Background:The chronic unpredictable mild stress(CUMS)model has long been considered the best model for exploring the pathophysiological mechanisms underlying depression.However,there are no widely recognised standard...Background:The chronic unpredictable mild stress(CUMS)model has long been considered the best model for exploring the pathophysiological mechanisms underlying depression.However,there are no widely recognised standards for strategies for modeling and for behavioral testing.The present study aimed to optimize the protocols for food deprivation and the sucrose preference test(SPT)for the CUMS model.Methods:We first evaluated the effects of different long periods of food deprivation on the body weight of Sprague Dawley(SD)rats by testing food deprivation for 24 hours(8:00-8:00^+),food deprivation for 12 hours during the daytime(8:00-20:00)and food deprivation for 12 hours at night(20:00-8:00^+).Next,we established a SD rat CUMS model with 15 different stimulations,and used body weight measurement,SPT,forced swim test(FST),open field test(OFT)and Morris water maze(MWM)test to verify the success of the modeling.In the SPT,consumption of sucrose and pure water within 1 and 12 hours was measured.Results:Twelve hours of food deprivation during the daytime(8:00-20:00)had no effect on body weight,while 12 hours of food deprivation at night(20:00-8:00^+)and 24 hours of food deprivation(8:00-8:00^+)significantly reduced the mean body weight of the SD rats.When SPT was used to verify the successful establishment of the CUMS rat model,sucrose consumption measured within 12 hours was less variable than that measured within 1 hour.Conclusions:Twelve hours of food deprivation in the daytime(8:00-20:00)may be considered a mild stimulus for the establishment of a CUMS rat model.Measuring sucrose consumption over 12 hours is recommended for SPT.展开更多
Objective Previous research indicates a link between cognitive impairment and chronic kidney disease(CKD),but the underlying factors are not fully understood.This study aimed to investigate the progression of CKD-indu...Objective Previous research indicates a link between cognitive impairment and chronic kidney disease(CKD),but the underlying factors are not fully understood.This study aimed to investigate the progression of CKD-induced cognitive impairment and the involvement of cognition-related proteins by developing early-and late-stage CKD models in Sprague-Dawley rats.Methods The Morris water maze test and the step-down passive avoidance task were performed to evaluate the cognitive abilities of the rats at 24 weeks after surgery.Histopathologic examinations were conducted to examine renal and hippocampal damage.Real-time PCR,Western blotting analysis,and immunohistochemical staining were carried out to determine the hippocampal expression of brain-derived neurotrophic factor(BDNF),choline acetyltransferase(ChAT),and synaptophysin(SYP).Results Compared with the control rats,the rats with early-stage CKD exhibited mild renal damage,while those with late-stage CKD showed significantly increased serum creatinine levels as well as apparent renal and brain damage.The rats with early-stage CKD also demonstrated significantly impaired learning abilities and memory compared with the control rats,with further deterioration observed in the rats with late-stage CKD.Additionally,we observed a significant downregulation of cognition-related proteins in the hippocampus of rats with early-stage CKD,which was further exacerbated with declining renal function as well as worsening brain and renal damage in rats with late-stage CKD.Conclusion These results suggest the importance of early screening to identify CKD-induced cognitive dysfunction promptly.In addition,the downregulation of cognition-related proteins may play a role in the progression of cognitive dysfunction.展开更多
Ischemic brain injury causes neuronal death and inflammation.Inflammation activates protein-tyrosine phosphatase 1B(PTP1B).Here,we tested the significance of PTP1B activation in glutamatergic projection neurons on fun...Ischemic brain injury causes neuronal death and inflammation.Inflammation activates protein-tyrosine phosphatase 1B(PTP1B).Here,we tested the significance of PTP1B activation in glutamatergic projection neurons on functional recovery in two models of stroke:by photothrombosis,focal ischemic lesions were induced in the sensorimotor cortex(SM stroke)or in the peri-prefrontal cortex(peri-PFC stroke).Elevated PTP1B expression was detected at 4 days and up to 6 weeks after stroke.While ablation of PTP1B in neurons of neuronal knockout(NKO)mice had no effect on the volume or resorption of ischemic lesions,markedly different effects on functional recovery were observed.SM stroke caused severe sensory and motor deficits(adhesive removal test)in wild type and NKO mice at 4 days,but NKO mice showed drastically improved sensory and motor functional recovery at 8 days.In addition,peri-PFC stroke caused anxiety-like behaviors(elevated plus maze and open field tests),and depression-like behaviors(forced swimming and tail suspension tests)in wild type mice 9 and 28 days after stroke,respectively,with minimal effect on sensory and motor function.Peri-PFC stroke-induced affective disorders were associated with fewer active(FosB+)neurons in the PFC and nucleus accumbens but more FosB+neurons in the basolateral amygdala,compared to sham-operated mice.In contrast,mice with neuronal ablation of PTP1B were protected from anxiety-like and depression-like behaviors and showed no change in FosB+neurons after peri-PFC stroke.Taken together,our study identifies neuronal PTP1B as a key component that hinders sensory and motor functional recovery and also contributes to the development of anxiety-like and depression-like behaviors after stroke.Thus,PTP1B may represent a novel therapeutic target to improve stroke recovery.All procedures for animal use were approved by the Animal Care and Use Committee of the University of Ottawa Animal Care and Veterinary Service(protocol 1806)on July 27,2018.展开更多
A generally forgotten means of observing the developmental stages of scientific psychology is the study of maze devices. Considered in ancient times as a symbol of the process of moving in the direction of knowledge, ...A generally forgotten means of observing the developmental stages of scientific psychology is the study of maze devices. Considered in ancient times as a symbol of the process of moving in the direction of knowledge, the labyrinth, or maze, was at the centre of psychologists’ attention from the end of the 19th century. The current paper aims to reconstruct the history of the early years of maze learning, starting from the original interests of the experimenters in brain physiology or in mental evolution, and to examine how the experiments they designed continued to be important in the general theory of learning throughout the 20th century: maze studies helped uncover general principles about learning that can be applied to many species, including humans. At the beginning of the 21st century the question has become: what parts of the brain are used for spatial learning and memory, as shown by the Morris water maze, which is very popular in studies of behavioural neuroscience.展开更多
OBJECTIVE:Angelica archangelica Linn.is widely used in food and liquor preparations and also in Kashmiri folk medicine to reduce anxiety.We evaluated the anxiolytic effect of successive extracts of A.archangelica linn...OBJECTIVE:Angelica archangelica Linn.is widely used in food and liquor preparations and also in Kashmiri folk medicine to reduce anxiety.We evaluated the anxiolytic effect of successive extracts of A.archangelica linn.(SAE) on rats tested in the elevated T-maze test(an animal model of generalized anxiety) at doses that exhibit antidepressant-like activity in humans.METHODS:A.archangelica(1 kg) was subjected to successive extraction in a soxhlet apparatus with solvents [petroleum ether(40-60℃),chloroform,ethyl acetate,methanol and decoction with water] in order of increasing polarity(yield:6.9%,7.3%,5.1%,11.88% and 8.2% w/w,respectively).SAE were evaluated for anxiolytic effects using the elevated T-maze and forced swimming tests in rats.RESULTS:Oral dosing of diazepam(1 mg/kg) and extracts(50,100 and 200 mg/kg) clearly showed an anxiolytic-like profile in the elevated T-maze test:it increased one-way escape and decreased inhibitory avoidance on the first,third and seventh day.In the forced swimming test,imipramine and SAE showed antidepressant-and anxiolytic-like effects as reflected by increased climbing time,swimming time and decreased immobility time on the first,third and seventh day.Aqueous and methanol extracts showed the most,petroleum ether(40-60℃) and chloroform intermediate,and ethyl acetate the least anxiolytic activity(*P<0.05,**P<0.01,***P< 0.001) in both models.CONCLUSIONS:These results suggest the anti-anxiety activity of various extracts of A.archangelica and strongly justify its use in traditional Indian medicine for the treatment of anxiety.展开更多
Longterm potentiation (LTP ) is usually induced by direct brain stimulation. An attempt has been made to evoke LTP in dentate granule cells of hippocampus by acupoint stimulation in anesthetized rats. Assuming a gradu...Longterm potentiation (LTP ) is usually induced by direct brain stimulation. An attempt has been made to evoke LTP in dentate granule cells of hippocampus by acupoint stimulation in anesthetized rats. Assuming a gradual increasing course, LTP rose to 146% at the end of one hour. After applying such stimulation to the awake rats for six days (once everyday), their discriminative learning capacity in Y maze test markedly improved as compared with that of the control.展开更多
基金This work was supported by Social livelihood projects of Chongqing Science and Technology Bureau(cstc2017shms-zdyfX0048,csts2017shmsA00007).
文摘Background:The chronic unpredictable mild stress(CUMS)model has long been considered the best model for exploring the pathophysiological mechanisms underlying depression.However,there are no widely recognised standards for strategies for modeling and for behavioral testing.The present study aimed to optimize the protocols for food deprivation and the sucrose preference test(SPT)for the CUMS model.Methods:We first evaluated the effects of different long periods of food deprivation on the body weight of Sprague Dawley(SD)rats by testing food deprivation for 24 hours(8:00-8:00^+),food deprivation for 12 hours during the daytime(8:00-20:00)and food deprivation for 12 hours at night(20:00-8:00^+).Next,we established a SD rat CUMS model with 15 different stimulations,and used body weight measurement,SPT,forced swim test(FST),open field test(OFT)and Morris water maze(MWM)test to verify the success of the modeling.In the SPT,consumption of sucrose and pure water within 1 and 12 hours was measured.Results:Twelve hours of food deprivation during the daytime(8:00-20:00)had no effect on body weight,while 12 hours of food deprivation at night(20:00-8:00^+)and 24 hours of food deprivation(8:00-8:00^+)significantly reduced the mean body weight of the SD rats.When SPT was used to verify the successful establishment of the CUMS rat model,sucrose consumption measured within 12 hours was less variable than that measured within 1 hour.Conclusions:Twelve hours of food deprivation in the daytime(8:00-20:00)may be considered a mild stimulus for the establishment of a CUMS rat model.Measuring sucrose consumption over 12 hours is recommended for SPT.
基金the Youth Fund of the Shanghai Municipal Health Commission(No.20164Y0266).
文摘Objective Previous research indicates a link between cognitive impairment and chronic kidney disease(CKD),but the underlying factors are not fully understood.This study aimed to investigate the progression of CKD-induced cognitive impairment and the involvement of cognition-related proteins by developing early-and late-stage CKD models in Sprague-Dawley rats.Methods The Morris water maze test and the step-down passive avoidance task were performed to evaluate the cognitive abilities of the rats at 24 weeks after surgery.Histopathologic examinations were conducted to examine renal and hippocampal damage.Real-time PCR,Western blotting analysis,and immunohistochemical staining were carried out to determine the hippocampal expression of brain-derived neurotrophic factor(BDNF),choline acetyltransferase(ChAT),and synaptophysin(SYP).Results Compared with the control rats,the rats with early-stage CKD exhibited mild renal damage,while those with late-stage CKD showed significantly increased serum creatinine levels as well as apparent renal and brain damage.The rats with early-stage CKD also demonstrated significantly impaired learning abilities and memory compared with the control rats,with further deterioration observed in the rats with late-stage CKD.Additionally,we observed a significant downregulation of cognition-related proteins in the hippocampus of rats with early-stage CKD,which was further exacerbated with declining renal function as well as worsening brain and renal damage in rats with late-stage CKD.Conclusion These results suggest the importance of early screening to identify CKD-induced cognitive dysfunction promptly.In addition,the downregulation of cognition-related proteins may play a role in the progression of cognitive dysfunction.
基金This work was supported by grants from the Heart and Stroke Foundation of Canada(Nos.G-13-0002596&G-18-0022157,to HHCNo.G-16-00014085,to AFRS)+2 种基金the Natural Science and Engineering Research Council of Canada(No.RGPIN/06212-2014,to HHC,No.RGPIN/2016-04985,to AFRS)the Canadian Institutes of Health Research(No.201610PJT,to HHC)HHC is also supported by a Mid-Career Investigator Award(No.7506)from the Heart and Stroke Foundation of Ontario.How to cite this article:Cruz SA。
文摘Ischemic brain injury causes neuronal death and inflammation.Inflammation activates protein-tyrosine phosphatase 1B(PTP1B).Here,we tested the significance of PTP1B activation in glutamatergic projection neurons on functional recovery in two models of stroke:by photothrombosis,focal ischemic lesions were induced in the sensorimotor cortex(SM stroke)or in the peri-prefrontal cortex(peri-PFC stroke).Elevated PTP1B expression was detected at 4 days and up to 6 weeks after stroke.While ablation of PTP1B in neurons of neuronal knockout(NKO)mice had no effect on the volume or resorption of ischemic lesions,markedly different effects on functional recovery were observed.SM stroke caused severe sensory and motor deficits(adhesive removal test)in wild type and NKO mice at 4 days,but NKO mice showed drastically improved sensory and motor functional recovery at 8 days.In addition,peri-PFC stroke caused anxiety-like behaviors(elevated plus maze and open field tests),and depression-like behaviors(forced swimming and tail suspension tests)in wild type mice 9 and 28 days after stroke,respectively,with minimal effect on sensory and motor function.Peri-PFC stroke-induced affective disorders were associated with fewer active(FosB+)neurons in the PFC and nucleus accumbens but more FosB+neurons in the basolateral amygdala,compared to sham-operated mice.In contrast,mice with neuronal ablation of PTP1B were protected from anxiety-like and depression-like behaviors and showed no change in FosB+neurons after peri-PFC stroke.Taken together,our study identifies neuronal PTP1B as a key component that hinders sensory and motor functional recovery and also contributes to the development of anxiety-like and depression-like behaviors after stroke.Thus,PTP1B may represent a novel therapeutic target to improve stroke recovery.All procedures for animal use were approved by the Animal Care and Use Committee of the University of Ottawa Animal Care and Veterinary Service(protocol 1806)on July 27,2018.
文摘A generally forgotten means of observing the developmental stages of scientific psychology is the study of maze devices. Considered in ancient times as a symbol of the process of moving in the direction of knowledge, the labyrinth, or maze, was at the centre of psychologists’ attention from the end of the 19th century. The current paper aims to reconstruct the history of the early years of maze learning, starting from the original interests of the experimenters in brain physiology or in mental evolution, and to examine how the experiments they designed continued to be important in the general theory of learning throughout the 20th century: maze studies helped uncover general principles about learning that can be applied to many species, including humans. At the beginning of the 21st century the question has become: what parts of the brain are used for spatial learning and memory, as shown by the Morris water maze, which is very popular in studies of behavioural neuroscience.
文摘OBJECTIVE:Angelica archangelica Linn.is widely used in food and liquor preparations and also in Kashmiri folk medicine to reduce anxiety.We evaluated the anxiolytic effect of successive extracts of A.archangelica linn.(SAE) on rats tested in the elevated T-maze test(an animal model of generalized anxiety) at doses that exhibit antidepressant-like activity in humans.METHODS:A.archangelica(1 kg) was subjected to successive extraction in a soxhlet apparatus with solvents [petroleum ether(40-60℃),chloroform,ethyl acetate,methanol and decoction with water] in order of increasing polarity(yield:6.9%,7.3%,5.1%,11.88% and 8.2% w/w,respectively).SAE were evaluated for anxiolytic effects using the elevated T-maze and forced swimming tests in rats.RESULTS:Oral dosing of diazepam(1 mg/kg) and extracts(50,100 and 200 mg/kg) clearly showed an anxiolytic-like profile in the elevated T-maze test:it increased one-way escape and decreased inhibitory avoidance on the first,third and seventh day.In the forced swimming test,imipramine and SAE showed antidepressant-and anxiolytic-like effects as reflected by increased climbing time,swimming time and decreased immobility time on the first,third and seventh day.Aqueous and methanol extracts showed the most,petroleum ether(40-60℃) and chloroform intermediate,and ethyl acetate the least anxiolytic activity(*P<0.05,**P<0.01,***P< 0.001) in both models.CONCLUSIONS:These results suggest the anti-anxiety activity of various extracts of A.archangelica and strongly justify its use in traditional Indian medicine for the treatment of anxiety.
文摘Longterm potentiation (LTP ) is usually induced by direct brain stimulation. An attempt has been made to evoke LTP in dentate granule cells of hippocampus by acupoint stimulation in anesthetized rats. Assuming a gradual increasing course, LTP rose to 146% at the end of one hour. After applying such stimulation to the awake rats for six days (once everyday), their discriminative learning capacity in Y maze test markedly improved as compared with that of the control.
