Pub Date : 2024-06-07eCollection Date: 2024-01-01DOI: 10.1515/tnsci-2022-0342
Eric M Rouiller
Motor commands are transmitted from the motor cortical areas to effectors mostly via the corticospinal (CS) projection. Several subcortical motor nuclei also play an important role in motor control, the subthalamic nucleus, the red nucleus, the reticular nucleus and the superior colliculus. These nuclei are influenced by motor cortical areas via respective corticofugal projections, which undergo complex adaptations after motor trauma (spinal cord/motor cortex injury) or motor disease (Parkinson), both in the absence or presence of putative treatments, as observed in adult macaque monkeys. A dominant effect was a nearly complete suppression of the corticorubral projection density and a strong downregulation of the corticoreticular projection density, with the noticeable exception in the latter case of a considerable increase of projection density following spinal cord injury, even enhanced when an anti-NogoA antibody treatment was administered. The effects were diverse and less prominent on the corticotectal and corticosubthalamic projections. The CS projection may still be the major efferent pathway through which motor adaptations can take place after motor trauma or disease. However, the parallel supraspinal motor corticofugal projections may also participate in connectional adaptations supporting the functional recovery of motor abilities, representing potential targets for future clinical strategies, such as selective electrical neurostimulations.
{"title":"Adaptation of the layer V supraspinal motor corticofugal projections from the primary (M1) and premotor (PM) cortices after CNS motor disorders in non-human primates: A survey.","authors":"Eric M Rouiller","doi":"10.1515/tnsci-2022-0342","DOIUrl":"10.1515/tnsci-2022-0342","url":null,"abstract":"<p><p>Motor commands are transmitted from the motor cortical areas to effectors mostly via the corticospinal (CS) projection. Several subcortical motor nuclei also play an important role in motor control, the subthalamic nucleus, the red nucleus, the reticular nucleus and the superior colliculus. These nuclei are influenced by motor cortical areas via respective corticofugal projections, which undergo complex adaptations after motor trauma (spinal cord/motor cortex injury) or motor disease (Parkinson), both in the absence or presence of putative treatments, as observed in adult macaque monkeys. A dominant effect was a nearly complete suppression of the corticorubral projection density and a strong downregulation of the corticoreticular projection density, with the noticeable exception in the latter case of a considerable increase of projection density following spinal cord injury, even enhanced when an anti-NogoA antibody treatment was administered. The effects were diverse and less prominent on the corticotectal and corticosubthalamic projections. The CS projection may still be the major efferent pathway through which motor adaptations can take place after motor trauma or disease. However, the parallel supraspinal motor corticofugal projections may also participate in connectional adaptations supporting the functional recovery of motor abilities, representing potential targets for future clinical strategies, such as selective electrical neurostimulations.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220342"},"PeriodicalIF":2.1,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11163158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31eCollection Date: 2024-01-01DOI: 10.1515/tnsci-2022-0808
Zhengyu Li, Li Gan, Si Yan, Yufang Yan, Wei Huang
[This retracts the article DOI: 10.1515/tnsci-2020-0101.].
[此文撤稿,DOI: 10.1515/tnsci-2020-0101.]。
{"title":"Retraction of \"Effect of C-phycocyanin on HDAC3 and miRNA-335 in Alzheimer's disease\".","authors":"Zhengyu Li, Li Gan, Si Yan, Yufang Yan, Wei Huang","doi":"10.1515/tnsci-2022-0808","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0808","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.1515/tnsci-2020-0101.].</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220808"},"PeriodicalIF":2.1,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-08eCollection Date: 2024-01-01DOI: 10.1515/tnsci-2022-0341
Xiaofang Zhang, Jiyuan Guo, Ce Zhang, Wenhua Wang, Shuailin Du, Xusheng Tian
Calmodulin-dependent protein kinases (CaMKs) are widely regarded as "memory molecules" due to their role in controlling numerous neuronal functions in the brain, and the CaMK signaling pathway plays a crucial role in controlling synaptic plasticity. Suanzaoren decoction (SZRD) can improve depression-like behavior and thus has potential benefits in the clinical treatment of depression; however, its mechanism of action is not fully understood. In this study, we found that key proteins in the CaMK signaling pathway were regulated by the decoction used to treat depression. The purpose of this research was to ascertain if the SZRD's therapeutic efficacy in the treatment of depression is associated with the modulation of key proteins in the CaMK signaling pathway. A rat model of depression was created by exposing the animals to chronic, unexpected, mild stress. Model rats were given intragastric administration of SZRD or fluoxetine every morning once a day. Protein and mRNA relative expression levels of CaM, CaMK I, and CaMK IV in the hippocampus were measured by Western blot, quantitative polymerase chain reaction, and immunohistochemistry in the hippocampus. Our findings demonstrated that SZRD significantly improved the mood of depressed rats. This indicates that SZRD, by modulating the CaMK signaling system, may alleviate depressive symptoms and lessen work and life-related pressures.
{"title":"Suanzaoren decoction exerts its antidepressant effect via the CaMK signaling pathway.","authors":"Xiaofang Zhang, Jiyuan Guo, Ce Zhang, Wenhua Wang, Shuailin Du, Xusheng Tian","doi":"10.1515/tnsci-2022-0341","DOIUrl":"10.1515/tnsci-2022-0341","url":null,"abstract":"<p><p>Calmodulin-dependent protein kinases (CaMKs) are widely regarded as \"memory molecules\" due to their role in controlling numerous neuronal functions in the brain, and the CaMK signaling pathway plays a crucial role in controlling synaptic plasticity. Suanzaoren decoction (SZRD) can improve depression-like behavior and thus has potential benefits in the clinical treatment of depression; however, its mechanism of action is not fully understood. In this study, we found that key proteins in the CaMK signaling pathway were regulated by the decoction used to treat depression. The purpose of this research was to ascertain if the SZRD's therapeutic efficacy in the treatment of depression is associated with the modulation of key proteins in the CaMK signaling pathway. A rat model of depression was created by exposing the animals to chronic, unexpected, mild stress. Model rats were given intragastric administration of SZRD or fluoxetine every morning once a day. Protein and mRNA relative expression levels of CaM, CaMK I, and CaMK IV in the hippocampus were measured by Western blot, quantitative polymerase chain reaction, and immunohistochemistry in the hippocampus. Our findings demonstrated that SZRD significantly improved the mood of depressed rats. This indicates that SZRD, by modulating the CaMK signaling system, may alleviate depressive symptoms and lessen work and life-related pressures.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220341"},"PeriodicalIF":2.1,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03eCollection Date: 2024-01-01DOI: 10.1515/tnsci-2022-0340
Song Luo, Xiao-Rui Wang, Li-Juan Yang, Liang-Yu Zou
Objectives: The FT4-to-FT3 ratio (FFR) variations in patients with subacute combined spinal cord degeneration (SCSD) as a potentially useful prognostic indicator are still unknown. This study aimed to investigate the changes of FFR as a potentially valuable prognostic predictor in patients with SCSD.
Methods: This study included 144 consecutive SCSD patients who received standard diagnostic and therapeutic procedures between January 2015 and December 2021 and were admitted to the Department of Neurology at the First Affiliated Hospital of Bengbu Medical University. At the time of admission, we gathered data on all patients' demographics, daily routines, previous chronic conditions, medication histories, and other clinical details. For the purpose of measuring FFR, blood samples were specifically taken within 48 h of admission. The degree of neurological impairment of patients was assessed using the functional disability scale at the time of admission. At 6 months following discharge, the Modified Rankin Scale (mRS) was used to evaluate the clinical prognosis. To evaluate the relationship between the FFR and the risks of a poor outcome (mRS > 2), univariate and multivariate logistic regression analysis was utilized. The significance of the FT4/FT3 ratio in predicting the clinical outcomes in SCSD patients 6 months after discharge was assessed using the area under curve-receiver operating characteristic (AUC-ROC).
Results: About 90 patients (62.5%) of the 144 patients had poor outcomes, while 54 (37.5%) had favorable outcomes. Higher FFR at admission was independently linked to higher odds of a poor outcome, according to a logistic analysis. With an optimized cutoff value of >2.843, the FFR exhibited the maximum accuracy for predicting a poor outcome, according to the AUC‒ROC curve (AUC 0.731, P < 0.001; sensitivity, 77.8%; specificity, 83.3%). FFR was identified as an independent predictor of poor outcomes by multivariate logistic regression (OR, 2.244; 95% CI, 1.74-2.90; P < 0.001).
Conclusions: We discovered that in patients who had a bad result 6 months after discharge, the FFR had dramatically increased at the time of admission, providing a unique prognostic marker in patients with SCSD.
{"title":"FT4-to-FT3 ratio is a novel prognostic marker in subacute combined spinal cord degeneration patients.","authors":"Song Luo, Xiao-Rui Wang, Li-Juan Yang, Liang-Yu Zou","doi":"10.1515/tnsci-2022-0340","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0340","url":null,"abstract":"<p><strong>Objectives: </strong>The FT4-to-FT3 ratio (FFR) variations in patients with subacute combined spinal cord degeneration (SCSD) as a potentially useful prognostic indicator are still unknown. This study aimed to investigate the changes of FFR as a potentially valuable prognostic predictor in patients with SCSD.</p><p><strong>Methods: </strong>This study included 144 consecutive SCSD patients who received standard diagnostic and therapeutic procedures between January 2015 and December 2021 and were admitted to the Department of Neurology at the First Affiliated Hospital of Bengbu Medical University. At the time of admission, we gathered data on all patients' demographics, daily routines, previous chronic conditions, medication histories, and other clinical details. For the purpose of measuring FFR, blood samples were specifically taken within 48 h of admission. The degree of neurological impairment of patients was assessed using the functional disability scale at the time of admission. At 6 months following discharge, the Modified Rankin Scale (mRS) was used to evaluate the clinical prognosis. To evaluate the relationship between the FFR and the risks of a poor outcome (mRS > 2), univariate and multivariate logistic regression analysis was utilized. The significance of the FT4/FT3 ratio in predicting the clinical outcomes in SCSD patients 6 months after discharge was assessed using the area under curve-receiver operating characteristic (AUC-ROC).</p><p><strong>Results: </strong>About 90 patients (62.5%) of the 144 patients had poor outcomes, while 54 (37.5%) had favorable outcomes. Higher FFR at admission was independently linked to higher odds of a poor outcome, according to a logistic analysis. With an optimized cutoff value of >2.843, the FFR exhibited the maximum accuracy for predicting a poor outcome, according to the AUC‒ROC curve (AUC 0.731, <i>P</i> < 0.001; sensitivity, 77.8%; specificity, 83.3%). FFR was identified as an independent predictor of poor outcomes by multivariate logistic regression (OR, 2.244; 95% CI, 1.74-2.90; <i>P</i> < 0.001).</p><p><strong>Conclusions: </strong>We discovered that in patients who had a bad result 6 months after discharge, the FFR had dramatically increased at the time of admission, providing a unique prognostic marker in patients with SCSD.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220340"},"PeriodicalIF":2.1,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11069125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140869996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-02eCollection Date: 2024-01-01DOI: 10.1515/tnsci-2022-0336
Dione Y L Quek, Natasha Taylor, Moran Gilat, Simon J G Lewis, Kaylena A Ehgoetz Martens
Background: Freezing of gait (FOG) in Parkinson's disease (PD) has a poorly understood pathophysiology, which hinders treatment development. Recent work showed a dysfunctional fronto-striato-limbic circuitry at rest in PD freezers compared to non-freezers in the dopamine "OFF" state. While other studies found that dopaminergic replacement therapy alters functional brain organization in PD, the specific effect of dopamine medication on fronto-striato-limbic functional connectivity in freezers remains unclear.
Objective: To evaluate how dopamine therapy alters resting state functional connectivity (rsFC) of the fronto-striato-limbic circuitry in PD freezers, and whether the degree of connectivity change is related to freezing severity and anxiety.
Methods: Twenty-three PD FOG patients underwent MRI at rest (rsfMRI) in their clinically defined "OFF" and "ON" dopaminergic medication states. A seed-to-seed based analysis was performed between a priori defined limbic circuitry ROIs. Functional connectivity was compared between OFF and ON states. A secondary correlation analyses evaluated the relationship between Hospital Anxiety and Depression Scale (HADS)-Anxiety) and FOG Questionnaire with changes in rsFC from OFF to ON.
Results: PD freezers' OFF compared to ON showed increased functional coupling between the right hippocampus and right caudate nucleus, and between the left putamen and left posterior parietal cortex (PPC). A negative association was found between HADS-Anxiety and the rsFC change from OFF to ON between the left amygdala and left prefrontal cortex, and left putamen and left PPC.
Conclusion: These findings suggest that dopaminergic medication partially modulates the frontoparietal-limbic-striatal circuitry in PD freezers, and that the influence of medication on the amygdala, may be related to clinical anxiety in freezer.
背景:帕金森病(PD)步态冻结(FOG)的病理生理学尚不清楚,这阻碍了治疗方法的开发。最近的研究表明,与多巴胺 "关闭 "状态下的非冻结者相比,帕金森病冻结者在静息状态下的前三角-边缘回路功能失调。虽然其他研究发现多巴胺能替代疗法改变了帕金森病患者的大脑功能组织,但多巴胺药物对冷冻患者前三角-边缘功能连接的具体影响仍不清楚:目的:评估多巴胺治疗如何改变PD冰冻症患者前三角-边缘回路的静息状态功能连通性(rsFC),以及连通性的改变程度是否与冰冻严重程度和焦虑有关:方法:23 名 PD FOG 患者在临床定义的多巴胺能药物 "关闭 "和 "开启 "状态下接受了静息 MRI(rsfMRI)检查。在先验定义的边缘回路 ROI 之间进行了基于种子到种子的分析。比较了 "关 "和 "开 "状态之间的功能连接性。二次相关分析评估了医院焦虑和抑郁量表(HADS)-焦虑)和 FOG 问卷与 rsFC 从 OFF 到 ON 的变化之间的关系:结果发现:与开启相比,PD 冻结者的关闭状态显示右侧海马和右侧尾状核之间的功能耦合增加,而左侧丘脑和左侧后顶叶皮层(PPC)之间的功能耦合增加。结论:HADS-焦虑与左侧杏仁核和左侧前额叶皮层之间以及左侧丘脑和左侧后顶叶皮层之间的rsFC从 "关闭 "到 "开启 "的变化之间存在负相关:这些研究结果表明,多巴胺能药物部分调节了帕金森氏症冷冻患者的额顶叶-边缘-纹状体回路,而药物对杏仁核的影响可能与冷冻患者的临床焦虑有关。
{"title":"Effect of dopamine on limbic network connectivity at rest in Parkinson's disease patients with freezing of gait.","authors":"Dione Y L Quek, Natasha Taylor, Moran Gilat, Simon J G Lewis, Kaylena A Ehgoetz Martens","doi":"10.1515/tnsci-2022-0336","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0336","url":null,"abstract":"<p><strong>Background: </strong>Freezing of gait (FOG) in Parkinson's disease (PD) has a poorly understood pathophysiology, which hinders treatment development. Recent work showed a dysfunctional fronto-striato-limbic circuitry at rest in PD freezers compared to non-freezers in the dopamine \"OFF\" state. While other studies found that dopaminergic replacement therapy alters functional brain organization in PD, the specific effect of dopamine medication on fronto-striato-limbic functional connectivity in freezers remains unclear.</p><p><strong>Objective: </strong>To evaluate how dopamine therapy alters resting state functional connectivity (rsFC) of the fronto-striato-limbic circuitry in PD freezers, and whether the degree of connectivity change is related to freezing severity and anxiety.</p><p><strong>Methods: </strong>Twenty-three PD FOG patients underwent MRI at rest (rsfMRI) in their clinically defined \"OFF\" and \"ON\" dopaminergic medication states. A seed-to-seed based analysis was performed between a priori defined limbic circuitry ROIs. Functional connectivity was compared between OFF and ON states. A secondary correlation analyses evaluated the relationship between Hospital Anxiety and Depression Scale (HADS)-Anxiety) and FOG Questionnaire with changes in rsFC from OFF to ON.</p><p><strong>Results: </strong>PD freezers' OFF compared to ON showed increased functional coupling between the right hippocampus and right caudate nucleus, and between the left putamen and left posterior parietal cortex (PPC). A negative association was found between HADS-Anxiety and the rsFC change from OFF to ON between the left amygdala and left prefrontal cortex, and left putamen and left PPC.</p><p><strong>Conclusion: </strong>These findings suggest that dopaminergic medication partially modulates the frontoparietal-limbic-striatal circuitry in PD freezers, and that the influence of medication on the amygdala, may be related to clinical anxiety in freezer.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220336"},"PeriodicalIF":2.1,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11066616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-24eCollection Date: 2024-01-01DOI: 10.1515/tnsci-2022-0339
Jintao Wu, Yue Zhao
The ventral bed nucleus of the stria terminalis (vBNST) plays a key role in cocaine addiction, especially relapse. However, the direct effects of cocaine on corticotropin-releasing hormone (CRH) neurons in the vBNST remain unclear. Here, we identify that cocaine exposure can remarkably attenuate the intrinsic excitability of CRH neurons in the vBNST in vitro. Accumulating studies reveal the crucial role of Sigma-1 receptors (Sig-1Rs) in modulating cocaine addiction. However, to the authors' best knowledge no investigations have explored the role of Sig-1Rs in the vBNST, let alone CRH neurons. Given that cocaine acts as a type of Sig-1Rs agonist, and the dramatic role of Sig-1Rs played in intrinsic excitability of neurons as well as cocaine addiction, we employ BD1063 a canonical Sig-1Rs antagonist to block the effects of cocaine, and significantly recover the excitability of CRH neurons. Together, we suggest that cocaine exposure leads to the firing rate depression of CRH neurons in the vBNST via binding to Sig-1Rs.
{"title":"Single cocaine exposure attenuates the intrinsic excitability of CRH neurons in the ventral BNST via Sigma-1 receptors.","authors":"Jintao Wu, Yue Zhao","doi":"10.1515/tnsci-2022-0339","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0339","url":null,"abstract":"<p><p>The ventral bed nucleus of the stria terminalis (vBNST) plays a key role in cocaine addiction, especially relapse. However, the direct effects of cocaine on corticotropin-releasing hormone (CRH) neurons in the vBNST remain unclear. Here, we identify that cocaine exposure can remarkably attenuate the intrinsic excitability of CRH neurons in the vBNST <i>in vitro</i>. Accumulating studies reveal the crucial role of Sigma-1 receptors (Sig-1Rs) in modulating cocaine addiction. However, to the authors' best knowledge no investigations have explored the role of Sig-1Rs in the vBNST, let alone CRH neurons. Given that cocaine acts as a type of Sig-1Rs agonist, and the dramatic role of Sig-1Rs played in intrinsic excitability of neurons as well as cocaine addiction, we employ BD1063 a canonical Sig-1Rs antagonist to block the effects of cocaine, and significantly recover the excitability of CRH neurons. Together, we suggest that cocaine exposure leads to the firing rate depression of CRH neurons in the vBNST via binding to Sig-1Rs.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220339"},"PeriodicalIF":2.1,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11047800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140855274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-11eCollection Date: 2024-01-01DOI: 10.1515/tnsci-2022-0334
Jing Cheng, Hong Yang, Fang Chen, Li Qiu, Fang Chen, Yanhua Du, Xiangping Meng
Background: Death among resuscitated patients is mainly caused by brain injury after cardiac arrest/cardiopulmonary resuscitation (CA/CPR). The angiotensin converting enzyme 2 (ACE2)/angiotensin (Ang)-(1-7)/Mas receptor (MasR) axis has beneficial effects on brain injury. Therefore, we examined the roles of the ACE2/Ang-(1-7)/MasR axis in brain injury after CA/CPR.
Method: We used a total of 76 male New Zealand rabbits, among which 10 rabbits underwent sham operation and 66 rabbits received CA/CPR. Neurological functions were determined by assessing serum levels of neuron-specific enolase and S100 calcium-binding protein B and neurological deficit scores. Brain water content was estimated. Neuronal apoptosis in the hippocampus was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling assays. The expression levels of various genes were measured by enzyme-linked immunosorbent assay and western blotting.
Results: Ang-(1-7) (MasR activator) alleviated CA/CPR-induced neurological deficits, brain edema, and neuronal damage, and A779 (MasR antagonist) had the opposite functions. The stimulation of ACE2/Ang-(1-7)/MasR inactivated the ACE/Ang II/AT1R axis and activated PI3K/Akt signaling. Inhibiting PI3K/Akt signaling inhibited Ang-(1-7)-mediated protection against brain damage after CA/CPR.
Conclusion: Collectively, the ACE2/Ang-(1-7)/MasR axis alleviates CA/CPR-induced brain injury through attenuating hippocampal neuronal apoptosis by activating PI3K/Akt signaling.
{"title":"The ACE2/Ang-(1-7)/MasR axis alleviates brain injury after cardiopulmonary resuscitation in rabbits by activating PI3K/Akt signaling.","authors":"Jing Cheng, Hong Yang, Fang Chen, Li Qiu, Fang Chen, Yanhua Du, Xiangping Meng","doi":"10.1515/tnsci-2022-0334","DOIUrl":"10.1515/tnsci-2022-0334","url":null,"abstract":"<p><strong>Background: </strong>Death among resuscitated patients is mainly caused by brain injury after cardiac arrest/cardiopulmonary resuscitation (CA/CPR). The angiotensin converting enzyme 2 (ACE2)/angiotensin (Ang)-(1-7)/Mas receptor (MasR) axis has beneficial effects on brain injury. Therefore, we examined the roles of the ACE2/Ang-(1-7)/MasR axis in brain injury after CA/CPR.</p><p><strong>Method: </strong>We used a total of 76 male New Zealand rabbits, among which 10 rabbits underwent sham operation and 66 rabbits received CA/CPR. Neurological functions were determined by assessing serum levels of neuron-specific enolase and S100 calcium-binding protein B and neurological deficit scores. Brain water content was estimated. Neuronal apoptosis in the hippocampus was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling assays. The expression levels of various genes were measured by enzyme-linked immunosorbent assay and western blotting.</p><p><strong>Results: </strong>Ang-(1-7) (MasR activator) alleviated CA/CPR-induced neurological deficits, brain edema, and neuronal damage, and A779 (MasR antagonist) had the opposite functions. The stimulation of ACE2/Ang-(1-7)/MasR inactivated the ACE/Ang II/AT1R axis and activated PI3K/Akt signaling. Inhibiting PI3K/Akt signaling inhibited Ang-(1-7)-mediated protection against brain damage after CA/CPR.</p><p><strong>Conclusion: </strong>Collectively, the ACE2/Ang-(1-7)/MasR axis alleviates CA/CPR-induced brain injury through attenuating hippocampal neuronal apoptosis by activating PI3K/Akt signaling.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220334"},"PeriodicalIF":1.8,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11017183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140865722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-10eCollection Date: 2024-01-01DOI: 10.1515/tnsci-2022-0338
Liangxian Li, Zhiheng Huang, Mingli Wu, Xia Li, Bo Xiao, Dong Yao, Biwen Mo
Background: The deposition of Aβ42 has been regarded as one of the important pathological features of Alzheimer's disease (AD). However, drug development for Aβ42 toxicity has been progressed slowly.
Objective: Our aim was to introduce the effect and related mechanism of trehalose on an Aβarc (arctic mutant Aβ42) Drosophila AD model.
Methods: The human Aβarc was expressed in Drosophila to construct the AD model. Trehalose was added to the culture vial. The movement ability was determined by detecting climbing ability and flight ability. Enzyme-linked immunosorbent assay was used to detect the levels of Aβarc, ATP, and lactate. Electron microscopy assay, mitochondrial membrane potential assay, and mitochondrial respiration assay were used to assess the mitochondrial structure and function.
Results: Trehalose strongly improved the movement ability of AβarcDrosophila in a concentration gradient-dependent manner. Furthermore, trehalose increased the content of ATP and decreased the content of Aβarc and lactate both in the brain and thorax of AβarcDrosophila. More importantly, the mitochondrial structure and function were greatly improved by trehalose treatment in AβarcDrosophila.
Conclusion: Trehalose improves movement ability at least partly by reducing the Aβarc level and restoring the mitochondrial structure and function in AβarcDrosophila.
背景:Aβ42 的沉积一直被认为是阿尔茨海默病(AD)的重要病理特征之一。然而,针对 Aβ42 毒性的药物开发进展缓慢:我们的目的是介绍三卤糖对 Aβarc(北极突变体 Aβ42)果蝇 AD 模型的影响及相关机制:方法:在果蝇中表达人Aβarc,构建AD模型。方法:在果蝇体内表达人 Aβarc 以构建 AD 模型。通过检测爬行能力和飞行能力来确定果蝇的运动能力。酶联免疫吸附试验检测 Aβarc、ATP 和乳酸的水平。电镜检测、线粒体膜电位检测和线粒体呼吸检测用于评估线粒体结构和功能:结果:在浓度梯度依赖性作用下,曲哈洛糖能显著提高 Aβarc 果蝇的运动能力。此外,在 Aβarc 果蝇的大脑和胸部,三卤糖都能增加 ATP 的含量,降低 Aβarc 和乳酸的含量。更重要的是,经曲阿露糖处理的 Aβarc 果蝇的线粒体结构和功能得到了极大改善:结论:通过降低 Aβarc 水平和恢复 Aβarc 果蝇的线粒体结构和功能,树胶糖至少部分改善了果蝇的运动能力。
{"title":"Trehalose improves the movement ability of Aβ<sub>arc</sub><i>Drosophila</i> by restoring the damaged mitochondria.","authors":"Liangxian Li, Zhiheng Huang, Mingli Wu, Xia Li, Bo Xiao, Dong Yao, Biwen Mo","doi":"10.1515/tnsci-2022-0338","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0338","url":null,"abstract":"<p><strong>Background: </strong>The deposition of Aβ<sub>42</sub> has been regarded as one of the important pathological features of Alzheimer's disease (AD). However, drug development for Aβ<sub>42</sub> toxicity has been progressed slowly.</p><p><strong>Objective: </strong>Our aim was to introduce the effect and related mechanism of trehalose on an Aβ<sub>arc</sub> (arctic mutant Aβ<sub>42</sub>) <i>Drosophila</i> AD model.</p><p><strong>Methods: </strong>The human Aβ<sub>arc</sub> was expressed in <i>Drosophila</i> to construct the AD model. Trehalose was added to the culture vial. The movement ability was determined by detecting climbing ability and flight ability. Enzyme-linked immunosorbent assay was used to detect the levels of Aβ<sub>arc</sub>, ATP, and lactate. Electron microscopy assay, mitochondrial membrane potential assay, and mitochondrial respiration assay were used to assess the mitochondrial structure and function.</p><p><strong>Results: </strong>Trehalose strongly improved the movement ability of Aβ<sub>arc</sub> <i>Drosophila</i> in a concentration gradient-dependent manner. Furthermore, trehalose increased the content of ATP and decreased the content of Aβ<sub>arc</sub> and lactate both in the brain and thorax of Aβ<sub>arc</sub> <i>Drosophila</i>. More importantly, the mitochondrial structure and function were greatly improved by trehalose treatment in Aβ<sub>arc</sub> <i>Drosophila</i>.</p><p><strong>Conclusion: </strong>Trehalose improves movement ability at least partly by reducing the Aβ<sub>arc</sub> level and restoring the mitochondrial structure and function in Aβ<sub>arc</sub> <i>Drosophila</i>.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220338"},"PeriodicalIF":2.1,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11017185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140868193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-05eCollection Date: 2024-01-01DOI: 10.1515/tnsci-2022-0337
Jing Liu, Gaoning Wang, Jiahe Yang, Yulin Wang, Ruoyi Guo, Bin Li
<p><strong>Background: </strong>Forkhead box P3 (<i>FOXP3</i>) plays a critical role in the pathogenesis of autoimmune disorders. In the present study, we genotyped three single-nucleotide polymorphisms, namely, rs2232365, rs3761548, and rs3761549, to determine the relationship between <i>FOXP3</i> polymorphisms and neuromyelitis optica spectrum disorder (NMOSD) susceptibility among the Northern Chinese Han population.</p><p><strong>Materials and methods: </strong>We genotyped single nucleotide polymorphisms at loci of the <i>FOXP3</i> gene (rs2232365, rs3761548, and rs3761549136) in 136 NMOSD patients and 224 healthy subjects using the multiplex SNaPshot technique. Allele, genotype, and haplotype frequencies were compared. qPCR was used to analyze the mRNA expression levels of <i>FOXP3</i> in the peripheral blood mononuclear cells of 63 NMOSD patients and 35 healthy subjects. Non-parametric tests were used to test the FOXP3 mRNA expression across the different groups.</p><p><strong>Results: </strong>The minor allele frequency (MAF) of G in rs2232365 was markedly lower in the NMOSD group than in the control group (odds ratio [OR] = 0.57, 95% confidence interval [95% CI]: 0.41-0.79, <i>p</i> = 0.001). Using genetic (codominant, dominant, and recessive) models and performing haplotype analyses, the MAF of G in rs2232365 was shown to be associated with protection against NMOSD in this population. Furthermore, haplotype analysis revealed that the haplotype GCT and the rs2232365, rs3761548, and rs3761549 alleles predicted protection against NMOSD (OR = 0.63, 95% CI = 0.41-0.97, <i>p</i> = 0.038). The proportions of the three genotypes of rs2232365 (<i>p</i> = 0.001) were not significantly different between the moderate-to-severe (Expanded Disability Status Scale (EDSS) ≥ 3 points) and mild (EDSS < 3 points) groups. Evidently, the proportion of patients with the AA genotype (64.3%) among the rs2232365 patients was significantly greater in the moderate-to-severe group than in the mild group (36.4%). However, the proportion of patients with the GG genotype (15.2%) among the rs2232365 patients was significantly greater in the mild group than in the moderate-to-severe group (2.9%). The mRNA expression of <i>FOXP3</i> was markedly greater in the NMOSD group than in the control group (<i>p</i> = 0.001). Nevertheless, acute non-treatment patients exhibited lower FOXP3 mRNA expression than healthy controls and patients in the remission group (<i>p</i> = 0.004 and 0.007, respectively).</p><p><strong>Conclusion: </strong><i>FOXP3</i> polymorphisms and haplotypes are related to NMOSD susceptibility among the Han Chinese population. The minor allele G of <i>FOXP3</i> rs2232365 and the haplotype GCT are associated with protection against NMOSD. The GG genotype may decrease the severity of NMOSD, whereas the AA genotype is related to moderate-to-severe NMOSD. <i>FOXP3</i> mRNA expression is greater in patients with NMOSD than in healthy controls. However, it is decr
{"title":"Association between <i>FOXP3</i> polymorphisms and expression and neuromyelitis optica spectrum disorder risk in the Northern Chinese Han population.","authors":"Jing Liu, Gaoning Wang, Jiahe Yang, Yulin Wang, Ruoyi Guo, Bin Li","doi":"10.1515/tnsci-2022-0337","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0337","url":null,"abstract":"<p><strong>Background: </strong>Forkhead box P3 (<i>FOXP3</i>) plays a critical role in the pathogenesis of autoimmune disorders. In the present study, we genotyped three single-nucleotide polymorphisms, namely, rs2232365, rs3761548, and rs3761549, to determine the relationship between <i>FOXP3</i> polymorphisms and neuromyelitis optica spectrum disorder (NMOSD) susceptibility among the Northern Chinese Han population.</p><p><strong>Materials and methods: </strong>We genotyped single nucleotide polymorphisms at loci of the <i>FOXP3</i> gene (rs2232365, rs3761548, and rs3761549136) in 136 NMOSD patients and 224 healthy subjects using the multiplex SNaPshot technique. Allele, genotype, and haplotype frequencies were compared. qPCR was used to analyze the mRNA expression levels of <i>FOXP3</i> in the peripheral blood mononuclear cells of 63 NMOSD patients and 35 healthy subjects. Non-parametric tests were used to test the FOXP3 mRNA expression across the different groups.</p><p><strong>Results: </strong>The minor allele frequency (MAF) of G in rs2232365 was markedly lower in the NMOSD group than in the control group (odds ratio [OR] = 0.57, 95% confidence interval [95% CI]: 0.41-0.79, <i>p</i> = 0.001). Using genetic (codominant, dominant, and recessive) models and performing haplotype analyses, the MAF of G in rs2232365 was shown to be associated with protection against NMOSD in this population. Furthermore, haplotype analysis revealed that the haplotype GCT and the rs2232365, rs3761548, and rs3761549 alleles predicted protection against NMOSD (OR = 0.63, 95% CI = 0.41-0.97, <i>p</i> = 0.038). The proportions of the three genotypes of rs2232365 (<i>p</i> = 0.001) were not significantly different between the moderate-to-severe (Expanded Disability Status Scale (EDSS) ≥ 3 points) and mild (EDSS < 3 points) groups. Evidently, the proportion of patients with the AA genotype (64.3%) among the rs2232365 patients was significantly greater in the moderate-to-severe group than in the mild group (36.4%). However, the proportion of patients with the GG genotype (15.2%) among the rs2232365 patients was significantly greater in the mild group than in the moderate-to-severe group (2.9%). The mRNA expression of <i>FOXP3</i> was markedly greater in the NMOSD group than in the control group (<i>p</i> = 0.001). Nevertheless, acute non-treatment patients exhibited lower FOXP3 mRNA expression than healthy controls and patients in the remission group (<i>p</i> = 0.004 and 0.007, respectively).</p><p><strong>Conclusion: </strong><i>FOXP3</i> polymorphisms and haplotypes are related to NMOSD susceptibility among the Han Chinese population. The minor allele G of <i>FOXP3</i> rs2232365 and the haplotype GCT are associated with protection against NMOSD. The GG genotype may decrease the severity of NMOSD, whereas the AA genotype is related to moderate-to-severe NMOSD. <i>FOXP3</i> mRNA expression is greater in patients with NMOSD than in healthy controls. However, it is decr","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220337"},"PeriodicalIF":2.1,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10998649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-22eCollection Date: 2024-01-01DOI: 10.1515/tnsci-2022-0327
Tingting An, Zibei Dong, Xiangyang Li, Yifan Ma, Jie Jin, Liqing Li, Lanjuan Xu
Background: Both the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) and the Corticosteroid randomization after significant head injury (CRASH) models are globally acknowledged prognostic algorithms for assessing traumatic brain injury (TBI) outcomes. The aim of this study is to externalize the validation process and juxtapose the prognostic accuracy of the CRASH and IMPACT models in moderate-to-severe TBI patients in the Chinese population.
Methods: We conducted a retrospective study encompassing a cohort of 340 adult TBI patients (aged > 18 years), presenting with Glasgow Coma Scale (GCS) scores ranging from 3 to 12. The data were accrued over 2 years (2020-2022). The primary endpoints were 14-day mortality rates and 6-month Glasgow Outcome Scale (GOS) scores. Analytical metrics, including the area under the receiver operating characteristic curve for discrimination and the Brier score for predictive precision were employed to quantitatively evaluate the model performance.
Results: Mortality rates at the 14-day and 6-month intervals, as well as the 6-month unfavorable GOS outcomes, were established to be 22.06, 40.29, and 65.59%, respectively. The IMPACT models had area under the curves (AUCs) of 0.873, 0.912, and 0.927 for the 6-month unfavorable GOS outcomes, with respective Brier scores of 0.14, 0.12, and 0.11. On the other hand, the AUCs associated with the six-month mortality were 0.883, 0.909, and 0.912, and the corresponding Brier scores were 0.15, 0.14, and 0.13, respectively. The CRASH models exhibited AUCs of 0.862 and 0.878 for the 6-month adverse outcomes, with uniform Brier scores of 0.18. The 14-day mortality rates had AUCs of 0.867 and 0.87, and corresponding Brier scores of 0.21 and 0.22, respectively.
Conclusion: Both the CRASH and IMPACT algorithms offer reliable prognostic estimations for patients suffering from craniocerebral injuries. However, compared to the CRASH model, the IMPACT model has superior predictive accuracy, albeit at the cost of increased computational intricacy.
{"title":"Comparative analysis of CRASH and IMPACT in predicting the outcome of 340 patients with traumatic brain injury.","authors":"Tingting An, Zibei Dong, Xiangyang Li, Yifan Ma, Jie Jin, Liqing Li, Lanjuan Xu","doi":"10.1515/tnsci-2022-0327","DOIUrl":"10.1515/tnsci-2022-0327","url":null,"abstract":"<p><strong>Background: </strong>Both the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) and the Corticosteroid randomization after significant head injury (CRASH) models are globally acknowledged prognostic algorithms for assessing traumatic brain injury (TBI) outcomes. The aim of this study is to externalize the validation process and juxtapose the prognostic accuracy of the CRASH and IMPACT models in moderate-to-severe TBI patients in the Chinese population.</p><p><strong>Methods: </strong>We conducted a retrospective study encompassing a cohort of 340 adult TBI patients (aged > 18 years), presenting with Glasgow Coma Scale (GCS) scores ranging from 3 to 12. The data were accrued over 2 years (2020-2022). The primary endpoints were 14-day mortality rates and 6-month Glasgow Outcome Scale (GOS) scores. Analytical metrics, including the area under the receiver operating characteristic curve for discrimination and the Brier score for predictive precision were employed to quantitatively evaluate the model performance.</p><p><strong>Results: </strong>Mortality rates at the 14-day and 6-month intervals, as well as the 6-month unfavorable GOS outcomes, were established to be 22.06, 40.29, and 65.59%, respectively. The IMPACT models had area under the curves (AUCs) of 0.873, 0.912, and 0.927 for the 6-month unfavorable GOS outcomes, with respective Brier scores of 0.14, 0.12, and 0.11. On the other hand, the AUCs associated with the six-month mortality were 0.883, 0.909, and 0.912, and the corresponding Brier scores were 0.15, 0.14, and 0.13, respectively. The CRASH models exhibited AUCs of 0.862 and 0.878 for the 6-month adverse outcomes, with uniform Brier scores of 0.18. The 14-day mortality rates had AUCs of 0.867 and 0.87, and corresponding Brier scores of 0.21 and 0.22, respectively.</p><p><strong>Conclusion: </strong>Both the CRASH and IMPACT algorithms offer reliable prognostic estimations for patients suffering from craniocerebral injuries. However, compared to the CRASH model, the IMPACT model has superior predictive accuracy, albeit at the cost of increased computational intricacy.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220327"},"PeriodicalIF":2.1,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10961482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140289086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}