Pub Date : 2024-06-05Epub Date: 2024-04-26DOI: 10.1097/WNR.0000000000002040
Yulin Li, Xue Sui, Yutong Li
Objective: This study examined the effect of context on the prediction of emotional words with varying valences. It investigated the neural mechanisms underlying the processing differences of emotion words with different valences in both predictable and unpredictable contexts. Additionally, it aimed to address the conflicting results regarding the processing time in predictive contexts reported in previous studies.
Methods: Participants were instructed to carefully read the text that included the specified emotion words. Event-related potentials elicited by emotional words were measured. To ensure that the participants can read the text carefully, 33% of the texts are followed by comprehension problems. After reading the text, the comprehension questions were answered based on the text content.
Results: The study revealed that the N400 amplitude elicited by an unpredictable context was greater than that elicited by a predictable context. Additionally, the N400 amplitude triggered by positive emotion words was larger than that triggered by negative emotion words. However, there was no significant difference in late positive component amplitude observed between contextual prediction and emotional word valence.
Conclusion: The present study suggests that predictive processing takes place at an intermediate stage of speech processing, approximately 400 ms after stimulus onset. Furthermore, the presence of a predictive context enhances the processing of emotional information. Notably, brain activity is more pronounced during the processing of positive emotional stimuli compared to negative emotional stimuli. Additionally, the facilitative effect of a predictable context diminishes in the advanced phase of Chinese speech comprehension.
{"title":"Effect of contextual prediction on emotional word processing: an evidence from ERPNR-D-24-00189.","authors":"Yulin Li, Xue Sui, Yutong Li","doi":"10.1097/WNR.0000000000002040","DOIUrl":"10.1097/WNR.0000000000002040","url":null,"abstract":"<p><strong>Objective: </strong>This study examined the effect of context on the prediction of emotional words with varying valences. It investigated the neural mechanisms underlying the processing differences of emotion words with different valences in both predictable and unpredictable contexts. Additionally, it aimed to address the conflicting results regarding the processing time in predictive contexts reported in previous studies.</p><p><strong>Methods: </strong>Participants were instructed to carefully read the text that included the specified emotion words. Event-related potentials elicited by emotional words were measured. To ensure that the participants can read the text carefully, 33% of the texts are followed by comprehension problems. After reading the text, the comprehension questions were answered based on the text content.</p><p><strong>Results: </strong>The study revealed that the N400 amplitude elicited by an unpredictable context was greater than that elicited by a predictable context. Additionally, the N400 amplitude triggered by positive emotion words was larger than that triggered by negative emotion words. However, there was no significant difference in late positive component amplitude observed between contextual prediction and emotional word valence.</p><p><strong>Conclusion: </strong>The present study suggests that predictive processing takes place at an intermediate stage of speech processing, approximately 400 ms after stimulus onset. Furthermore, the presence of a predictive context enhances the processing of emotional information. Notably, brain activity is more pronounced during the processing of positive emotional stimuli compared to negative emotional stimuli. Additionally, the facilitative effect of a predictable context diminishes in the advanced phase of Chinese speech comprehension.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"584-589"},"PeriodicalIF":1.6,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140869198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neuroinflammation after traumatic brain injury (TBI) exhibits a strong correlation with neurological impairment, which is a crucial target for improving the prognosis of TBI patients. The involvement of CXCL5/CXCR2 signaling in the regulation of neuroinflammation in brain injury models has been documented. Therefore, the effects of CXCL5 on post-TBI neuroinflammation and its potential mechanisms need to be explored. Following TBI, C57BL/6 mice were administered intraperitoneal injections of a CXCL5 neutralizing antibody (Nab-CXCL5) (5 mg/kg, 2 times/day). Subsequently, the effects on neuroinflammation, nerve injury, and neurological function were assessed. Nab-CXCL5 significantly reduced the release of inflammatory factors, inhibited the formation of inflammatory microglia and astrocytes, and reduced the infiltration of peripheral immune cells in TBI mice. Additionally, this intervention led to a reduction in neuronal impairment and facilitated the restoration of sensorimotor abilities, as well as improvements in learning and memory functions. Peripheral administration of the Nab-CXCL5 to TBI mice could suppress neuroinflammation, reduce neurological damage, and improve neurological function. Our data suggest that neutralizing antibodies against CXCL5 (Nab-CXCL5) may be a promising agent for treating TBI.
{"title":"Intervention of CXCL5 attenuated neuroinflammation and promoted neurological recovery after traumatic brain injury.","authors":"Leiyang Li, Jinpeng Zhou, Liying Han, Chengxuan Guo, Shuoyao Ma, Shunnan Ge, Yan Qu","doi":"10.1097/WNR.0000000000002032","DOIUrl":"10.1097/WNR.0000000000002032","url":null,"abstract":"<p><p>Neuroinflammation after traumatic brain injury (TBI) exhibits a strong correlation with neurological impairment, which is a crucial target for improving the prognosis of TBI patients. The involvement of CXCL5/CXCR2 signaling in the regulation of neuroinflammation in brain injury models has been documented. Therefore, the effects of CXCL5 on post-TBI neuroinflammation and its potential mechanisms need to be explored. Following TBI, C57BL/6 mice were administered intraperitoneal injections of a CXCL5 neutralizing antibody (Nab-CXCL5) (5 mg/kg, 2 times/day). Subsequently, the effects on neuroinflammation, nerve injury, and neurological function were assessed. Nab-CXCL5 significantly reduced the release of inflammatory factors, inhibited the formation of inflammatory microglia and astrocytes, and reduced the infiltration of peripheral immune cells in TBI mice. Additionally, this intervention led to a reduction in neuronal impairment and facilitated the restoration of sensorimotor abilities, as well as improvements in learning and memory functions. Peripheral administration of the Nab-CXCL5 to TBI mice could suppress neuroinflammation, reduce neurological damage, and improve neurological function. Our data suggest that neutralizing antibodies against CXCL5 (Nab-CXCL5) may be a promising agent for treating TBI.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":"35 9","pages":"549-557"},"PeriodicalIF":1.6,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-05Epub Date: 2024-04-29DOI: 10.1097/WNR.0000000000002041
Qing-Na Hao, Xiao-Bo Xue, Heng Zhou, Zhao-Li Hu
Pyroptosis, a form of programmed cell death, drives inflammation in the context of cerebral ischemia/reperfusion. The molecular mechanism of pyroptosis underlying ischemia/reperfusion, however, is not fully understood. The transient middle cerebral artery occlusion was applied to wild-type and caspase-1 knockout mice. 2,3,5-Triphenyltetrazolium chloride-staining and immunohistochemistry were used to identify the ischemic region, and western blot and immunofluorescence for the examination of neuronal pyroptosis. The expression of inflammatory factors and the behavioral function assessments were further conducted to examine the effects of caspase-1 knockout on protection against ischemia/reperfusion injury. Ischemia/reperfusion injury increased pyroptosis-related signals represented by the overexpression of pyroptosis-related proteins including caspase-1 and gasdermin D (GSDMD). Meanwhile, the number of GSDMD positive neurons increased in penumbra by immunofluorescence staining. Compared with wild-type mice, those with caspase-1 knockout exhibited decreased levels of pyroptosis-related proteins following ischemia/reperfusion. Furthermore, ischemia/reperfusion attack-induced brain infarction, cerebral edema, inflammatory factors, and neurological outcomes were partially improved in caspase-1 knockout mice. The data indicate that pyroptosis participates in ischemia/reperfusion induced-damage, and the caspase-1 might be involved, it provides some new insights into the molecular mechanism of ischemia.
在脑缺血/再灌注的情况下,嗜热细胞增多症(一种程序性细胞死亡)会引发炎症。然而,缺血/再灌注所引发的裂解热的分子机制尚未完全明了。对野生型小鼠和 caspase-1 基因敲除小鼠进行瞬时大脑中动脉闭塞实验。采用 2,3,5-三苯基氯化四氮唑染色法和免疫组化法确定缺血区域,并用 Western 印迹法和免疫荧光法检测神经元热解。为了研究caspase-1基因敲除对缺血再灌注损伤的保护作用,还进一步进行了炎症因子表达和行为功能评估。缺血/再灌注损伤增加了热蛋白沉积相关信号,表现为包括caspase-1和gasdermin D(GSDMD)在内的热蛋白沉积相关蛋白的过度表达。同时,通过免疫荧光染色,半影中 GSDMD 阳性神经元的数量增加。与野生型小鼠相比,caspase-1基因敲除的小鼠在缺血/再灌注后表现出热休克相关蛋白水平的下降。此外,缺血再灌注诱发的脑梗塞、脑水肿、炎症因子和神经系统结果在caspase-1基因敲除小鼠中得到了部分改善。这些数据表明,热蛋白沉积参与了缺血/再灌注诱导的损伤,而caspase-1可能参与其中,这为缺血的分子机制提供了一些新的见解。
{"title":"Caspase-1 deletion reveals pyroptosis participates in neural damage induced by cerebral ischemia/reperfusion in tMCAO model mice.","authors":"Qing-Na Hao, Xiao-Bo Xue, Heng Zhou, Zhao-Li Hu","doi":"10.1097/WNR.0000000000002041","DOIUrl":"10.1097/WNR.0000000000002041","url":null,"abstract":"<p><p>Pyroptosis, a form of programmed cell death, drives inflammation in the context of cerebral ischemia/reperfusion. The molecular mechanism of pyroptosis underlying ischemia/reperfusion, however, is not fully understood. The transient middle cerebral artery occlusion was applied to wild-type and caspase-1 knockout mice. 2,3,5-Triphenyltetrazolium chloride-staining and immunohistochemistry were used to identify the ischemic region, and western blot and immunofluorescence for the examination of neuronal pyroptosis. The expression of inflammatory factors and the behavioral function assessments were further conducted to examine the effects of caspase-1 knockout on protection against ischemia/reperfusion injury. Ischemia/reperfusion injury increased pyroptosis-related signals represented by the overexpression of pyroptosis-related proteins including caspase-1 and gasdermin D (GSDMD). Meanwhile, the number of GSDMD positive neurons increased in penumbra by immunofluorescence staining. Compared with wild-type mice, those with caspase-1 knockout exhibited decreased levels of pyroptosis-related proteins following ischemia/reperfusion. Furthermore, ischemia/reperfusion attack-induced brain infarction, cerebral edema, inflammatory factors, and neurological outcomes were partially improved in caspase-1 knockout mice. The data indicate that pyroptosis participates in ischemia/reperfusion induced-damage, and the caspase-1 might be involved, it provides some new insights into the molecular mechanism of ischemia.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"577-583"},"PeriodicalIF":1.6,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Modern medicine has unveiled that essential oil made from Aquilaria possesses sedative and hypnotic effects. Among the chemical components in Aquilaria, nerolidol, a natural sesquiterpene alcohol, has shown promising effects. This study aimed to unravel the potential of nerolidol in treating depression. Chronic unpredictable mild stress (CUMS) was utilized to induce depression-like behavior in mice, and open field test, sucrose preference, and tail suspension test was conducted. The impacts of nerolidol on the inflammatory response, microglial activation, and DNA methyltransferase 1 (DNMT1) were assessed. To study the regulatory role of DNMT1, lipopolysaccharide (LPS) was used to treat BV2 cells, followed by the evaluation of cell viability and DNMT1 level. Additionally, the influence of DNMT1 overexpression on BV2 cell activation was determined. Behavioral analysis revealed that nerolidol reduced depression-like behavior in mice. Nerolidol reduced the levels of inflammatory factors and microglial activation caused by CUMS. Nerolidol treatment was found to reduce DNMT1 levels in mouse brain tissue and it also decrease the LPS-induced increase in DNMT1 levels in BV2 cells. DNMT1 overexpression reversed the impacts of nerolidol on the inflammation response and cell activation. This study underscores the potential of nerolidol in reducing CUMS-induced depressive-like behavior and inhibiting microglial activation by downregulating DNMT1. These findings offer valuable insights into the potential of nerolidol as a therapeutic option for depression.
{"title":"Nerolidol reduces depression-like behavior in mice and suppresses microglia activation by down-regulating DNA methyltransferase 1.","authors":"Guangcai Zhang, Xiaohui Zhou, Qifan Feng, Weihua Ke, Jiahui Pan, Haiying Zhang, Yixian Luan, Beibei Lei","doi":"10.1097/WNR.0000000000002029","DOIUrl":"10.1097/WNR.0000000000002029","url":null,"abstract":"<p><p>Modern medicine has unveiled that essential oil made from Aquilaria possesses sedative and hypnotic effects. Among the chemical components in Aquilaria, nerolidol, a natural sesquiterpene alcohol, has shown promising effects. This study aimed to unravel the potential of nerolidol in treating depression. Chronic unpredictable mild stress (CUMS) was utilized to induce depression-like behavior in mice, and open field test, sucrose preference, and tail suspension test was conducted. The impacts of nerolidol on the inflammatory response, microglial activation, and DNA methyltransferase 1 (DNMT1) were assessed. To study the regulatory role of DNMT1, lipopolysaccharide (LPS) was used to treat BV2 cells, followed by the evaluation of cell viability and DNMT1 level. Additionally, the influence of DNMT1 overexpression on BV2 cell activation was determined. Behavioral analysis revealed that nerolidol reduced depression-like behavior in mice. Nerolidol reduced the levels of inflammatory factors and microglial activation caused by CUMS. Nerolidol treatment was found to reduce DNMT1 levels in mouse brain tissue and it also decrease the LPS-induced increase in DNMT1 levels in BV2 cells. DNMT1 overexpression reversed the impacts of nerolidol on the inflammation response and cell activation. This study underscores the potential of nerolidol in reducing CUMS-induced depressive-like behavior and inhibiting microglial activation by downregulating DNMT1. These findings offer valuable insights into the potential of nerolidol as a therapeutic option for depression.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"457-465"},"PeriodicalIF":1.6,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-08Epub Date: 2024-03-15DOI: 10.1097/WNR.0000000000002030
Fengwei Zheng, Weixin Li, Shaobo Su, Qiaoyan Hui
Diffuse axonal injury (DAI) is a critical pathological facet of traumatic brain injury (TBI). Oxidative stress plays a significant role in the progress of DAI. Annexin A1 (AnxA1) has been demonstrated to benefit from recovery of neurofunctional outcomes after TBI. However, whether AnxA1 exhibits neuronal protective function by modulating oxidative stress in DAI remains unknown. Expression of AnxA1 was evaluated via real-time PCR and western blotting in rat brainstem after DAI. The neurological effect of AnxA1 following DAI through quantification of modified neurologic severity score (mNSS) was compared between wild-type and AnxA1-knockout rats. Brain edema and neuronal apoptosis, as well as expression of oxidative factors and inflammatory cytokines, were analyzed between wild-type and AnxA1 deficiency rats after DAI. Furthermore, mNSS, oxidative and inflammatory cytokines were assayed after timely administration of recombinant AnxA1 for DAI rats. In the brainstem of DAI, the expression of AnxA1 remarkably increased. Ablation of AnxA1 increased the mNSS score and brain water content of rats after DAI. Neuron apoptosis in the brainstem after DAI was exaggerated by AnxA1 deficiency. In addition, AnxA1 deficiency significantly upregulated the level of oxidative and inflammatory factors in the brainstem of DAI rats. Moreover, mNSS decreased by AnxA1 treatment in rats following DAI. Expression of oxidative and inflammatory molecules in rat brainstem subjected to DAI inhibited by AnxA1 administration. AnxA1 exhibited neuronal protective function in the progression of DAI mainly dependent on suppressing oxidative stress and inflammation.
弥漫性轴索损伤(DAI)是创伤性脑损伤(TBI)的一个重要病理特征。氧化应激在弥漫性轴索损伤的进展过程中起着重要作用。事实证明,Annexin A1(AnxA1)有利于创伤性脑损伤后神经功能的恢复。然而,AnxA1 是否通过调节 DAI 中的氧化应激而发挥保护神经元的功能仍是未知数。我们通过实时 PCR 和 Western 印迹技术评估了 AnxA1 在 DAI 后大鼠脑干中的表达。通过量化改良神经系统严重程度评分(mNSS),比较了野生型大鼠和 AnxA1 基因敲除大鼠在 DAI 后 AnxA1 对神经系统的影响。分析了野生型大鼠和 AnxA1 基因缺失大鼠在 DAI 后的脑水肿、神经细胞凋亡以及氧化因子和炎症细胞因子的表达情况。此外,在给 DAI 大鼠及时注射重组 AnxA1 后,还检测了 mNSS、氧化因子和炎性细胞因子。在 DAI 大鼠的脑干中,AnxA1 的表达明显增加。消融 AnxA1 增加了 DAI 大鼠的 mNSS 评分和脑水含量。AnxA1 缺乏会加重 DAI 后脑干神经元的凋亡。此外,缺乏 AnxA1 会显著上调 DAI 大鼠脑干中氧化和炎症因子的水平。此外,大鼠脑干损伤后,经 AnxA1 处理,mNSS 水平下降。给予 AnxA1 可抑制 DAI 大鼠脑干中氧化和炎症分子的表达。AnxA1在DAI进展过程中对神经元的保护功能主要依赖于抑制氧化应激和炎症。
{"title":"Annexin A1 conveys neuroprotective function via inhibiting oxidative stress in diffuse axonal injury of rats.","authors":"Fengwei Zheng, Weixin Li, Shaobo Su, Qiaoyan Hui","doi":"10.1097/WNR.0000000000002030","DOIUrl":"10.1097/WNR.0000000000002030","url":null,"abstract":"<p><p>Diffuse axonal injury (DAI) is a critical pathological facet of traumatic brain injury (TBI). Oxidative stress plays a significant role in the progress of DAI. Annexin A1 (AnxA1) has been demonstrated to benefit from recovery of neurofunctional outcomes after TBI. However, whether AnxA1 exhibits neuronal protective function by modulating oxidative stress in DAI remains unknown. Expression of AnxA1 was evaluated via real-time PCR and western blotting in rat brainstem after DAI. The neurological effect of AnxA1 following DAI through quantification of modified neurologic severity score (mNSS) was compared between wild-type and AnxA1-knockout rats. Brain edema and neuronal apoptosis, as well as expression of oxidative factors and inflammatory cytokines, were analyzed between wild-type and AnxA1 deficiency rats after DAI. Furthermore, mNSS, oxidative and inflammatory cytokines were assayed after timely administration of recombinant AnxA1 for DAI rats. In the brainstem of DAI, the expression of AnxA1 remarkably increased. Ablation of AnxA1 increased the mNSS score and brain water content of rats after DAI. Neuron apoptosis in the brainstem after DAI was exaggerated by AnxA1 deficiency. In addition, AnxA1 deficiency significantly upregulated the level of oxidative and inflammatory factors in the brainstem of DAI rats. Moreover, mNSS decreased by AnxA1 treatment in rats following DAI. Expression of oxidative and inflammatory molecules in rat brainstem subjected to DAI inhibited by AnxA1 administration. AnxA1 exhibited neuronal protective function in the progression of DAI mainly dependent on suppressing oxidative stress and inflammation.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"466-475"},"PeriodicalIF":1.6,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-08Epub Date: 2024-03-14DOI: 10.1097/WNR.0000000000002033
Yanyan Huang, Meijun Liu, Zhiyao Zheng, Ruiping Lu, Chunlu Li, Min Su, Yixin Li, Baijuan Xia
This study aimed to investigate the effects of SIRT1 modulation on heroin addiction-like behavior and its possible biological mechanisms. Wild-type C57BL/6J and Sirt1loxp/loxp D1-Cre mice were used in this experiment, and Sirt1 loxp/loxp D1-Cre(-) mice were used as a control for conditional knockout mice. Mice were divided into saline control and heroin-dependent groups. Behavioral methods were used to record the withdrawal response, conditioned place preference (CPP) changes, and open field test results. Transmission electron microscopy (TEM) was used to observe the structure of autophagosomes in nucleus accumbens (NAc) neurons. The expression of SIRT1 and autophagy-related proteins and genes, such as LC3Ⅱ, ATG5 , and ATG7 , was detected in the NAc of each mouse group via western blot, real-time quantitative PCR (qPCR) analyzes, and immunofluorescence. The results of this experiment showed that compared with the saline group, mice in the wild-type heroin-dependent group showed marked withdrawal symptoms, with more autophagosomes observed in NAc via TEM. Compared with wild-type and Sirt1loxp/loxp D1-Cre(-) heroin-dependent groups, CPP formation was found to be reduced in the conditional knockout mouse group, with a significant decrease in spontaneous activity. Western blot, qPCR, and immunofluorescence results indicated that the expression of LC3Ⅱ, ATG-5, and ATG-7 was significantly reduced in the NAc of the Sirt1loxp/loxp D1-Cre(+) group. It was still, however, higher than that in the saline control group. These results suggest that inhibition of Sirt1 expression may prevent heroin-induced addiction-related behaviors via reducing D1 neuronal autophagy.
{"title":"Inhibition of SIRT1 in the nucleus accumbens attenuates heroin addiction-related behavior by decreasing D1 neuronal autophagy.","authors":"Yanyan Huang, Meijun Liu, Zhiyao Zheng, Ruiping Lu, Chunlu Li, Min Su, Yixin Li, Baijuan Xia","doi":"10.1097/WNR.0000000000002033","DOIUrl":"10.1097/WNR.0000000000002033","url":null,"abstract":"<p><p>This study aimed to investigate the effects of SIRT1 modulation on heroin addiction-like behavior and its possible biological mechanisms. Wild-type C57BL/6J and Sirt1loxp/loxp D1-Cre mice were used in this experiment, and Sirt1 loxp/loxp D1-Cre(-) mice were used as a control for conditional knockout mice. Mice were divided into saline control and heroin-dependent groups. Behavioral methods were used to record the withdrawal response, conditioned place preference (CPP) changes, and open field test results. Transmission electron microscopy (TEM) was used to observe the structure of autophagosomes in nucleus accumbens (NAc) neurons. The expression of SIRT1 and autophagy-related proteins and genes, such as LC3Ⅱ, ATG5 , and ATG7 , was detected in the NAc of each mouse group via western blot, real-time quantitative PCR (qPCR) analyzes, and immunofluorescence. The results of this experiment showed that compared with the saline group, mice in the wild-type heroin-dependent group showed marked withdrawal symptoms, with more autophagosomes observed in NAc via TEM. Compared with wild-type and Sirt1loxp/loxp D1-Cre(-) heroin-dependent groups, CPP formation was found to be reduced in the conditional knockout mouse group, with a significant decrease in spontaneous activity. Western blot, qPCR, and immunofluorescence results indicated that the expression of LC3Ⅱ, ATG-5, and ATG-7 was significantly reduced in the NAc of the Sirt1loxp/loxp D1-Cre(+) group. It was still, however, higher than that in the saline control group. These results suggest that inhibition of Sirt1 expression may prevent heroin-induced addiction-related behaviors via reducing D1 neuronal autophagy.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"486-498"},"PeriodicalIF":1.6,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-08Epub Date: 2024-03-12DOI: 10.1097/WNR.0000000000002028
Peifang Li, Honglin Lu, Xiaoman Shi, Jiajia Yan, Lixia Zhou, Jipeng Yang, Binbin Wang, Yanying Zhao, Luji Liu, Yipu Zhu, Lei Xu, Xiaoli Yang, Xudong Su, Yi Yang, Tong Zhang, Li Guo, Xiaoyun Liu
This study aimed to assess the effects of human urinary kallidinogenase (HUK) on motor function outcome and corticospinal tract recovery in patients with acute ischemic stroke (AIS). This study was a randomized, controlled, single-blinded trial. Eighty AIS patients were split into two groups: the HUK and control groups. The HUK group was administered HUK and standard treatment, while the control group received standard treatment only. At admission and discharge, the National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI) and muscle strength were scored. The primary endpoint was the short-term outcomes of AIS patients under different treatments. The secondary endpoint was the degree of corticospinal tract fiber damage under different treatments. There was a significant improvement in the NIHSS Scale, BI and muscle strength scores in the HUK group compared with controls (Mann-Whitney U test; P < 0.05). Diffusion tensor tractography classification and intracranial arterial stenosis were independent predictors of short-term recovery by linear regression analysis. The changes in fractional anisotropy (FA) and apparent diffusion coefficient (ADC) decline rate were significantly smaller in the HUK group than in the control group ( P < 0.05). Vascular endothelial growth factor (VEGF) increased significantly after HUK treatment ( P < 0.05), and the VEGF change was negatively correlated with changes in ADC. HUK is beneficial for the outcome in AIS patients especially in motor function recovery. It may have protective effects on the corticospinal tract which is reflected by the reduction in the FA and ADC decline rates and increased VEGF expression. The study was registered on ClinicalTrials.gov (unique identifier: NCT04102956).
本研究旨在评估人尿凯利苷原酶(HUK)对急性缺血性脑卒中(AIS)患者运动功能预后和皮质脊髓束恢复的影响。该研究是一项随机对照单盲试验。80 名 AIS 患者被分为两组:HUK 组和对照组。HUK 组接受 HUK 和标准治疗,而对照组只接受标准治疗。入院和出院时,对美国国立卫生研究院卒中量表(NIHSS)、巴特尔指数(BI)和肌肉力量进行评分。主要终点是AIS患者在不同治疗方法下的短期疗效。次要终点是不同治疗方法对皮质脊髓束纤维的损伤程度。与对照组相比,HUK 组的 NIHSS 量表、BI 和肌力评分均有明显改善(Mann-Whitney U 检验;P<0.05)。
{"title":"Protective effects of human urinary kallidinogenase against corticospinal tract damage in acute ischemic stroke patients.","authors":"Peifang Li, Honglin Lu, Xiaoman Shi, Jiajia Yan, Lixia Zhou, Jipeng Yang, Binbin Wang, Yanying Zhao, Luji Liu, Yipu Zhu, Lei Xu, Xiaoli Yang, Xudong Su, Yi Yang, Tong Zhang, Li Guo, Xiaoyun Liu","doi":"10.1097/WNR.0000000000002028","DOIUrl":"10.1097/WNR.0000000000002028","url":null,"abstract":"<p><p>This study aimed to assess the effects of human urinary kallidinogenase (HUK) on motor function outcome and corticospinal tract recovery in patients with acute ischemic stroke (AIS). This study was a randomized, controlled, single-blinded trial. Eighty AIS patients were split into two groups: the HUK and control groups. The HUK group was administered HUK and standard treatment, while the control group received standard treatment only. At admission and discharge, the National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI) and muscle strength were scored. The primary endpoint was the short-term outcomes of AIS patients under different treatments. The secondary endpoint was the degree of corticospinal tract fiber damage under different treatments. There was a significant improvement in the NIHSS Scale, BI and muscle strength scores in the HUK group compared with controls (Mann-Whitney U test; P < 0.05). Diffusion tensor tractography classification and intracranial arterial stenosis were independent predictors of short-term recovery by linear regression analysis. The changes in fractional anisotropy (FA) and apparent diffusion coefficient (ADC) decline rate were significantly smaller in the HUK group than in the control group ( P < 0.05). Vascular endothelial growth factor (VEGF) increased significantly after HUK treatment ( P < 0.05), and the VEGF change was negatively correlated with changes in ADC. HUK is beneficial for the outcome in AIS patients especially in motor function recovery. It may have protective effects on the corticospinal tract which is reflected by the reduction in the FA and ADC decline rates and increased VEGF expression. The study was registered on ClinicalTrials.gov (unique identifier: NCT04102956).</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"431-438"},"PeriodicalIF":1.6,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-12DOI: 10.1097/wnr.0000000000002037
Gavin T Kress, Emily S Popa, David A Merrill, Jennifer E Bramen, Prabha Siddarth
Physical activity (PA) is a promising therapeutic for Alzheimer's disease (AD). Only a handful of meta-analyses have studied the impact of PA interventions on regional brain volumes, and none to date has solely included studies on effect of PA on regional brain volumes in individuals with cognitive impairment (CI). In this meta-analysis, we examined whether there is support for the hypothesis that PA interventions positively impact hippocampal volume (HV) in individuals with CI. We also assessed whether the level of CI [mild CI (MCI) vs. AD] impacted this relationship. We identified six controlled trials that met inclusion criteria. These included 236 participants with AD, MCI, or preclinical AD. Data were extracted and analyzed following Cochrane guidelines. We used a random-effects model to estimate the mean change in HV pre- and post-exercise intervention. Forest plots, Hedges' g funnel plots, and Egger's test were used to assess unbiasedness and visualize intervention effects, and Tau2, Cochran's Q, and I2 were calculated to assess heterogeneity. The primary analysis revealed a significant positive effect of PA on total HV. However, sub-group analyses indicated a significant preservation of HV only in individuals with MCI, but not in those with AD. Egger's test indicated no evidence of publication bias. Subgroup analyses also revealed significant heterogeneity only within the MCI cohort for the total and left HV. PA demonstrated a moderate, significant effect in preserving HV among individuals with MCI, but not AD, highlighting a therapeutic benefit, particularly in earlier disease stages.
体力活动(PA)是一种治疗阿尔茨海默病(AD)的有效方法。只有少数荟萃分析研究了体育锻炼干预对区域脑容量的影响,迄今为止还没有一项荟萃分析只研究了体育锻炼对认知障碍(CI)患者区域脑容量的影响。在这项荟萃分析中,我们研究了 PA 干预对 CI 患者海马体积(HV)产生积极影响的假设是否得到支持。我们还评估了 CI 的程度 [轻度 CI (MCI) vs. AD] 是否会影响这种关系。我们确定了六项符合纳入标准的对照试验。其中包括 236 名患有注意力缺失症、MCI 或临床前注意力缺失症的参与者。我们按照 Cochrane 指南对数据进行了提取和分析。我们使用随机效应模型来估算运动干预前后 HV 的平均变化。森林图、Hedges'g 漏斗图和 Egger's 检验用于评估无偏性和可视化干预效果,Tau2、Cochran's Q 和 I2 用于评估异质性。主要分析显示,PA 对总 HV 有明显的积极影响。然而,亚组分析表明,只有 MCI 患者的 HV 有明显的保护作用,而 AD 患者则没有。Egger检验表明没有证据表明存在发表偏倚。亚组分析还显示,只有在MCI队列中,总HV和左侧HV存在显著异质性。PA在保护MCI患者的HV方面具有中等程度的显着效果,但在AD患者中却不明显,这凸显了其治疗效果,尤其是在疾病的早期阶段。
{"title":"The impact of physical exercise on hippocampal atrophy in mild cognitive impairment and Alzheimer's disease: a meta-analysis.","authors":"Gavin T Kress, Emily S Popa, David A Merrill, Jennifer E Bramen, Prabha Siddarth","doi":"10.1097/wnr.0000000000002037","DOIUrl":"https://doi.org/10.1097/wnr.0000000000002037","url":null,"abstract":"Physical activity (PA) is a promising therapeutic for Alzheimer's disease (AD). Only a handful of meta-analyses have studied the impact of PA interventions on regional brain volumes, and none to date has solely included studies on effect of PA on regional brain volumes in individuals with cognitive impairment (CI). In this meta-analysis, we examined whether there is support for the hypothesis that PA interventions positively impact hippocampal volume (HV) in individuals with CI. We also assessed whether the level of CI [mild CI (MCI) vs. AD] impacted this relationship. We identified six controlled trials that met inclusion criteria. These included 236 participants with AD, MCI, or preclinical AD. Data were extracted and analyzed following Cochrane guidelines. We used a random-effects model to estimate the mean change in HV pre- and post-exercise intervention. Forest plots, Hedges' g funnel plots, and Egger's test were used to assess unbiasedness and visualize intervention effects, and Tau2, Cochran's Q, and I2 were calculated to assess heterogeneity. The primary analysis revealed a significant positive effect of PA on total HV. However, sub-group analyses indicated a significant preservation of HV only in individuals with MCI, but not in those with AD. Egger's test indicated no evidence of publication bias. Subgroup analyses also revealed significant heterogeneity only within the MCI cohort for the total and left HV. PA demonstrated a moderate, significant effect in preserving HV among individuals with MCI, but not AD, highlighting a therapeutic benefit, particularly in earlier disease stages.","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":"243 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-10DOI: 10.1097/wnr.0000000000002024
Wenyan Zhong, Jingjing Chen, Yumin He, Li Xiao, Chengfu Yuan
The decline of aging brain neurons is the main cause of various neurodegenerative disease. This study aimed to examine the impact of Balanophora polyandra polysaccharides (BPP) against aging related neuronal deterioration. C57BL/6 mice were fed with regular feed for 27 months to establish a natural aging mouse model. From 3 months of age, mice in the drug-treated group were respectively fed with feed containing 0.05 or 0.18% BPP until 27 months of age. The effects of BPP treatment on the pathological changes of neurons in mice brain were evaluated, as well as autophagy-related and signaling pathway proteins. BPP treatment had a notable positive impact on the pathological injury of cortical and hippocampal neurons, alleviated neuronal degeneration, and enhanced the staining of Nissl bodies in natural aging mice. Furthermore, BPP upregulated autophagy-related proteins LC3 II/I, Parkin, and PINK1 in the cortex and hippocampus of aging mice, and significantly decreased the expression of p62, PI3K, p-protein Kinase B (AKT), and p-mTOR. Immunofluorescence results showed a reduction in the brightness of LC3, which mainly coexpressed with NeuN in natural aging mice brain, and increased LC3-positive neurons were observed after BPP treatment. Collectively, BPP treatment enhanced neuronal autophagy to improve brain functional degradation through the PI3K/AKT/mTOR signaling in natural aging mice. These finding suggested that BPP has potential to mitigate or delay the neurodegeneration associated with aging and further investigation was needed to validate its efficacy in elderly populations.
{"title":"The polysaccharides from Balanophora polyandra enhanced neuronal autophagy to ameliorate brain function decline in natural aging mice through the PI3K/AKT/mTOR signaling pathway.","authors":"Wenyan Zhong, Jingjing Chen, Yumin He, Li Xiao, Chengfu Yuan","doi":"10.1097/wnr.0000000000002024","DOIUrl":"https://doi.org/10.1097/wnr.0000000000002024","url":null,"abstract":"The decline of aging brain neurons is the main cause of various neurodegenerative disease. This study aimed to examine the impact of Balanophora polyandra polysaccharides (BPP) against aging related neuronal deterioration. C57BL/6 mice were fed with regular feed for 27 months to establish a natural aging mouse model. From 3 months of age, mice in the drug-treated group were respectively fed with feed containing 0.05 or 0.18% BPP until 27 months of age. The effects of BPP treatment on the pathological changes of neurons in mice brain were evaluated, as well as autophagy-related and signaling pathway proteins. BPP treatment had a notable positive impact on the pathological injury of cortical and hippocampal neurons, alleviated neuronal degeneration, and enhanced the staining of Nissl bodies in natural aging mice. Furthermore, BPP upregulated autophagy-related proteins LC3 II/I, Parkin, and PINK1 in the cortex and hippocampus of aging mice, and significantly decreased the expression of p62, PI3K, p-protein Kinase B (AKT), and p-mTOR. Immunofluorescence results showed a reduction in the brightness of LC3, which mainly coexpressed with NeuN in natural aging mice brain, and increased LC3-positive neurons were observed after BPP treatment. Collectively, BPP treatment enhanced neuronal autophagy to improve brain functional degradation through the PI3K/AKT/mTOR signaling in natural aging mice. These finding suggested that BPP has potential to mitigate or delay the neurodegeneration associated with aging and further investigation was needed to validate its efficacy in elderly populations.","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":"243 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Our design aimed to explore the potential involvement of matrix metalloproteinase-9 (MMP-9) in the inflammatory response associated with acute ischemic stroke (AIS). We also aimed to preliminarily examine the potential impact of a disintegrin-like and metalloprotease with thrombospondin type I repeats-13 (ADAMTS13) on MMP-9 in AIS. We conducted oxygen-glucose deprivation models of microglia cells and mice models of AIS with middle cerebral artery occlusion (MCAO). We assessed the expression pattern of MMP-9 with western blotting (WB) and real-time quantitative PCR both in vivo and in vitro. MMP-9 downregulation was achieved by using ACE inhibitors such as trandolapril. For the MCAO model, we used ADAMTS13-deficient mice. We then evaluated the related neurological function scores, cerebral edema and infarct volume. The levels of inflammation-related proteins, such as COX2 and iNOS, were assessed using WB, and the expression of inflammatory cytokines was measured via enzyme-linked immuno sorbent assay in vivo. Our findings indicated that MMP-9 was up-regulated while ADAMTS13 was down-regulated in the MCAO model. Knockdown of MMP-9 reduced both inflammation and ischemic brain injury. ADAMTS13 prevented brain damage, improved neurological function and decreased the inflammation response in mice AIS models. Additionally, ADAMTS13 alleviated MMP-9-induced neuroinflammation in vivo. It showed that ADAMTS13 deficiency exacerbated ischemic brain injury through an MMP-9-dependent inflammatory mechanism. Therefore, the ADAMTS13-MMP-9 axis could have therapeutic potential for the treatment of AIS.
{"title":"ADAMTS13 deficiency exacerbates neuroinflammation by targeting matrix metalloproteinase-9 in ischemic brain injury.","authors":"Hongxiang Jiang, Juntao Hu, Peidong He, Yu Wu, Fei Li, Qianxue Chen","doi":"10.1097/wnr.0000000000002017","DOIUrl":"https://doi.org/10.1097/wnr.0000000000002017","url":null,"abstract":"Our design aimed to explore the potential involvement of matrix metalloproteinase-9 (MMP-9) in the inflammatory response associated with acute ischemic stroke (AIS). We also aimed to preliminarily examine the potential impact of a disintegrin-like and metalloprotease with thrombospondin type I repeats-13 (ADAMTS13) on MMP-9 in AIS. We conducted oxygen-glucose deprivation models of microglia cells and mice models of AIS with middle cerebral artery occlusion (MCAO). We assessed the expression pattern of MMP-9 with western blotting (WB) and real-time quantitative PCR both in vivo and in vitro. MMP-9 downregulation was achieved by using ACE inhibitors such as trandolapril. For the MCAO model, we used ADAMTS13-deficient mice. We then evaluated the related neurological function scores, cerebral edema and infarct volume. The levels of inflammation-related proteins, such as COX2 and iNOS, were assessed using WB, and the expression of inflammatory cytokines was measured via enzyme-linked immuno sorbent assay in vivo. Our findings indicated that MMP-9 was up-regulated while ADAMTS13 was down-regulated in the MCAO model. Knockdown of MMP-9 reduced both inflammation and ischemic brain injury. ADAMTS13 prevented brain damage, improved neurological function and decreased the inflammation response in mice AIS models. Additionally, ADAMTS13 alleviated MMP-9-induced neuroinflammation in vivo. It showed that ADAMTS13 deficiency exacerbated ischemic brain injury through an MMP-9-dependent inflammatory mechanism. Therefore, the ADAMTS13-MMP-9 axis could have therapeutic potential for the treatment of AIS.","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":"70 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}