BACKGROUND： Previous studies have demonstrated that postsynaptic density protein-95 （PSD-95） is widely distributed in the central nervous system and is related to the development of the CNS and sensory signal trans...BACKGROUND： Previous studies have demonstrated that postsynaptic density protein-95 （PSD-95） is widely distributed in the central nervous system and is related to the development of the CNS and sensory signal transmission as well as acute or chronic nerve cell death following ischemic brain injury. OBJECTIVE： To semi-quantitatively determine the pathological changes of apoptotic facial neurons and the expression of PSD-95 in the facial nucleus following facial nerve injury of varying extents using immunohistochemical staining methods. DESIGN, TIME AND SETTING： Randomized, controlled animal experiments were performed in the Ultrasonic Institute of the Second Affiliated Hospital of Chongqing University of Medical Sciences from September to December 2007. MATERIALS： Sixty-five healthy, adult, Sprague-Dawley （SD） rats, both male and female, were used for this study. Rabbit anti-rat PSD-95 polyclonal antibody was purchased from Beijing Biosynthesis Biotechnology Co., Ltd. METHODS： SD rats were randomly assigned into a control group with five rats and three injured groups with 20 rats per group. Exposure, clamp and cut for bilateral facial nerve trunks were performed in the rats of the injury groups, and no injury was inflicted on the rats of the control group. MAIN OUTCOME MEASURES; The brainstems of all the rats were excised on days 1, 3, 7, and 14 post injury, and then the facial nuclei were stained with hematoxylin-eosin to observe any pathological changes due to apoptosis in facial neurons. PSD-95 expression in facial nuclei was detected by immunohistochemistry and the number of PSD-95 positive cells was counted under a light microscope. RESULTS： The expression of PSD-95 in the facial nucleus and morphology of the facial neuron within the exposure group had no obvious changes at various points in time tested （P 〉 0.05）. However, the expressions of PSD-95 in the facial nucleus of the clamp group and cut group increased on day 1 post injury （P 〈 0.05）, and showed further increase on day 7 post injury （P 〈 0.01 ）. This did not decrease until day 14 post injury. Facial neuron apoptosis was detected on day 3 post injury and this was even more obvious on day 7 and was maintained to day 14 post injury. The number of cells expressing PSD-95 and displaying severe degrees of facial neuron apoptosis were as follows： cut group 〉 clamp group 〉 exposure group. CONCLUSION： The apoptotic extent of facial neurons and the expression of PSD-95 in apoptotic facial neurons increased with the degree of aggravation of injured severity of facial nerve.展开更多
Objective Postsynaptic density protein 95 （PSD-95） plays important roles in the regulation of glutamate signaling, such as that of N-methyl-D-aspartate receptors （NMDARs）. In this study, the functional roles of PS...Objective Postsynaptic density protein 95 （PSD-95） plays important roles in the regulation of glutamate signaling, such as that of N-methyl-D-aspartate receptors （NMDARs）. In this study, the functional roles of PSD-95 in tyrosine phosphorylafion of NMDAR subunit 2A （NR2A） and in apoptosis-like cell death induced by oxygen-glucose de- privation （OGD） in cultured rat cortical neurons were investigated. Methods We used immunoprecipitation and immuno- blotting to detect PSD-95 protein level, tyrosine phosphorylation level of NR2A, and the interaction between PSD-95 and NR2A or Src. Apoptosis-like cells were observed by 4,6-diamidino-2-phenylindole staining. Results Tyrosine phospho- rylation of NR2A and apoptosis-like cell death were increased after recovery following 60-min OGD. The increases were attenuated by pretreatment with antisense oligonucleotides against PSD-95 before OGD, but not by missense oligonucle- otides or vehicle. PSD-95 antisense oligonucleotides also inhibited the increased interaction between PSD-95 and NR2A or Src, while NR2A expression did not change under this condition. Conclusion PSD-95 may be involved in regulating NR2A tyrosine phosphorylation by Src kinase. Inhibition of PSD-95 expression can be neuroprotective against apoptosis- like cell death after recovery from OGD.展开更多
BACKGROUND： The change in expression of synaptophysin （Syp） and postsynaptic density-95 （PSD-95） alters after cerebral infarction, and the plasticity of synapses contributes greatly to nerve function recovery. Ch...BACKGROUND： The change in expression of synaptophysin （Syp） and postsynaptic density-95 （PSD-95） alters after cerebral infarction, and the plasticity of synapses contributes greatly to nerve function recovery. Chinese medicinal substances may play an important role in the expression of Syp and PSD-95. OBJECTIVE： To observe the effect of Panaxtriol Saponins （PTS）, an active component in Sanqi tongshu capsules, on the expression of Syp and PSD-95 after cerebral infarction at different time points in rats, so as to examine the cerebral function remodeling mechanism. DESIGN, TIME AND SETTING： A randomized and controlled observation which was performed in Dongzhimen Hospital, Beijing University of Traditional Chinese Medicine from January to March, 2007. MATERIALS： Twenty-six healthy male Sprague Dawley rats were used to establish middle cerebral artery occlusion based on the Longa method. Sanqi tongshu capsules （containing 100 mg PTS per tablet） were provided by the Chengdu Huashen Group and nimodipine tablets （30 mg） by Tianjin Zhongyang Pharmaceutical Co., Ltd. METHODS： Twenty-six rats were randomly divided into an operation group （n = 21 ） and a control group （n = 5）. The operation group underwent the EZ Longa procedure to make the middle cerebral artery occlusion model. After surgery rats were randomly divided into a model group, a PTS group and a nimodipine group, with seven rats in each group. Rats were intragastrically administrated with saline （2 mL/d） in the model group, with Sanqi tongshu capsule （5.4 mg/100 g/d） in the PTS group, and with nimodipine （1.73 mg/100 g/d） in the nimodipine group. Rats in the control group did not undergo model establishment and drug administration. MAIN OUTCOME MEASURES： The expressions of Syp and PSD-95 were measured by immunohistochemical and image analysis at days 3, 7 and 28 after the operation. RESULTS： The expression of Syp and PSD-95 in the operation group was significantly lower than in the control group at days 3, 7, 28 postoperatively （P 〈 0.05）. The expression of Syp and PSD-95 in the PTS group and nimodipine group was significantly higher than in the model group at day 28 postoperatively （P 〈 0.05-0.01）. Additionally, after PTS and nimodipine treatment at different intervals, the expression of Syp and PSD-95 at day 28 postoperatively was significantly higher than those at days 3 and 7 postoperatively, respectively （P 〈 0.01）. CONCLUSION： PTS can promote the expression of Syp and PSD-95, i.e. the remodeling process of synapses, after cerebral infarction at different time points in rats, which contributes to cerebral function remodeling.展开更多
Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at...Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term potentiation.Postsynaptically,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation.In this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression.Treatment with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform.Although TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions.Targeting TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.展开更多
目的:研究三七通舒胶囊有效成分三七三醇皂苷对大鼠脑梗死后不同时点Syp和PSD-95表达的影响,为探讨脑功能重塑的机理提供理论依据。方法:健康雄性SD大鼠,分为手术和正常组,手术组采用改良的Longa方法制备大鼠大脑中动脉阻塞模型,分为模...目的:研究三七通舒胶囊有效成分三七三醇皂苷对大鼠脑梗死后不同时点Syp和PSD-95表达的影响,为探讨脑功能重塑的机理提供理论依据。方法:健康雄性SD大鼠,分为手术和正常组,手术组采用改良的Longa方法制备大鼠大脑中动脉阻塞模型,分为模型组、三七三醇皂苷组和尼莫地平组,于术后3 d、7 d和28 d 3个时间点利用免疫组化及图像分析测定大鼠脑内Syp和PSD-95的表达。结果:术后28 d三七三醇皂苷组和尼莫地平组较模型组的Syp表达上升显著(P<0.01),PSD-95表达上升亦显著(P<0.05和P<0.01),且前两者较自身3 d、7 d Syp和PSD-95表达均有显著升高(P<0.01)。结论:三七三醇皂苷可以促进大鼠脑梗死后不同时点Syp和PSD-95表达,即突触的重塑过程,对大脑功能重塑有积极作用。展开更多
目的检测脑挫伤修复过程中突触后致密蛋白(postsynaptic density protein 95,PSD-95)的表达,探讨其变化规律与损伤时间的相关性。方法雄性SD大鼠50只,随机分为8个实验组,1个对照组,每组5只。制作大鼠脑挫伤模型,于伤后3、6、12h和3、5、...目的检测脑挫伤修复过程中突触后致密蛋白(postsynaptic density protein 95,PSD-95)的表达,探讨其变化规律与损伤时间的相关性。方法雄性SD大鼠50只,随机分为8个实验组,1个对照组,每组5只。制作大鼠脑挫伤模型,于伤后3、6、12h和3、5、7、10d取脑组织,应用免疫组织化学技术和免疫蛋白印迹(Western blot)方法检测脑挫伤后不同时间脑组织中PSD-95的表达变化。结果对照组脑组织仅有少量PSD-95阳性细胞;实验组中,伤后3h、6h组脑组织出现较多PSD-95阳性细胞,12h组阳性细胞数量持续升高,伤后1d阳性细胞数下降,5d后又升高并达到高峰,7d、10d恢复;计算阳性率,统计分析结果显示,阳性细胞数与相邻上组比较,存在显著性差异。Western blot结果:挫伤后,3～12h表达量上升,1d下降,随后又逐步上升,5d达到高峰,7d、10d下降;应用Fluorchem V2.0 Stand Alone软件获取感光条带的平均灰度值,经统计分析,各组与相邻上组比较,存在显著性差异。结论大鼠脑损伤后损伤周边区PSD-95呈现升高→下降→再升高→再下降的表达规律,对损伤时间推断有一定的参考意义。展开更多
目的观察小鼠学习记忆能力及其海马区突触功能相关蛋白脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)、突触后致密蛋白95(postsynaptic density protein 95,PSD95)及GluA1表达的增龄性变化。方法观察10周龄(青年组)和21...目的观察小鼠学习记忆能力及其海马区突触功能相关蛋白脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)、突触后致密蛋白95(postsynaptic density protein 95,PSD95)及GluA1表达的增龄性变化。方法观察10周龄(青年组)和21月龄(老年组)C57BL/6雄性小鼠Morris水迷宫训练和测试表现,并应用Western blot技术检测两组小鼠海马区BDNF、PSD95、GluA1的蛋白表达。结果与青年组相比,老年组小鼠水迷宫测试中的学习记忆能力明显下降(P均<0.05),其海马区总蛋白BDNF、PSD95、GluA1的表达量均显著下降(P均<0.05),海马区膜蛋白GluA1的表达量也明显下降(P<0.05)。结论老年小鼠学习记忆能力下降伴随着海马区突触功能相关蛋白BDNF、PSD95、GluA1表达的一致下降。展开更多
目的探讨戊四氮点燃癫痫对大鼠空间学习记忆的影响及可能的分子机制。方法戊四氮(pentylenetet-razol,PTZ)点燃建立慢性癫痫(chronic epileptic,CEP)模型,Morris水迷宫进行行为学检测,免疫组织化学方法观察大鼠海马CA1、CA3区突触素(syn...目的探讨戊四氮点燃癫痫对大鼠空间学习记忆的影响及可能的分子机制。方法戊四氮(pentylenetet-razol,PTZ)点燃建立慢性癫痫(chronic epileptic,CEP)模型,Morris水迷宫进行行为学检测,免疫组织化学方法观察大鼠海马CA1、CA3区突触素(synaptophysin,P38)和突触后致密物95(postsynaptic density 95,PSD-95)的表达,并用计算机图像分析系统对免疫反应结果进行处理。结果水迷宫试验检测癫痫组大鼠空间学习记忆能力受损;免疫组化结果表明其海马CA1、CA3区P38和PSD-95免疫反应产物较对照组明显减少(P<0.01,P<0.05)。结论戊四氮点燃癫痫大鼠伴有学习记忆功能减退,其海马神经元P38和PSD-95的表达减少可能参与了空间学习记忆受损。展开更多
目的:研究温胆汤对精神分裂症模型大鼠行为学及其海马神经元突触后致密蛋白95(PSD-95)、生长相关蛋白43(GAP-43)、JNK相互作用蛋白3(JIP-3)、连接蛋白43(Cx-43)表达的影响。方法:将SD大鼠随机分为:正常对照组、模型对照组、氯氮平0.02 g...目的:研究温胆汤对精神分裂症模型大鼠行为学及其海马神经元突触后致密蛋白95(PSD-95)、生长相关蛋白43(GAP-43)、JNK相互作用蛋白3(JIP-3)、连接蛋白43(Cx-43)表达的影响。方法:将SD大鼠随机分为:正常对照组、模型对照组、氯氮平0.02 g/kg组、温胆汤10、20、40 g/kg组。正常对照组和模型对照组分别灌胃生理盐水,各组分别灌胃相应药物,1次/d,连续给药21 d。末次给药2 h后,除正常对照组外,其余各组一次性腹腔注射MK-8010.6 mg/kg,以诱发精神分裂症模型。造模后,观察记录各组大鼠的行为学改变和刻板行为评分,旷场实验评价大鼠滞留时间及穿越次数;RT-q PCR法检测大鼠海马组织Psd95、Gap43、Jip3、Cx43 m RNA表达;WB法检测大鼠海马组织PSD-95、GAP-43、JIP-3、Cx-43蛋白表达。结果:与正常对照组比较,模型对照组大鼠刻板行为评分显著升高,在中央区滞留时间及穿越次数显著下降(P<0.01);其海马组织Psd95、Gap43、Jip3、Cx43 m RNA和蛋白表达显著下调(P<0.01);与模型对照组比较,温胆汤10、20、40 g/kg组均能明显降低大鼠刻板行为评分,明显升高中央区滞留时间及穿越频次(P<0.05或P<0.01);能明显上调海马组织Psd95、Gap43、Jip3、Cx43 m RNA和蛋白的表达(P<0.05或P<0.01)。结论:温胆汤可能通过上调PSD-95、GAP-43、JIP-3、Cx-43等突触相关蛋白的表达,从而调控海马神经元突触可塑性,缓解刻板行为和紧张、焦虑等情绪,增强学习和记忆功能,有效改善精神分裂症的认知障碍。展开更多
文摘BACKGROUND： Previous studies have demonstrated that postsynaptic density protein-95 （PSD-95） is widely distributed in the central nervous system and is related to the development of the CNS and sensory signal transmission as well as acute or chronic nerve cell death following ischemic brain injury. OBJECTIVE： To semi-quantitatively determine the pathological changes of apoptotic facial neurons and the expression of PSD-95 in the facial nucleus following facial nerve injury of varying extents using immunohistochemical staining methods. DESIGN, TIME AND SETTING： Randomized, controlled animal experiments were performed in the Ultrasonic Institute of the Second Affiliated Hospital of Chongqing University of Medical Sciences from September to December 2007. MATERIALS： Sixty-five healthy, adult, Sprague-Dawley （SD） rats, both male and female, were used for this study. Rabbit anti-rat PSD-95 polyclonal antibody was purchased from Beijing Biosynthesis Biotechnology Co., Ltd. METHODS： SD rats were randomly assigned into a control group with five rats and three injured groups with 20 rats per group. Exposure, clamp and cut for bilateral facial nerve trunks were performed in the rats of the injury groups, and no injury was inflicted on the rats of the control group. MAIN OUTCOME MEASURES; The brainstems of all the rats were excised on days 1, 3, 7, and 14 post injury, and then the facial nuclei were stained with hematoxylin-eosin to observe any pathological changes due to apoptosis in facial neurons. PSD-95 expression in facial nuclei was detected by immunohistochemistry and the number of PSD-95 positive cells was counted under a light microscope. RESULTS： The expression of PSD-95 in the facial nucleus and morphology of the facial neuron within the exposure group had no obvious changes at various points in time tested （P 〉 0.05）. However, the expressions of PSD-95 in the facial nucleus of the clamp group and cut group increased on day 1 post injury （P 〈 0.05）, and showed further increase on day 7 post injury （P 〈 0.01 ）. This did not decrease until day 14 post injury. Facial neuron apoptosis was detected on day 3 post injury and this was even more obvious on day 7 and was maintained to day 14 post injury. The number of cells expressing PSD-95 and displaying severe degrees of facial neuron apoptosis were as follows： cut group 〉 clamp group 〉 exposure group. CONCLUSION： The apoptotic extent of facial neurons and the expression of PSD-95 in apoptotic facial neurons increased with the degree of aggravation of injured severity of facial nerve.
基金supported by the National Natural Science Foundation of China (30170220)Xuzhou Science and Technology Bureau of China (XZZD1157)+1 种基金Xuzhou Medical College (2011KJZ03)A Project Funded by the Priority Academic Program Development of Jingsu Higher Education Institutions
文摘Objective Postsynaptic density protein 95 （PSD-95） plays important roles in the regulation of glutamate signaling, such as that of N-methyl-D-aspartate receptors （NMDARs）. In this study, the functional roles of PSD-95 in tyrosine phosphorylafion of NMDAR subunit 2A （NR2A） and in apoptosis-like cell death induced by oxygen-glucose de- privation （OGD） in cultured rat cortical neurons were investigated. Methods We used immunoprecipitation and immuno- blotting to detect PSD-95 protein level, tyrosine phosphorylation level of NR2A, and the interaction between PSD-95 and NR2A or Src. Apoptosis-like cells were observed by 4,6-diamidino-2-phenylindole staining. Results Tyrosine phospho- rylation of NR2A and apoptosis-like cell death were increased after recovery following 60-min OGD. The increases were attenuated by pretreatment with antisense oligonucleotides against PSD-95 before OGD, but not by missense oligonucle- otides or vehicle. PSD-95 antisense oligonucleotides also inhibited the increased interaction between PSD-95 and NR2A or Src, while NR2A expression did not change under this condition. Conclusion PSD-95 may be involved in regulating NR2A tyrosine phosphorylation by Src kinase. Inhibition of PSD-95 expression can be neuroprotective against apoptosis- like cell death after recovery from OGD.
基金the National Natural Science Foundation of China,No.30472214
文摘BACKGROUND： The change in expression of synaptophysin （Syp） and postsynaptic density-95 （PSD-95） alters after cerebral infarction, and the plasticity of synapses contributes greatly to nerve function recovery. Chinese medicinal substances may play an important role in the expression of Syp and PSD-95. OBJECTIVE： To observe the effect of Panaxtriol Saponins （PTS）, an active component in Sanqi tongshu capsules, on the expression of Syp and PSD-95 after cerebral infarction at different time points in rats, so as to examine the cerebral function remodeling mechanism. DESIGN, TIME AND SETTING： A randomized and controlled observation which was performed in Dongzhimen Hospital, Beijing University of Traditional Chinese Medicine from January to March, 2007. MATERIALS： Twenty-six healthy male Sprague Dawley rats were used to establish middle cerebral artery occlusion based on the Longa method. Sanqi tongshu capsules （containing 100 mg PTS per tablet） were provided by the Chengdu Huashen Group and nimodipine tablets （30 mg） by Tianjin Zhongyang Pharmaceutical Co., Ltd. METHODS： Twenty-six rats were randomly divided into an operation group （n = 21 ） and a control group （n = 5）. The operation group underwent the EZ Longa procedure to make the middle cerebral artery occlusion model. After surgery rats were randomly divided into a model group, a PTS group and a nimodipine group, with seven rats in each group. Rats were intragastrically administrated with saline （2 mL/d） in the model group, with Sanqi tongshu capsule （5.4 mg/100 g/d） in the PTS group, and with nimodipine （1.73 mg/100 g/d） in the nimodipine group. Rats in the control group did not undergo model establishment and drug administration. MAIN OUTCOME MEASURES： The expressions of Syp and PSD-95 were measured by immunohistochemical and image analysis at days 3, 7 and 28 after the operation. RESULTS： The expression of Syp and PSD-95 in the operation group was significantly lower than in the control group at days 3, 7, 28 postoperatively （P 〈 0.05）. The expression of Syp and PSD-95 in the PTS group and nimodipine group was significantly higher than in the model group at day 28 postoperatively （P 〈 0.05-0.01）. Additionally, after PTS and nimodipine treatment at different intervals, the expression of Syp and PSD-95 at day 28 postoperatively was significantly higher than those at days 3 and 7 postoperatively, respectively （P 〈 0.01）. CONCLUSION： PTS can promote the expression of Syp and PSD-95, i.e. the remodeling process of synapses, after cerebral infarction at different time points in rats, which contributes to cerebral function remodeling.
基金supported by Postdoc Fellowship from the Foundation for Angelman Syndrome Therapeutics(FT2022-005 to JM,PD2023-001 to XY,and FT2024-001 to YAH)STTR R41 MH118747(to JM)。
文摘Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term potentiation.Postsynaptically,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation.In this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression.Treatment with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform.Although TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions.Targeting TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.
文摘目的:研究三七通舒胶囊有效成分三七三醇皂苷对大鼠脑梗死后不同时点Syp和PSD-95表达的影响,为探讨脑功能重塑的机理提供理论依据。方法:健康雄性SD大鼠,分为手术和正常组,手术组采用改良的Longa方法制备大鼠大脑中动脉阻塞模型,分为模型组、三七三醇皂苷组和尼莫地平组,于术后3 d、7 d和28 d 3个时间点利用免疫组化及图像分析测定大鼠脑内Syp和PSD-95的表达。结果:术后28 d三七三醇皂苷组和尼莫地平组较模型组的Syp表达上升显著(P<0.01),PSD-95表达上升亦显著(P<0.05和P<0.01),且前两者较自身3 d、7 d Syp和PSD-95表达均有显著升高(P<0.01)。结论:三七三醇皂苷可以促进大鼠脑梗死后不同时点Syp和PSD-95表达,即突触的重塑过程,对大脑功能重塑有积极作用。
文摘目的检测脑挫伤修复过程中突触后致密蛋白(postsynaptic density protein 95,PSD-95)的表达,探讨其变化规律与损伤时间的相关性。方法雄性SD大鼠50只,随机分为8个实验组,1个对照组,每组5只。制作大鼠脑挫伤模型,于伤后3、6、12h和3、5、7、10d取脑组织,应用免疫组织化学技术和免疫蛋白印迹(Western blot)方法检测脑挫伤后不同时间脑组织中PSD-95的表达变化。结果对照组脑组织仅有少量PSD-95阳性细胞;实验组中,伤后3h、6h组脑组织出现较多PSD-95阳性细胞,12h组阳性细胞数量持续升高,伤后1d阳性细胞数下降,5d后又升高并达到高峰,7d、10d恢复;计算阳性率,统计分析结果显示,阳性细胞数与相邻上组比较,存在显著性差异。Western blot结果:挫伤后,3～12h表达量上升,1d下降,随后又逐步上升,5d达到高峰,7d、10d下降;应用Fluorchem V2.0 Stand Alone软件获取感光条带的平均灰度值,经统计分析,各组与相邻上组比较,存在显著性差异。结论大鼠脑损伤后损伤周边区PSD-95呈现升高→下降→再升高→再下降的表达规律,对损伤时间推断有一定的参考意义。
文摘目的观察小鼠学习记忆能力及其海马区突触功能相关蛋白脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)、突触后致密蛋白95(postsynaptic density protein 95,PSD95)及GluA1表达的增龄性变化。方法观察10周龄(青年组)和21月龄(老年组)C57BL/6雄性小鼠Morris水迷宫训练和测试表现,并应用Western blot技术检测两组小鼠海马区BDNF、PSD95、GluA1的蛋白表达。结果与青年组相比,老年组小鼠水迷宫测试中的学习记忆能力明显下降(P均<0.05),其海马区总蛋白BDNF、PSD95、GluA1的表达量均显著下降(P均<0.05),海马区膜蛋白GluA1的表达量也明显下降(P<0.05)。结论老年小鼠学习记忆能力下降伴随着海马区突触功能相关蛋白BDNF、PSD95、GluA1表达的一致下降。
文摘目的探讨戊四氮点燃癫痫对大鼠空间学习记忆的影响及可能的分子机制。方法戊四氮(pentylenetet-razol,PTZ)点燃建立慢性癫痫(chronic epileptic,CEP)模型,Morris水迷宫进行行为学检测,免疫组织化学方法观察大鼠海马CA1、CA3区突触素(synaptophysin,P38)和突触后致密物95(postsynaptic density 95,PSD-95)的表达,并用计算机图像分析系统对免疫反应结果进行处理。结果水迷宫试验检测癫痫组大鼠空间学习记忆能力受损;免疫组化结果表明其海马CA1、CA3区P38和PSD-95免疫反应产物较对照组明显减少(P<0.01,P<0.05)。结论戊四氮点燃癫痫大鼠伴有学习记忆功能减退,其海马神经元P38和PSD-95的表达减少可能参与了空间学习记忆受损。
文摘目的:研究温胆汤对精神分裂症模型大鼠行为学及其海马神经元突触后致密蛋白95(PSD-95)、生长相关蛋白43(GAP-43)、JNK相互作用蛋白3(JIP-3)、连接蛋白43(Cx-43)表达的影响。方法:将SD大鼠随机分为:正常对照组、模型对照组、氯氮平0.02 g/kg组、温胆汤10、20、40 g/kg组。正常对照组和模型对照组分别灌胃生理盐水,各组分别灌胃相应药物,1次/d,连续给药21 d。末次给药2 h后,除正常对照组外,其余各组一次性腹腔注射MK-8010.6 mg/kg,以诱发精神分裂症模型。造模后,观察记录各组大鼠的行为学改变和刻板行为评分,旷场实验评价大鼠滞留时间及穿越次数;RT-q PCR法检测大鼠海马组织Psd95、Gap43、Jip3、Cx43 m RNA表达;WB法检测大鼠海马组织PSD-95、GAP-43、JIP-3、Cx-43蛋白表达。结果:与正常对照组比较,模型对照组大鼠刻板行为评分显著升高,在中央区滞留时间及穿越次数显著下降(P<0.01);其海马组织Psd95、Gap43、Jip3、Cx43 m RNA和蛋白表达显著下调(P<0.01);与模型对照组比较,温胆汤10、20、40 g/kg组均能明显降低大鼠刻板行为评分,明显升高中央区滞留时间及穿越频次(P<0.05或P<0.01);能明显上调海马组织Psd95、Gap43、Jip3、Cx43 m RNA和蛋白的表达(P<0.05或P<0.01)。结论:温胆汤可能通过上调PSD-95、GAP-43、JIP-3、Cx-43等突触相关蛋白的表达,从而调控海马神经元突触可塑性,缓解刻板行为和紧张、焦虑等情绪,增强学习和记忆功能,有效改善精神分裂症的认知障碍。
