperatorin on the spatial learning memory impairment and neuroinflammation in model mice of Alzheimer disease(AD)induced by intracerebroventricular injection of Aβ1-42.METHODS Mouse model of AD was established by injection of Aβ1-42 into the lateral ventricles.Im⁃peratorin(2.5 and 5.0 mg·kg-1,daily)was inject⁃ed by intraperitoneally 1 h after intracerebroven⁃tricular injection for 13 d.The effect of imperato⁃rin on the spatial learning and memory impair⁃ment was assessed by eight arm maze tests.The levels of cytokines TNF-α,IL-1β,IL-6,IL-18 and chemokines MCP-1 in mouse cortex and hip⁃pocampus were detected by ELISA.The protein expression of NF-κB P65,TLR4,MyD88,p-P38,p-ERK,and p-JNK were detected by Western blotting.RESULTS As compared with the AD model group,imperatorin treatment significantly attenuated Aβ1-42-induced spatial learning and memory impairment assessed by eight arm maze tests.In addition,imperatorin significantly reduced the levels of cytokines TNF-α,IL-1β,IL-6,IL-18 and chemokines MCP-1 in the cerebral cortex and hippocampus.Meanwhile,Western blotting results showed that imperatorin treat⁃ment significantly down-regulated the protein expression of NF-κB P65,TLR4,MyD88,p-P38,p-ERK,and p-JNK.CONCLUSION Imperatorin has neuroprotective effects in the Aβ1-42 induced AD model mice and its mechanism may be partially associated with the inhibition of inflam⁃matory response in the cortex and hippocampus.展开更多
OBJECTIVE To observe the effects of betaine on learning memory in SHR rats through behavioral experiments,and then to investigate the mechanisms of betaine to improve the cognitive impairment caused by hyperten⁃sion.M...OBJECTIVE To observe the effects of betaine on learning memory in SHR rats through behavioral experiments,and then to investigate the mechanisms of betaine to improve the cognitive impairment caused by hyperten⁃sion.METHODS 4-month-old male SHR rats were randomly divided into 4 groups,including betaine 10,30 and 100 mg·kg-1 groups and SHR group,and administered by gavage,10 mL·kg-1 once a day for 4 weeks.The control group was WKY rats,and the same amount of saline was given by gavage.The learning and memory behaviors of the rats were analyzed and evaluated through behavioral testing.RESULTS The results of Morris water maze showed that persistent hypertension decreased the time in the target quadrant and the number of platform crossing of the rats,and the intervention with different con⁃centrations of betaine increased the time in the target quadrant and the number of platform crossing of SHR in a dose-dependent manner.Then,persistent hypertension increased the escape latency of rats,and betaine inhibited this change.The results of new object recognition showed that the recognition index of SHR group decreased,and the recognition index of SHR rats increased with different concentrations of betaine intervention in a dose-dependent manner.The Y-maze results showed that persistent hypertension decreased the alternation in rats,and the alternation in SHR rats increased after the intervention with different concentrations of betaine,and in a dose-dependent manner.CON⁃CLUSION Persistent hypertension can cause learning memory impairment in rats.Betaine intervention has an ameliorative effect on the reduction of learning memory ability in rats caused by hypertension.展开更多
This study aimed to elucidate whether midazolam affected the learning and memory of rats through the extracellular signal-regulated kinase(ERK)/cyclic adenosine monophosphate response element-binding(CREB)signaling pa...This study aimed to elucidate whether midazolam affected the learning and memory of rats through the extracellular signal-regulated kinase(ERK)/cyclic adenosine monophosphate response element-binding(CREB)signaling pathway and hippocampal oxidative damage.Overall 120 Wistar rats were randomly assigned to four groups,including one control and three midazolam-exposed groups(20,60 and 150 mg•kg^(-1)).After an intraperitoneal injection of midazolam/physiological saline for both 1 h(n=15)and 24 h(n=15),10 rats(five came from 1 h,and the remaining five came from 24 h)were randomly selected from each group for the Morris water maze test.The hippocampus tissue samples were harvested for the assessment of superoxide dismutase(SOD)and catalase(CAT)activities as well as glutathione peroxidase(GPx),malonyl dialdehyde(MDA),nitric oxide(NO)and inducible nitric oxide synthase(iNOS)levels.The remaining 80 rats were euthanized,and the hippocampal tissue was isolated.The expressions of ERK1,ERK2 and CREB mRNA were tested using RT-qPCR.The protein expressions of p-ERK1/2 and p-CREB were tested using Western blotting.The Morris water maze tests indicated that midazolam-treated rats have weaker learning and memory ability compared to the control rats.Midazolam increased MDA,NO,iNOS and CAT,and decreased GPx and SOD activities compared to the control group.The expression levels of ERK1/2 and CREB in the hippocampus of rats in the midazolam treatment groups were significantly lower compared to the control group at 1 h after intraperitoneal injection of midazolam,and in a dose-dependent relationship but returning it to normal levels at 24 h after midazolam intraperitoneal injection.Therefore,it was concluded that the learning and memory impairment of midazolam might be associated with the down-regulation of the ERK/CREB signaling pathway and oxidative damage in rat hippocampus.展开更多
OBJECTIVE To investigate the influence of gingerol on the improvement of learning and memory impairment of rat model of Alzheimer disease induced by β-amyloid peptide fragment 25-35(Aβ_(25-35)) and to analysis the p...OBJECTIVE To investigate the influence of gingerol on the improvement of learning and memory impairment of rat model of Alzheimer disease induced by β-amyloid peptide fragment 25-35(Aβ_(25-35)) and to analysis the possible mechanism. METHODS SD rats were randomly divided into 5groups: blank control group,model group,sham-operated group,low dose drug group(gingerol emulsion,10 mg·kg^(-1)·d^(-1)),high dose drug group(gingerol emulsion,50 mg·kg^(-1)·d^(-1)). Model group and two drug groups were injected Aβ_(25-35)(5 μL) in lateral cerebral ventricle. Sham-operated group were injected the same amount of sterile PBS solution. For blank control group without any treatment. When all the rats refresh themselves and had post-operated activities,two drug groups were gavaged with different concentration of gingerol emulsion,Meanwhile,sham-operated group were gavaged with sterile physiological saline,the remaining two groups without any treatment. After three weeks,we make use of Y labyrinth to test the ability of space learning and memory of rats. Finally,rats were sacrificed to collect blood by abdominal aortic method. The content of acetylcholine(ACh),SOD and MDA were detected in serum. RESULTS(1) Compared with blank control group,the ability of learning and memory of model group rats were weakened,the error times increased in Y labyrinth experiment. In addition,the content of ACh and the activity of SOD significantly decreased,the content of MDA increased(P<0.05).(2) On the contrary,the rats gavaged with gingerol emusion have less error times in Y labyrinth experiment compared with model group. the content of Ach and the activity of SOD significantly increased,the content of MDA decreased(P<0.05). However,two different gingerol emusion concentration groups have no significantly difference. CONCLUSION The ability of learning and memory of rats gavaged with gingerol emusion were significantly improved compared with Aβ_(25-35) induced rats without any treatment.Its mechanism may be related to antioxidant and neurotransmitter.展开更多
OBJECTIVE Learning and memory impairment is one of the common sequelae of stroke patients,which is called"post-stroke dementia"and seriously affects the quality of life of the patients.For post-stroke dement...OBJECTIVE Learning and memory impairment is one of the common sequelae of stroke patients,which is called"post-stroke dementia"and seriously affects the quality of life of the patients.For post-stroke dementia,there is still no effective clinical treatment.In the present study,we aim to investigate the effect of the active ingredient of Ferula sinkiangensis,AW09,on global cerebral ischemia-reperfusion mice.METHODS The bilateral common carotid artery occlusion(BCCAO)reperfusion model was used to investigate the protective effect of AW09 on cognitive dysfunction in mice with global cerebral ischemia reperfusion.Y-maze and Morris water maze were used to test the learning and memory ability of mice.RESULTS Y-maze test showed that AW09 treatment significantly increased the spontaneous alternation rate of BCCAO model animals and had no significant effect on the total number of arm entries.The results of Morris water maze showed that AW09 significantly reduced the escape latency of BCCAO mice during the training period.During the probe test phase,AW09 significantly increased the swimming time in target quadrant,distance in target quadrant and number of platform crossings and decreased the swimming time in the quadrant opposite the target quadrant of BCCAO mice.CONCLUSION AW09,the active ingredient of Ferula sinkiangensis,can improve working memory impairment and spatial memory impairment in animals with global cerebral ischemia-reperfusion,suggesting that AW09 has poten⁃tial therapeutic value for cognitive dysfunction caused by global cerebral ischemia.展开更多
基金Natural Science Foundation of Shandong Province(ZR2017MH048)。
文摘OBJECTIVE Microglia M1/M2 po⁃larization play pro-inflammatory and anti-inflam⁃matory roles,respectively,which is involved in memory decline.There is a close relationship between impaired baroreflex function and memory impairment.The present study was designed to investigate whether arterial baroreflex deficiency induced by sinoaortic denervation(SAD)affected inflammation through modulation of M1/M2 polar⁃ization leading to the aggravation of learning and memory disorders in rats.METHODS Adult male SD rats were divided into four groups:the sham control,the SAD,the sham+scopolamine,the SAD+scopolamine.In another experiment,there were also four groups:the sham control,the SAD,the SAD+scopolamine and the SAD+scopolamine+ketanserin.All rats were examined for various behaviors using Morris water maze test,new object recognition test,and light dark shuttle test and Y maze test 4 weeks after sham or SAD surgery.CD16,CD206,IL-10,IL-6,IL-1βand TNF-αfrom hippocampus using Western blotting,immunofluorescence and turbidimetry.RESULTS Compared with the sham+scopol⁃amine,the SAD+scopolamine rats showed the reduced crossing times in Morris water maze test,the longer residence time in dark box during light dark shuttle test,and the decreased alterna⁃tion ratio in Y maze test.The level of CD206,IL-10,T-AOC and GSH was decreased,whereas CD16,IL-6,TNF-α,MDA was increased in the hippocampus of SAD+scopolamine rats.Addi⁃tionally,all the above changes were improved in the SAD+scopolamine+ketanserin rats when compared with the SAD+scopolamine.CONCLU⁃SION Arterial baroreflex dysfunction aggravates learning and memory disorders in rats,which may be related to the polarization of microglia.
文摘OBJECTIVE To investigate the effects of imperatorin on the spatial learning memory impairment and neuroinflammation in model mice of Alzheimer disease(AD)induced by intracerebroventricular injection of Aβ1-42.METHODS Mouse model of AD was established by injection of Aβ1-42 into the lateral ventricles.Im⁃peratorin(2.5 and 5.0 mg·kg-1,daily)was inject⁃ed by intraperitoneally 1 h after intracerebroven⁃tricular injection for 13 d.The effect of imperato⁃rin on the spatial learning and memory impair⁃ment was assessed by eight arm maze tests.The levels of cytokines TNF-α,IL-1β,IL-6,IL-18 and chemokines MCP-1 in mouse cortex and hip⁃pocampus were detected by ELISA.The protein expression of NF-κB P65,TLR4,MyD88,p-P38,p-ERK,and p-JNK were detected by Western blotting.RESULTS As compared with the AD model group,imperatorin treatment significantly attenuated Aβ1-42-induced spatial learning and memory impairment assessed by eight arm maze tests.In addition,imperatorin significantly reduced the levels of cytokines TNF-α,IL-1β,IL-6,IL-18 and chemokines MCP-1 in the cerebral cortex and hippocampus.Meanwhile,Western blotting results showed that imperatorin treat⁃ment significantly down-regulated the protein expression of NF-κB P65,TLR4,MyD88,p-P38,p-ERK,and p-JNK.CONCLUSION Imperatorin has neuroprotective effects in the Aβ1-42 induced AD model mice and its mechanism may be partially associated with the inhibition of inflam⁃matory response in the cortex and hippocampus.
基金National Natural Science Foundation of China(81400182)and Natural Science Foundation of Shandong Province(BS2014YY045)。
文摘OBJECTIVE To observe the effects of betaine on learning memory in SHR rats through behavioral experiments,and then to investigate the mechanisms of betaine to improve the cognitive impairment caused by hyperten⁃sion.METHODS 4-month-old male SHR rats were randomly divided into 4 groups,including betaine 10,30 and 100 mg·kg-1 groups and SHR group,and administered by gavage,10 mL·kg-1 once a day for 4 weeks.The control group was WKY rats,and the same amount of saline was given by gavage.The learning and memory behaviors of the rats were analyzed and evaluated through behavioral testing.RESULTS The results of Morris water maze showed that persistent hypertension decreased the time in the target quadrant and the number of platform crossing of the rats,and the intervention with different con⁃centrations of betaine increased the time in the target quadrant and the number of platform crossing of SHR in a dose-dependent manner.Then,persistent hypertension increased the escape latency of rats,and betaine inhibited this change.The results of new object recognition showed that the recognition index of SHR group decreased,and the recognition index of SHR rats increased with different concentrations of betaine intervention in a dose-dependent manner.The Y-maze results showed that persistent hypertension decreased the alternation in rats,and the alternation in SHR rats increased after the intervention with different concentrations of betaine,and in a dose-dependent manner.CON⁃CLUSION Persistent hypertension can cause learning memory impairment in rats.Betaine intervention has an ameliorative effect on the reduction of learning memory ability in rats caused by hypertension.
基金Supported by the National Natural Science Foundation of China(32273078)the Applied Technology Research and Development Plan of Heilongjiang Province(GX18B023)。
文摘This study aimed to elucidate whether midazolam affected the learning and memory of rats through the extracellular signal-regulated kinase(ERK)/cyclic adenosine monophosphate response element-binding(CREB)signaling pathway and hippocampal oxidative damage.Overall 120 Wistar rats were randomly assigned to four groups,including one control and three midazolam-exposed groups(20,60 and 150 mg•kg^(-1)).After an intraperitoneal injection of midazolam/physiological saline for both 1 h(n=15)and 24 h(n=15),10 rats(five came from 1 h,and the remaining five came from 24 h)were randomly selected from each group for the Morris water maze test.The hippocampus tissue samples were harvested for the assessment of superoxide dismutase(SOD)and catalase(CAT)activities as well as glutathione peroxidase(GPx),malonyl dialdehyde(MDA),nitric oxide(NO)and inducible nitric oxide synthase(iNOS)levels.The remaining 80 rats were euthanized,and the hippocampal tissue was isolated.The expressions of ERK1,ERK2 and CREB mRNA were tested using RT-qPCR.The protein expressions of p-ERK1/2 and p-CREB were tested using Western blotting.The Morris water maze tests indicated that midazolam-treated rats have weaker learning and memory ability compared to the control rats.Midazolam increased MDA,NO,iNOS and CAT,and decreased GPx and SOD activities compared to the control group.The expression levels of ERK1/2 and CREB in the hippocampus of rats in the midazolam treatment groups were significantly lower compared to the control group at 1 h after intraperitoneal injection of midazolam,and in a dose-dependent relationship but returning it to normal levels at 24 h after midazolam intraperitoneal injection.Therefore,it was concluded that the learning and memory impairment of midazolam might be associated with the down-regulation of the ERK/CREB signaling pathway and oxidative damage in rat hippocampus.
基金The project supported by National College Students'Innovative and Entrepreneurial Training Project(201510439078)Science and Technology Development Plan of Tai'an City(201540707)
文摘OBJECTIVE To investigate the influence of gingerol on the improvement of learning and memory impairment of rat model of Alzheimer disease induced by β-amyloid peptide fragment 25-35(Aβ_(25-35)) and to analysis the possible mechanism. METHODS SD rats were randomly divided into 5groups: blank control group,model group,sham-operated group,low dose drug group(gingerol emulsion,10 mg·kg^(-1)·d^(-1)),high dose drug group(gingerol emulsion,50 mg·kg^(-1)·d^(-1)). Model group and two drug groups were injected Aβ_(25-35)(5 μL) in lateral cerebral ventricle. Sham-operated group were injected the same amount of sterile PBS solution. For blank control group without any treatment. When all the rats refresh themselves and had post-operated activities,two drug groups were gavaged with different concentration of gingerol emulsion,Meanwhile,sham-operated group were gavaged with sterile physiological saline,the remaining two groups without any treatment. After three weeks,we make use of Y labyrinth to test the ability of space learning and memory of rats. Finally,rats were sacrificed to collect blood by abdominal aortic method. The content of acetylcholine(ACh),SOD and MDA were detected in serum. RESULTS(1) Compared with blank control group,the ability of learning and memory of model group rats were weakened,the error times increased in Y labyrinth experiment. In addition,the content of ACh and the activity of SOD significantly decreased,the content of MDA increased(P<0.05).(2) On the contrary,the rats gavaged with gingerol emusion have less error times in Y labyrinth experiment compared with model group. the content of Ach and the activity of SOD significantly increased,the content of MDA decreased(P<0.05). However,two different gingerol emusion concentration groups have no significantly difference. CONCLUSION The ability of learning and memory of rats gavaged with gingerol emusion were significantly improved compared with Aβ_(25-35) induced rats without any treatment.Its mechanism may be related to antioxidant and neurotransmitter.
基金National Natural Science Foundation of China(U160312581473330+5 种基金8187276881673323)Fundamental Research Funds for the Central Universities of China(N182008004N182006001)Liaoning Revitalization Talents Program(XLYC1807118)Liaoning BaiQianWan Talents Program(2018)
文摘OBJECTIVE Learning and memory impairment is one of the common sequelae of stroke patients,which is called"post-stroke dementia"and seriously affects the quality of life of the patients.For post-stroke dementia,there is still no effective clinical treatment.In the present study,we aim to investigate the effect of the active ingredient of Ferula sinkiangensis,AW09,on global cerebral ischemia-reperfusion mice.METHODS The bilateral common carotid artery occlusion(BCCAO)reperfusion model was used to investigate the protective effect of AW09 on cognitive dysfunction in mice with global cerebral ischemia reperfusion.Y-maze and Morris water maze were used to test the learning and memory ability of mice.RESULTS Y-maze test showed that AW09 treatment significantly increased the spontaneous alternation rate of BCCAO model animals and had no significant effect on the total number of arm entries.The results of Morris water maze showed that AW09 significantly reduced the escape latency of BCCAO mice during the training period.During the probe test phase,AW09 significantly increased the swimming time in target quadrant,distance in target quadrant and number of platform crossings and decreased the swimming time in the quadrant opposite the target quadrant of BCCAO mice.CONCLUSION AW09,the active ingredient of Ferula sinkiangensis,can improve working memory impairment and spatial memory impairment in animals with global cerebral ischemia-reperfusion,suggesting that AW09 has poten⁃tial therapeutic value for cognitive dysfunction caused by global cerebral ischemia.
