Mitochondrial dysfunction is a hallmark of Alzheimer’s disease.We previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of AP P/PS1 mice.Because Alzheime...Mitochondrial dysfunction is a hallmark of Alzheimer’s disease.We previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of AP P/PS1 mice.Because Alzheimer’s disease affects the entire brain,further research is needed to elucidate alterations in mitochondrial metabolism in the brain as a whole.Here,we investigated the expression of several important mitochondrial biogenesis-related cytokines in multiple brain regions after treatment with neural stem cell-derived exosomes and used a combination of whole brain clearing,immunostaining,and lightsheet imaging to clarify their spatial distribution.Additionally,to clarify whether the sirtuin 1(SIRT1)-related pathway plays a regulatory role in neural stem cell-de rived exosomes interfering with mitochondrial functional changes,we generated a novel nervous system-SIRT1 conditional knoc kout AP P/PS1mouse model.Our findings demonstrate that neural stem cell-de rived exosomes significantly increase SIRT1 levels,enhance the production of mitochondrial biogenesis-related fa ctors,and inhibit astrocyte activation,but do not suppress amyloid-βproduction.Thus,neural stem cell-derived exosomes may be a useful therapeutic strategy for Alzheimer’s disease that activates the SIRT1-PGC1αsignaling pathway and increases NRF1 and COXIV synthesis to improve mitochondrial biogenesis.In addition,we showed that the spatial distribution of mitochondrial biogenesis-related factors is disrupted in Alzheimer’s disease,and that neural stem cell-derived exosome treatment can reverse this effect,indicating that neural stem cell-derived exosomes promote mitochondrial biogenesis.展开更多
The number of people with Alzheimer’s disease(AD)is increasing annually,with the nidus mainly concentrated in the cortex and hippocampus.Despite of numerous efforts,effective treatment of AD is still facing great cha...The number of people with Alzheimer’s disease(AD)is increasing annually,with the nidus mainly concentrated in the cortex and hippocampus.Despite of numerous efforts,effective treatment of AD is still facing great challenges due to the blood brain barrier(BBB)and limited drug distribution in the AD nidus sites.Thus,in this study,using vinpocetine(VIN)as a model drug,the objective is to explore the feasibility of tackling the above bottleneck via intranasal drug delivery in combination with a brain guider,borneol(BOR),using nanoemulsion(NE)as the carrier.First of all,the NE were prepared and characterized.In vivo behavior of the NE after intranasal administration was investigated.Influence of BOR dose,BOR administration route on drug brain targeting behavior was evaluated,and the influence of BOR addition on drug brain subregion distribution was probed.It was demonstrated that all the NE had comparable size and similar retention behavior after intranasal delivery.Compared to intravenous injection,improved brain targeting effect was observed by intranasal route,and drug targeting index(DTI)of the VIN–NE group was 154.1%,with the nose-to-brain direct transport percentage(DTP)35.1%.Especially,remarkably enhanced brain distribution was achieved after BOR addition in the NE,with the extent depending on BOR dose.VIN brain concentration was the highest in the VIN-1-BOR-NE group at BOR dose of 1 mg/kg,with the DTI reaching 596.1%and the DTP increased to 83.1%.BOR could exert better nose to brain delivery when administrated together with the drug via intranasal route.Notably,BOR can remarkably enhance drug distribution in both hippocampus and cortex,the nidus areas of AD.In conclusion,in combination with intranasal delivery and the intrinsic brain guiding effect of BOR,drug distribution not only in the brain but also in the cortex and hippocampus can be enhanced significantly,providing the perquisite for improved therapeutic efficacy of AD.展开更多
BACKGROUND: The implantation of released chemotherapeutic drugs, which takes biodegradable polymer as vector, into the tumor site can get high concentration and release the drug for a long time, it can directly act on...BACKGROUND: The implantation of released chemotherapeutic drugs, which takes biodegradable polymer as vector, into the tumor site can get high concentration and release the drug for a long time, it can directly act on the tumor cells, and reduce the general toxicity. OBJECTIVE: To explore the in vitro and in vivo course of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) sustained-release from BCNU-loaded polylactide (PLA) microspheres (MS) and location in rat brain tissue. DESIGN: A repetitive measurement. SETTING:Central Pharmacy, General Hospital of Chinese People’s Armed Police Forces. MATERIALS: Thirty male SD rats were used. PLA (Mr5000, batch number: KSL8377) was produced by Wako Pure Chemical Inc.,Ltd. (Japan); BCNU (batch number: 021121) by Tianjin Jinyao Amino Acid Co., Ltd.; BCNU-PLA-MS was prepared by the method of solvent evaporation and pressed into tablets (10 mg/tablet). High-performance liquid chromatography (HPLC) Agilent 1100 (USA); LS9800 liquid-scintillation radiometric apparatus (Beckman). Chromatographic conditions: Elite Hypersil ODS2 C18 chromatographic column (5 μm, 4.6 mm×150 mm); Mobile phase: methanol: water (50:50), flow rate was 1.0 mL per minute, wave length of ultraviolet detection was 237 nm, and the inlet amount of samples was 10 μL. METHODS: The experiments were carried out in the experimental animal center of the General Hospital of Chinese Armed Police from May 2004 to July 2005. ① In vitro BCNU-PLA-MS release test: BCNU-PLA-MS was prepared by the method of solvent evaporation, then placed in 0.1 mol/L phosphate buffered solution (PBS, pH 7.4, 37 ℃), part of MS were taken out at 1, 2, 3, 7, 10 and 15 days respectively, and the rest amount of BCNU in MS was determined by HPLC, then the curve of BCNU-PLA-MS release was drawn. ②In vivo BCNU-PLA-MS release and distribution test: The rats were anesthetized, then BCNU-PLA-MS were implanted to the site 1 mm inferior to the cortex of frontal lobe. Five rats were killed postoperatively at 4 hours, 1, 2, 3, 7 and 15 days, the residual MS was removed from the brain tissue. The rest amount of BCNU was determined with HLPC, and the curve of BCNU-PLA-MS release was drawn as compared with the amount of BCNU in the implanted tablets. Besides, brain tissues (1 g) at the implanted side and the contralateral one were obtained respectively, blood sample (0.5 mL) was also collected, 3H-BCNU was counted radioactively in radioactive liquid flash solution. The distributions of BCNU-PLA-MS in normal rat brain tissue and serum were detected. The analysis of variance was applied to compare the intergroup differences of the measurement data. MAIN OUTCOME MEASURES: ① Characteristics of BCNU-PLA-MS release in phosphate buffered solution (PBS) and rat brain tissue; ② Distributions of BCNU-PLA-MS in normal rat brain tissue and serum. RESULTS: ① Release of BCNU-PLA-MS in PBS and rat brain tissue: The BCNU released from BCNU-PLA-MS could be sustained for over 2 weeks both in PBS and brain tissue. In PBS, the released rate of BCNU was over 15% at 24 hours, nearly 50% at 72 hours and over 90% at 15 days. In brain tissue, the released rate was 8% at 4 hours, 16% at 24 hours, 60% at 72 hours, respectively, and BCNU could be sustained released for over 15 days. ② Distributions of BCNU-PLA-MS in normal rat brain tissue and serum: The concentrations of BCNU in the ipsilateral brain tissue were 6 to 70 times higher than those in the contralateral one. The concentrations of BCNU in the ipsilateral brain tissue were obviously higher than those in serum and contralateral brain tissue (F =103.47, P < 0.01). CONCLUSION: BCNU-PLA-MS can increase the drug concentration in targeted brain tissue, decrease that in the non-targeted brain tissue, reduce general toxic and side effects, and have good releasing function.展开更多
BACKGROUND： Elk-1 mRNA distributes extensively in the neurons of mice, rat and human brains, and the Elk-1 expression may be correlated with the synaptic plasticity, learning and memory. OBJECTIVE： To observe the di...BACKGROUND： Elk-1 mRNA distributes extensively in the neurons of mice, rat and human brains, and the Elk-1 expression may be correlated with the synaptic plasticity, learning and memory. OBJECTIVE： To observe the distribution of phosphorylated Elk-1 （pEIk-1） in whole brain of rats received Y-maze active avoidance training and the changes of pEIk-1 expression at different time points after training. DESIGN ： A randomized controlled study SETTING ： Research Room of Neurobiology, the Second Affiliated Hospital of Southern Medical University MATERIALS ： Fifty-five male clean-degree SD rats of 3-4 months old, weighing 200-250 g, were provided by the Experimental Animal Center of Southem Medical University. The rabbit anti-monoclonal pEIk-1 antibody was purchased from Cell Signal Transduction Company, and ABC kit from Vector Company. METHODS ： The experiments were carried out in the Research Room of Neurobiology, Second Affiliated Hospital of Southern Medical University from September 2004 to February 2005. ① Grouping： The rats were randomly divided into training group （n = 25）, sham-training group （n = 25） and normal control group （n = 5）, and the training and sham-training groups were observed at 0, 1, 3, 6 and 24 hours after training, which represented the five phases in the process of leaming and memory. ② Y-maze training： The rats were preconditioned in the electrical Y-maze apparatus, 20 minutes a day for 3 days continuously, and training began from the 4^th day. In the training group, the rats were trained with the combination of light and electddty. Each rat repeated for 60 times in each training, and the correct times were recorded, those correct for less than 25 times were taken as unqualified, and excluded from the training group, and supplemented by other rats in time. In the sham-training group, there was no fixed correlation between the application of light and electricity. The rats in the normal contrel group were given not any training. ③Detection of pEIk-1 expression： The rats were anesthetized after Y-maze training, brain tissue was removed to prepare coronal freezing sections, and the pEIk-1 expression was detected with routine ABC method. MATN OUTCOME MEASURES： ① Distribution of pEIk-1 immuno-positive neurons in whole brain of rats in the normal control group. ②Comparison of the expression of pEIk-1 immuno-positive neurons in whole brain at different time points after training between the training group and sham-training group. RESULTS ： All the 55 rats were involved in result analysis. ③ Distribution of pEIk-1 immuno-positive neurons in the whole brain of rats in the normal control group： Strong expressions of pEIk-1 immuno-positive neurons were observed in prefrontal lobe, granular layer of olfactory bulbs, Purkinje cell layer and granular layer of cerebellum, whole stdate cortex, temporal cortex, pre-pyriform cortex, hypothalamic supraoptic nucleus, hypothalamic paraventricular nucleus and periventricular nucleus, thalamic paraventricular nucleus, pronucleus and postnucleus of amygdala cortex, central nucleus of amygdala, medial amygdaloid nucleus, entorhinal cortex, hippocampal dentate gyros, CA1-4 regions, caudate-putamen, material division, brain stem spinal nucleus of trigeminal nerve, and superior olivary nucleus, and those in hippocampal dentate gyrus and CA1 region were the strongest.② Distribution of pEIk-1 immuno-positive neurons in the whole brain of rats at different time points after training in the training group and sham-training group： In the training group, the expressions were obviously enhanced in caudate-putamen of striatum, material division, most cortexes, hippocampal dentate gyrus, hippocampal CA regions, nucleus amygdalae, thalamic paraventricular nucleus, Purkinje cell layer of cerebellum, entorhinal cortex, hypothalamic supraoptic nucleus, hypothalamic paraventricular nucleus, and periventricular nucleus at 0 hour after training, and the enhancement lasted for 6 hours at least, and those at 24 hours were decreased to normal. In the sham-training group, obvious enhanced expressions of pEIk-1 immuno-positive neurons could be observed in most cortexes, nucleus amygdalae, entorhinal cortex, hypothalamic supraoptic nucleus, hypothalamic paraventdoular nucleus and periventricular nucleus, brain stem spinal nucleus of trigeminal nerve, Purkinje cell layer and granular layer of cerebellum at O, 1, 3 and 6 hours, and decreased to normal after 24 hours. The expressions in material division, caudate-putamen of striatum, hippocampus were not obviously enhanced as compared with those in the normal control group, but significantly different from those in the training group （0, 1, 3, 6 hours after training, material division： F= 0.576, 0.023, 0.116, 8.873, P〈 0.01; caudate-putamen： F= 0.157, 0.427, 0.030, 0.001, P〈 0.01; hippocampus： F= 6.716, 2.405, 14.137, 1.416, P 〈 0.05-0.01 ）. CONCLUSION： The expression of activated pEIk-1 can be detected in the learning related brain areas under normal status, and the perk-1 expression in the brain areas dynamically changed in a time-dependent manner after Y-maze training, and it is indicated that pEIk-1 is involved in the learning and memory process in Y-maze related brain areas.展开更多
Measurement of oxygen concentration and distribution in brain is essential to understanding the pathophysiology of stroke. Although brain oxygen level is critical for brain tissue survival,
N-Methyl-D-aspartate receptors（NMDARs） play vital roles in the central nervous system,as they are primary mediators of Ca2＋influx during synaptic activity.The subunits that compose NMDARs share similar topological ...N-Methyl-D-aspartate receptors（NMDARs） play vital roles in the central nervous system,as they are primary mediators of Ca2＋influx during synaptic activity.The subunits that compose NMDARs share similar topological structures but are distinct in distribution and pharmacological properties,as well as physiological and pathological functions,which make the NMDAR one of the most complex and elusive ionotropic glutamate receptors.In this review,we focus on GluN2A and GluN2B,the primary NMDAR subunits in the cortex and hippocampus,and discuss their differences in developmental expression,brain distribution,trafficking,and functional properties during neuronal activity.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82171194 and 81974155(both to JL)the Shanghai Municipal Science and Technology Commission Medical Guide Project,No.16411969200(to WZ)Shanghai Municipal Science and Technology Commission Biomedical Science and Technology Project,No.22S31902600(to JL)。
文摘Mitochondrial dysfunction is a hallmark of Alzheimer’s disease.We previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of AP P/PS1 mice.Because Alzheimer’s disease affects the entire brain,further research is needed to elucidate alterations in mitochondrial metabolism in the brain as a whole.Here,we investigated the expression of several important mitochondrial biogenesis-related cytokines in multiple brain regions after treatment with neural stem cell-derived exosomes and used a combination of whole brain clearing,immunostaining,and lightsheet imaging to clarify their spatial distribution.Additionally,to clarify whether the sirtuin 1(SIRT1)-related pathway plays a regulatory role in neural stem cell-de rived exosomes interfering with mitochondrial functional changes,we generated a novel nervous system-SIRT1 conditional knoc kout AP P/PS1mouse model.Our findings demonstrate that neural stem cell-de rived exosomes significantly increase SIRT1 levels,enhance the production of mitochondrial biogenesis-related fa ctors,and inhibit astrocyte activation,but do not suppress amyloid-βproduction.Thus,neural stem cell-derived exosomes may be a useful therapeutic strategy for Alzheimer’s disease that activates the SIRT1-PGC1αsignaling pathway and increases NRF1 and COXIV synthesis to improve mitochondrial biogenesis.In addition,we showed that the spatial distribution of mitochondrial biogenesis-related factors is disrupted in Alzheimer’s disease,and that neural stem cell-derived exosome treatment can reverse this effect,indicating that neural stem cell-derived exosomes promote mitochondrial biogenesis.
基金supported by the Distinguished Professor Project of Liaoning Province.
文摘The number of people with Alzheimer’s disease(AD)is increasing annually,with the nidus mainly concentrated in the cortex and hippocampus.Despite of numerous efforts,effective treatment of AD is still facing great challenges due to the blood brain barrier(BBB)and limited drug distribution in the AD nidus sites.Thus,in this study,using vinpocetine(VIN)as a model drug,the objective is to explore the feasibility of tackling the above bottleneck via intranasal drug delivery in combination with a brain guider,borneol(BOR),using nanoemulsion(NE)as the carrier.First of all,the NE were prepared and characterized.In vivo behavior of the NE after intranasal administration was investigated.Influence of BOR dose,BOR administration route on drug brain targeting behavior was evaluated,and the influence of BOR addition on drug brain subregion distribution was probed.It was demonstrated that all the NE had comparable size and similar retention behavior after intranasal delivery.Compared to intravenous injection,improved brain targeting effect was observed by intranasal route,and drug targeting index(DTI)of the VIN–NE group was 154.1%,with the nose-to-brain direct transport percentage(DTP)35.1%.Especially,remarkably enhanced brain distribution was achieved after BOR addition in the NE,with the extent depending on BOR dose.VIN brain concentration was the highest in the VIN-1-BOR-NE group at BOR dose of 1 mg/kg,with the DTI reaching 596.1%and the DTP increased to 83.1%.BOR could exert better nose to brain delivery when administrated together with the drug via intranasal route.Notably,BOR can remarkably enhance drug distribution in both hippocampus and cortex,the nidus areas of AD.In conclusion,in combination with intranasal delivery and the intrinsic brain guiding effect of BOR,drug distribution not only in the brain but also in the cortex and hippocampus can be enhanced significantly,providing the perquisite for improved therapeutic efficacy of AD.
文摘BACKGROUND: The implantation of released chemotherapeutic drugs, which takes biodegradable polymer as vector, into the tumor site can get high concentration and release the drug for a long time, it can directly act on the tumor cells, and reduce the general toxicity. OBJECTIVE: To explore the in vitro and in vivo course of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) sustained-release from BCNU-loaded polylactide (PLA) microspheres (MS) and location in rat brain tissue. DESIGN: A repetitive measurement. SETTING:Central Pharmacy, General Hospital of Chinese People’s Armed Police Forces. MATERIALS: Thirty male SD rats were used. PLA (Mr5000, batch number: KSL8377) was produced by Wako Pure Chemical Inc.,Ltd. (Japan); BCNU (batch number: 021121) by Tianjin Jinyao Amino Acid Co., Ltd.; BCNU-PLA-MS was prepared by the method of solvent evaporation and pressed into tablets (10 mg/tablet). High-performance liquid chromatography (HPLC) Agilent 1100 (USA); LS9800 liquid-scintillation radiometric apparatus (Beckman). Chromatographic conditions: Elite Hypersil ODS2 C18 chromatographic column (5 μm, 4.6 mm×150 mm); Mobile phase: methanol: water (50:50), flow rate was 1.0 mL per minute, wave length of ultraviolet detection was 237 nm, and the inlet amount of samples was 10 μL. METHODS: The experiments were carried out in the experimental animal center of the General Hospital of Chinese Armed Police from May 2004 to July 2005. ① In vitro BCNU-PLA-MS release test: BCNU-PLA-MS was prepared by the method of solvent evaporation, then placed in 0.1 mol/L phosphate buffered solution (PBS, pH 7.4, 37 ℃), part of MS were taken out at 1, 2, 3, 7, 10 and 15 days respectively, and the rest amount of BCNU in MS was determined by HPLC, then the curve of BCNU-PLA-MS release was drawn. ②In vivo BCNU-PLA-MS release and distribution test: The rats were anesthetized, then BCNU-PLA-MS were implanted to the site 1 mm inferior to the cortex of frontal lobe. Five rats were killed postoperatively at 4 hours, 1, 2, 3, 7 and 15 days, the residual MS was removed from the brain tissue. The rest amount of BCNU was determined with HLPC, and the curve of BCNU-PLA-MS release was drawn as compared with the amount of BCNU in the implanted tablets. Besides, brain tissues (1 g) at the implanted side and the contralateral one were obtained respectively, blood sample (0.5 mL) was also collected, 3H-BCNU was counted radioactively in radioactive liquid flash solution. The distributions of BCNU-PLA-MS in normal rat brain tissue and serum were detected. The analysis of variance was applied to compare the intergroup differences of the measurement data. MAIN OUTCOME MEASURES: ① Characteristics of BCNU-PLA-MS release in phosphate buffered solution (PBS) and rat brain tissue; ② Distributions of BCNU-PLA-MS in normal rat brain tissue and serum. RESULTS: ① Release of BCNU-PLA-MS in PBS and rat brain tissue: The BCNU released from BCNU-PLA-MS could be sustained for over 2 weeks both in PBS and brain tissue. In PBS, the released rate of BCNU was over 15% at 24 hours, nearly 50% at 72 hours and over 90% at 15 days. In brain tissue, the released rate was 8% at 4 hours, 16% at 24 hours, 60% at 72 hours, respectively, and BCNU could be sustained released for over 15 days. ② Distributions of BCNU-PLA-MS in normal rat brain tissue and serum: The concentrations of BCNU in the ipsilateral brain tissue were 6 to 70 times higher than those in the contralateral one. The concentrations of BCNU in the ipsilateral brain tissue were obviously higher than those in serum and contralateral brain tissue (F =103.47, P < 0.01). CONCLUSION: BCNU-PLA-MS can increase the drug concentration in targeted brain tissue, decrease that in the non-targeted brain tissue, reduce general toxic and side effects, and have good releasing function.
文摘BACKGROUND： Elk-1 mRNA distributes extensively in the neurons of mice, rat and human brains, and the Elk-1 expression may be correlated with the synaptic plasticity, learning and memory. OBJECTIVE： To observe the distribution of phosphorylated Elk-1 （pEIk-1） in whole brain of rats received Y-maze active avoidance training and the changes of pEIk-1 expression at different time points after training. DESIGN ： A randomized controlled study SETTING ： Research Room of Neurobiology, the Second Affiliated Hospital of Southern Medical University MATERIALS ： Fifty-five male clean-degree SD rats of 3-4 months old, weighing 200-250 g, were provided by the Experimental Animal Center of Southem Medical University. The rabbit anti-monoclonal pEIk-1 antibody was purchased from Cell Signal Transduction Company, and ABC kit from Vector Company. METHODS ： The experiments were carried out in the Research Room of Neurobiology, Second Affiliated Hospital of Southern Medical University from September 2004 to February 2005. ① Grouping： The rats were randomly divided into training group （n = 25）, sham-training group （n = 25） and normal control group （n = 5）, and the training and sham-training groups were observed at 0, 1, 3, 6 and 24 hours after training, which represented the five phases in the process of leaming and memory. ② Y-maze training： The rats were preconditioned in the electrical Y-maze apparatus, 20 minutes a day for 3 days continuously, and training began from the 4^th day. In the training group, the rats were trained with the combination of light and electddty. Each rat repeated for 60 times in each training, and the correct times were recorded, those correct for less than 25 times were taken as unqualified, and excluded from the training group, and supplemented by other rats in time. In the sham-training group, there was no fixed correlation between the application of light and electricity. The rats in the normal contrel group were given not any training. ③Detection of pEIk-1 expression： The rats were anesthetized after Y-maze training, brain tissue was removed to prepare coronal freezing sections, and the pEIk-1 expression was detected with routine ABC method. MATN OUTCOME MEASURES： ① Distribution of pEIk-1 immuno-positive neurons in whole brain of rats in the normal control group. ②Comparison of the expression of pEIk-1 immuno-positive neurons in whole brain at different time points after training between the training group and sham-training group. RESULTS ： All the 55 rats were involved in result analysis. ③ Distribution of pEIk-1 immuno-positive neurons in the whole brain of rats in the normal control group： Strong expressions of pEIk-1 immuno-positive neurons were observed in prefrontal lobe, granular layer of olfactory bulbs, Purkinje cell layer and granular layer of cerebellum, whole stdate cortex, temporal cortex, pre-pyriform cortex, hypothalamic supraoptic nucleus, hypothalamic paraventricular nucleus and periventricular nucleus, thalamic paraventricular nucleus, pronucleus and postnucleus of amygdala cortex, central nucleus of amygdala, medial amygdaloid nucleus, entorhinal cortex, hippocampal dentate gyros, CA1-4 regions, caudate-putamen, material division, brain stem spinal nucleus of trigeminal nerve, and superior olivary nucleus, and those in hippocampal dentate gyrus and CA1 region were the strongest.② Distribution of pEIk-1 immuno-positive neurons in the whole brain of rats at different time points after training in the training group and sham-training group： In the training group, the expressions were obviously enhanced in caudate-putamen of striatum, material division, most cortexes, hippocampal dentate gyrus, hippocampal CA regions, nucleus amygdalae, thalamic paraventricular nucleus, Purkinje cell layer of cerebellum, entorhinal cortex, hypothalamic supraoptic nucleus, hypothalamic paraventricular nucleus, and periventricular nucleus at 0 hour after training, and the enhancement lasted for 6 hours at least, and those at 24 hours were decreased to normal. In the sham-training group, obvious enhanced expressions of pEIk-1 immuno-positive neurons could be observed in most cortexes, nucleus amygdalae, entorhinal cortex, hypothalamic supraoptic nucleus, hypothalamic paraventdoular nucleus and periventricular nucleus, brain stem spinal nucleus of trigeminal nerve, Purkinje cell layer and granular layer of cerebellum at O, 1, 3 and 6 hours, and decreased to normal after 24 hours. The expressions in material division, caudate-putamen of striatum, hippocampus were not obviously enhanced as compared with those in the normal control group, but significantly different from those in the training group （0, 1, 3, 6 hours after training, material division： F= 0.576, 0.023, 0.116, 8.873, P〈 0.01; caudate-putamen： F= 0.157, 0.427, 0.030, 0.001, P〈 0.01; hippocampus： F= 6.716, 2.405, 14.137, 1.416, P 〈 0.05-0.01 ）. CONCLUSION： The expression of activated pEIk-1 can be detected in the learning related brain areas under normal status, and the perk-1 expression in the brain areas dynamically changed in a time-dependent manner after Y-maze training, and it is indicated that pEIk-1 is involved in the learning and memory process in Y-maze related brain areas.
文摘Measurement of oxygen concentration and distribution in brain is essential to understanding the pathophysiology of stroke. Although brain oxygen level is critical for brain tissue survival,
基金supported by grants from the National Basic Research Development Program of China(2010CB912002)the National Natural Science Foundation of China(30730038 and 81171164)
文摘N-Methyl-D-aspartate receptors（NMDARs） play vital roles in the central nervous system,as they are primary mediators of Ca2＋influx during synaptic activity.The subunits that compose NMDARs share similar topological structures but are distinct in distribution and pharmacological properties,as well as physiological and pathological functions,which make the NMDAR one of the most complex and elusive ionotropic glutamate receptors.In this review,we focus on GluN2A and GluN2B,the primary NMDAR subunits in the cortex and hippocampus,and discuss their differences in developmental expression,brain distribution,trafficking,and functional properties during neuronal activity.
