Background:Vascular cognitive impairment caused by chronic cerebral hypoperfusion(CCH)has become a hot issue worldwide.Aerobic exercise positively contributes to the preservation or restoration of cognitive abilities;...Background:Vascular cognitive impairment caused by chronic cerebral hypoperfusion(CCH)has become a hot issue worldwide.Aerobic exercise positively contributes to the preservation or restoration of cognitive abilities;however,the specific mechanism has remained inconclusive.And recent studies found that neurogranin(Ng)is a potential biomarker for cognitive impairment.This study aims to investigate the underlying role of Ng in swimming training to improve cognitive impairment.Methods:To test this hypothesis,the clustered regularly interspaced short palindromic repeats(CRISPR)-associated protein 9(Cas9)system was utilized to construct a strain of Ng conditional knockout(Ng cKO)mice,and bilateral common carotid artery stenosis(BCAS)surgery was performed to prepare the model.In Experiment 1,2-month-old male and female transgenic mice were divided into a control group(wild-type littermate,n=9)and a Ng cKO group(n=9).Then,2-month-old male and female C57BL/6 mice were divided into a sham group(C57BL/6,n=12)and a BCAS group(n=12).In Experiment 2,2-month-old male and female mice were divided into a sham group(wild-type littermate,n=12),BCAS group(n=12),swim group(n=12),BCAS+Ng cKO group(n=12),and swim+Ng cKO group(n=12).Then,7 days after BCAS,mice were given swimming training for 5 weeks(1 week for adaptation and 4 weeks for training,5 days a week,60 min a day).After intervention,laser speckle was used to detect cerebral blood perfusion in the mice,and the T maze and Morris water maze were adopted to test their spatial memory.Furthermore,electrophysiology and Western blotting were conducted to record long-term potential and observe the expressions of Ca^(2+)pathway-related proteins,respectively.Immunohistochemistry was applied to analyze the expression of relevant markers in neuronal damage,inflammation,and white matter injury.Results:The figures showed that spatial memory impairment was detected in Ng cKO mice,and a sharp decline of cerebral blood flow and an impairment of progressive spatial memory were observed in BCAS mice.Regular swimming training improved the spatial memory impairment of BCAS mice.This was achieved by preventing long-term potential damage and reversing the decline of Ca^(2+)signal transduction pathway-related proteins.At the same time,the results suggested that swimming also led to improvements in neuronal death,inflammation,and white matter injury induced by CCH.Further study adopted the use of Ng cKO transgenic mice,and the results indicated that the positive effects of swimming training on cognitive impairments,synaptic plasticity,and related pathological changes caused by CCH could be abolished by the knockout of Ng.Conclusion:Swimming training can mediate the expression of Ng to enhance hippocampal synaptic plasticity and improve related pathological changes induced by CCH,thereby ameliorating the spatial memory impairment of vascular cognitive impairment.展开更多
Here we tested the hypothesis that stress-induced alterations in Neurogranin (Ng) synthesis and/ or utilization might underlie stress-related depression and anxiety. Rats were randomly divided into five conditions: ch...Here we tested the hypothesis that stress-induced alterations in Neurogranin (Ng) synthesis and/ or utilization might underlie stress-related depression and anxiety. Rats were randomly divided into five conditions: chronic swim stress (CS), acute swim stress (AS), and three control groups. The CS group was exposed to daily swim stress (5 min/day) for 14 consecutive days, the AS group received a single swim stress, and control groups were maintained in a stress-free condition. Both before and after swim stress, rats were tested for body weight gain, open-field locomotor activity, and saccharine preference. Ng and phospho-Ng (P-Ng) levels in the hippocampus and prefrontal cortex were determined by Western blot analysis. Compared to controls, CS animals displayed significantly decreased body weight gain, ambulation, and saccharine intake, and increased grooming behavior. CS animals had decreased Ng levels in the hippocampus and prefrontal cortex. In CS animals, Ng levels were positively correlated with saccharine intake and ambulation, and inversely correlated with grooming behavior. Compared to controls, AS increased immobility behavior and P-Ng and Ng levels in the hippocampus and prefrontal cortex. In AS animals, immobility behavior was positively correlated with the P-Ng in the prefrontal cortex. Thus, CS and AS produced opposing effects on Ng and P-Ng levels in the hippocampus and prefrontal cortex. Low Ng levels in the hippocampus were associated with anhedonic behavior in CS animals, whereas high P-Ng levels in the prefrontal cortex were associated with anxiety-like behavior in AS animals. Thus, Ng dysfunction might contribute to the neural mechanisms underlying stress-induced depression and anxiety.展开更多
基金Supported by the Youth Top Talent Project of Fujian Province,China“Young Eagle Project”(No.2901-750102003)。
文摘Background:Vascular cognitive impairment caused by chronic cerebral hypoperfusion(CCH)has become a hot issue worldwide.Aerobic exercise positively contributes to the preservation or restoration of cognitive abilities;however,the specific mechanism has remained inconclusive.And recent studies found that neurogranin(Ng)is a potential biomarker for cognitive impairment.This study aims to investigate the underlying role of Ng in swimming training to improve cognitive impairment.Methods:To test this hypothesis,the clustered regularly interspaced short palindromic repeats(CRISPR)-associated protein 9(Cas9)system was utilized to construct a strain of Ng conditional knockout(Ng cKO)mice,and bilateral common carotid artery stenosis(BCAS)surgery was performed to prepare the model.In Experiment 1,2-month-old male and female transgenic mice were divided into a control group(wild-type littermate,n=9)and a Ng cKO group(n=9).Then,2-month-old male and female C57BL/6 mice were divided into a sham group(C57BL/6,n=12)and a BCAS group(n=12).In Experiment 2,2-month-old male and female mice were divided into a sham group(wild-type littermate,n=12),BCAS group(n=12),swim group(n=12),BCAS+Ng cKO group(n=12),and swim+Ng cKO group(n=12).Then,7 days after BCAS,mice were given swimming training for 5 weeks(1 week for adaptation and 4 weeks for training,5 days a week,60 min a day).After intervention,laser speckle was used to detect cerebral blood perfusion in the mice,and the T maze and Morris water maze were adopted to test their spatial memory.Furthermore,electrophysiology and Western blotting were conducted to record long-term potential and observe the expressions of Ca^(2+)pathway-related proteins,respectively.Immunohistochemistry was applied to analyze the expression of relevant markers in neuronal damage,inflammation,and white matter injury.Results:The figures showed that spatial memory impairment was detected in Ng cKO mice,and a sharp decline of cerebral blood flow and an impairment of progressive spatial memory were observed in BCAS mice.Regular swimming training improved the spatial memory impairment of BCAS mice.This was achieved by preventing long-term potential damage and reversing the decline of Ca^(2+)signal transduction pathway-related proteins.At the same time,the results suggested that swimming also led to improvements in neuronal death,inflammation,and white matter injury induced by CCH.Further study adopted the use of Ng cKO transgenic mice,and the results indicated that the positive effects of swimming training on cognitive impairments,synaptic plasticity,and related pathological changes caused by CCH could be abolished by the knockout of Ng.Conclusion:Swimming training can mediate the expression of Ng to enhance hippocampal synaptic plasticity and improve related pathological changes induced by CCH,thereby ameliorating the spatial memory impairment of vascular cognitive impairment.
文摘Here we tested the hypothesis that stress-induced alterations in Neurogranin (Ng) synthesis and/ or utilization might underlie stress-related depression and anxiety. Rats were randomly divided into five conditions: chronic swim stress (CS), acute swim stress (AS), and three control groups. The CS group was exposed to daily swim stress (5 min/day) for 14 consecutive days, the AS group received a single swim stress, and control groups were maintained in a stress-free condition. Both before and after swim stress, rats were tested for body weight gain, open-field locomotor activity, and saccharine preference. Ng and phospho-Ng (P-Ng) levels in the hippocampus and prefrontal cortex were determined by Western blot analysis. Compared to controls, CS animals displayed significantly decreased body weight gain, ambulation, and saccharine intake, and increased grooming behavior. CS animals had decreased Ng levels in the hippocampus and prefrontal cortex. In CS animals, Ng levels were positively correlated with saccharine intake and ambulation, and inversely correlated with grooming behavior. Compared to controls, AS increased immobility behavior and P-Ng and Ng levels in the hippocampus and prefrontal cortex. In AS animals, immobility behavior was positively correlated with the P-Ng in the prefrontal cortex. Thus, CS and AS produced opposing effects on Ng and P-Ng levels in the hippocampus and prefrontal cortex. Low Ng levels in the hippocampus were associated with anhedonic behavior in CS animals, whereas high P-Ng levels in the prefrontal cortex were associated with anxiety-like behavior in AS animals. Thus, Ng dysfunction might contribute to the neural mechanisms underlying stress-induced depression and anxiety.
文摘为探讨慢性情绪应激、生理应激对大鼠旷场行为和脑神经颗粒素(Neurogran in,NG)含量的不同作用,以及NG含量变化与应激性行为效应之间的相互关系。分别以不确定性空瓶刺激和饮水剥夺,建立情绪应激和生理应激动物模型。将40只雄性SD大鼠随机分为情绪应激组(ES)、生理应激组(PS)、定时饮水组(C1)和正常对照组(C2)(n=10)。以旷场行为任务来评定大鼠应激后的行为变化,W estern b lotting方法测定海马和前脑皮层中的NG含量。结果表明:应激后四组大鼠海马的NG含量差异无显著性;ES组前脑皮层的NG含量低于C2组,差异具有显著性,p<0.01;PS组的前脑皮层NG含量也下降,但与C2组相比差异无显著性;应激后ES组、PS组修饰行为多于C2组,差异具有显著性,分别为p<0.01,p<0.05;前脑皮层NG含量与修饰行为之间的相关达显著水平。提示慢性情绪和生理应激均能导致前脑皮层NG含量下降,修饰行为增加,情绪应激作用更显著。修饰行为可能是反映情绪状态的较敏感行为指标,前脑皮层NG水平可能是预测情绪应激所致焦虑或抑郁行为的较敏感生物学指标。
