Pub Date : 2024-11-05DOI: 10.1016/j.neuroscience.2024.11.002
Dirk De Ridder , Sven Vanneste
A common anatomical core has been described for psychiatric disorders, consisting of the dorsal anterior cingulate cortex (dACC) and anterior insula, processing uncertainty. A common neurophysiological core has been described for other brain related disorders, called thalamocortical dysrhythmia (TCD), consisting of persistent cross-frequency coupling between low and high frequencies. And a common genetic core has been described for yet another set of hypodopaminergic pathologies called reward deficiency syndromes (RDS). Considering that some RDS have the neurophysiological features of TCD, it can be hypothesized that TCD and RDS have a common anatomical core, yet a differentiating associated neurophysiological mechanism. The EEGs of 683 subjects are analysed in source space for both differences and conjunction between TCD and healthy controls, RDS and healthy controls, and between TCD and RDS. A balance between current densities of the pregenual anterior cingulate cortex (pgACC) extending into the ventromedial prefrontal cortex (vmPFC) and dACC is calculated as well. TCD and RDS share a common anatomical and neurophysiological core, consisting of beta activity in the dACC and theta activity in dACC extending into precuneus and dorsolateral prefrontal cortex. TCD and RDS differ in pgACC/vmPFC activity and demonstrate an opposite balance between pgACC/vmPFC and dACC. Based on the Bayesian brain model TCD and RDS can be defined as uncertainty disorders in which the pgACC/vmPFC and dACC have an opposite balance, possibly explained by an inverted-U curve profile of both pgACC/vmPFC and dACC.
{"title":"Thalamocortical dysrhythmia and reward deficiency syndrome as uncertainty disorders","authors":"Dirk De Ridder , Sven Vanneste","doi":"10.1016/j.neuroscience.2024.11.002","DOIUrl":"10.1016/j.neuroscience.2024.11.002","url":null,"abstract":"<div><div>A common <em>anatomical</em> core has been described for psychiatric disorders, consisting of the dorsal anterior cingulate cortex (dACC) and anterior insula, processing uncertainty. A common <em>neurophysiological</em> core has been described for other brain related disorders, called thalamocortical dysrhythmia (TCD), consisting of persistent cross-frequency coupling between low and high frequencies. And a common <em>genetic</em> core has been described for yet another set of hypodopaminergic pathologies called reward deficiency syndromes (RDS). Considering that some RDS have the neurophysiological features of TCD, it can be hypothesized that TCD and RDS have a common anatomical core, yet a differentiating associated neurophysiological mechanism. The EEGs of 683 subjects are analysed in source space for both differences and conjunction between TCD and healthy controls, RDS and healthy controls, and between TCD and RDS. A balance between current densities of the pregenual anterior cingulate cortex (pgACC) extending into the ventromedial prefrontal cortex (vmPFC) and dACC is calculated as well. TCD and RDS share a common anatomical and neurophysiological core, consisting of beta activity in the dACC and theta activity in dACC extending into precuneus and dorsolateral prefrontal cortex. TCD and RDS differ in pgACC/vmPFC activity and demonstrate an opposite balance between pgACC/vmPFC and dACC. Based on the Bayesian brain model TCD and RDS can be defined as uncertainty disorders in which the pgACC/vmPFC and dACC have an opposite balance, possibly explained by an inverted-U curve profile of both pgACC/vmPFC and dACC.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"563 ","pages":"Pages 20-32"},"PeriodicalIF":2.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-05DOI: 10.1016/j.neuroscience.2024.11.004
Xingli Tan , Xiaoli Su , Ying Wang , Weiwei Liang , Di Wang , Di Huo , Hongyong Wang , Yan Qi , Wenmo Zhang , Ling Han , Dongmei Zhang , Ming Wang , Jing Xu , Honglin Feng
Cellular senescence is involved in the progression of neurodegenerative diseases. Motor neurons exhibit senescence-like alterations in ALS. BRD7, identified as a regulatory factor associated with cellular senescence, its function in ALS remains unclear. This study aims to investigate the potential role and mechanisms of BRD7 in ALS. We analyzed RNA levels using qRT-PCR, protein levels through immunofluorescence and western blot, and apoptosis via TUNEL staining. Cell transfection was conducted for in vitro experiments. The level of β-galactosidase was measured by β-galactosidase activity detection kit. ALS motor neurons exhibited senescence-like alterations, characterized by increased activity of p53, p21, and β-galactosidase, as well as reduced lamin B1 staining. Additionally, the expression of BRD7 was upregulated and induced cellular senescence and apoptosis. Downregulation of BRD7 alleviates the cellular senescence by inhibiting p21 rather than p53. Knockdown of BRD7 inhibited p53 mitochondrial translocation, leading to reduced apoptosis. Our results suggest that BRD7 plays an important role in the survival of ALS motor neurons. BRD7 knockdown can reduce cellular senescence and apoptosis by inhibiting p21 and p53 mitochondrial translocation.
细胞衰老与神经退行性疾病的进展有关。肌萎缩性脊髓侧索硬化症的运动神经元表现出衰老样改变。BRD7被确定为与细胞衰老相关的调控因子，但其在ALS中的功能仍不清楚。本研究旨在探讨 BRD7 在 ALS 中的潜在作用和机制。我们通过 qRT-PCR 分析了 RNA 水平，通过免疫荧光和 Western 印迹分析了蛋白质水平，通过 TUNEL 染色分析了细胞凋亡。体外实验中进行了细胞转染。用β-半乳糖苷酶活性检测试剂盒检测β-半乳糖苷酶的水平。ALS 运动神经元表现出衰老样改变，其特征是 p53、p21 和 β-半乳糖苷酶活性增加，以及片层 B1 染色减少。此外，BRD7 的表达上调并诱导细胞衰老和凋亡。下调BRD7可通过抑制p21而不是p53来缓解细胞衰老。敲除BRD7可抑制p53线粒体转位，从而减少细胞凋亡。我们的研究结果表明，BRD7在ALS运动神经元的存活过程中发挥着重要作用。敲除BRD7可通过抑制p21和p53线粒体转位减少细胞衰老和凋亡。
{"title":"BRD7 regulates cellular senescence and apoptosis in ALS by modulating p21 expression and p53 mitochondrial translocation respectively","authors":"Xingli Tan , Xiaoli Su , Ying Wang , Weiwei Liang , Di Wang , Di Huo , Hongyong Wang , Yan Qi , Wenmo Zhang , Ling Han , Dongmei Zhang , Ming Wang , Jing Xu , Honglin Feng","doi":"10.1016/j.neuroscience.2024.11.004","DOIUrl":"10.1016/j.neuroscience.2024.11.004","url":null,"abstract":"<div><div>Cellular senescence is involved in the progression of neurodegenerative diseases. Motor neurons exhibit senescence-like alterations in ALS. BRD7, identified as a regulatory factor associated with cellular senescence, its function in ALS remains unclear. This study aims to investigate the potential role and mechanisms of BRD7 in ALS. We analyzed RNA levels using qRT-PCR, protein levels through immunofluorescence and western blot, and apoptosis via TUNEL staining. Cell transfection was conducted for in vitro experiments. The level of β-galactosidase was measured by β-galactosidase activity detection kit. ALS motor neurons exhibited senescence-like alterations, characterized by increased activity of p53, p21, and β-galactosidase, as well as reduced lamin B1 staining. Additionally, the expression of BRD7 was upregulated and induced cellular senescence and apoptosis. Downregulation of BRD7 alleviates the cellular senescence by inhibiting p21 rather than p53. Knockdown of BRD7 inhibited p53 mitochondrial translocation, leading to reduced apoptosis. Our results suggest that BRD7 plays an important role in the survival of ALS motor neurons. BRD7 knockdown can reduce cellular senescence and apoptosis by inhibiting p21 and p53 mitochondrial translocation.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"563 ","pages":"Pages 51-62"},"PeriodicalIF":2.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-04DOI: 10.1016/j.neuroscience.2024.11.001
Yufei Zhao , Lei Zhao , Fei Yang , Chunjing Tao , Weizhong Tang , Wenming Cheng , Yu Zhang , Lingguo Bu
In recent years, the incidence rate of children with autism has shown a significant upward trend. Rehabilitation training is an important part of recovery or improvement in autism children. However, during autism rehabilitation training, the methods that can visually reflect and objectively evaluate its effects are seldom considered. Therefore, this study aimed to objectively evaluate the rehabilitation impact of visual-motor skills training in children with autism via quantitative measures. In this study, vision sensors and functional near-infrared spectroscopy were used to monitor and analyze visual motor training task of 20 autism children. These children were divided into high- and low-score groups according to the autism behavior checklist (ABC). Results showed significant differences between the high- and low-score groups in the brain regions of the left and right temporal lobe, right motor cortex, and left occipital lobe; the difference in functional connectivity was greatest when the left hand was moving at the green light (p < 0.05). The differences in speed, acceleration, and angle between the high- and low-score groups were mainly reflected in left-hand movement. Moreover, analysis of multimodal data showed that visual motor training had a positive effect on brain activation and functional connectivity, and increasing the frequency of left-hand training and using more green light were beneficial to the improvement of brain function. These findings can be used as basis to help optimize rehabilitation programs and improve rehabilitation effectiveness.
{"title":"Assessing visual motor performance in autistic children based on Kinect and fNIRS: A case study","authors":"Yufei Zhao , Lei Zhao , Fei Yang , Chunjing Tao , Weizhong Tang , Wenming Cheng , Yu Zhang , Lingguo Bu","doi":"10.1016/j.neuroscience.2024.11.001","DOIUrl":"10.1016/j.neuroscience.2024.11.001","url":null,"abstract":"<div><div>In recent years, the incidence rate of children with autism has shown a significant upward trend. Rehabilitation training is an important part of recovery or improvement in autism children. However, during autism rehabilitation training, the methods that can visually reflect and objectively evaluate its effects are seldom considered. Therefore, this study aimed to objectively evaluate the rehabilitation impact of visual-motor skills training in children with autism via quantitative measures. In this study, vision sensors and functional near-infrared spectroscopy were used to monitor and analyze visual motor training task of 20 autism children. These children were divided into high- and low-score groups according to the autism behavior checklist (ABC). Results showed significant differences between the high- and low-score groups in the brain regions of the left and right temporal lobe, right motor cortex, and left occipital lobe; the difference in functional connectivity was greatest when the left hand was moving at the green light (p < 0.05). The differences in speed, acceleration, and angle between the high- and low-score groups were mainly reflected in left-hand movement. Moreover, analysis of multimodal data showed that visual motor training had a positive effect on brain activation and functional connectivity, and increasing the frequency of left-hand training and using more green light were beneficial to the improvement of brain function. These findings can be used as basis to help optimize rehabilitation programs and improve rehabilitation effectiveness.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"563 ","pages":"Pages 10-19"},"PeriodicalIF":2.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adipokines are proposed to be associated with ALS progression through assorted pathways. Therefore, The present meta-analysis explored the link between various adipokines and ALS progression.
Method
International database like PubMed, Scopus, and Web of Science databases were searched to achieve eligible papers published before December 2023. The following PICO structure was utilized: Population (patients with ALS); Intervention (serum concentrations of ghrelin, leptin, and adiponectin), Comparison (with or without controls), and Outcome (ALS progression). the risk of bias of selected papers was assessed through the Newcastle-Ottawa Scale (NOS) tool.
Results
11 out of 240 papers were selected for this study which were published between 2010 and 2024. Lower serum leptin concentrations were detected in the ALS compared to control groups (WMD: −0.91, 95% CI:-1.77, −0.05). Serum concentrations of adiponectin were higher in ALS compared to control groups (WMD: 0.41, 95% CI:-0.7, 0.89). Ultimately, The serum concentrations of ghrelin in the ALS groups were lower than control groups (WMD: −1.21, 95% CI: −2.95, 0.53).
Conclusion
Our findings revealed that serum concentrations of ghrelin and leptin were higher in ALS patients compared to control, unlike adiponectin.
背景：脂肪因子被认为通过各种途径与 ALS 的进展相关。因此，本荟萃分析探讨了各种脂肪因子与 ALS 进展之间的联系：方法：检索 PubMed、Scopus 和 Web of Science 等国际数据库，以获得 2023 年 12 月之前发表的符合条件的论文。采用以下 PICO 结构：通过纽卡斯尔-渥太华量表（Newcastle-Ottawa Scale，NOS）工具对所选论文的偏倚风险进行评估：本研究从 240 篇论文中选取了 11 篇，这些论文发表于 2010 年至 2024 年之间。与对照组相比，ALS患者的血清瘦素浓度较低（WMD：-0.91，95% CI：-1.77，-0.05）。与对照组相比，ALS患者血清中的脂肪连素浓度更高（WMD：0.41，95% CI：-0.7，0.89）。最后，ALS 组血清中胃泌素的浓度低于对照组（WMD：-1.21，95% CI：-2.95，0.53）：我们的研究结果表明，与对照组相比，ALS 患者血清中胃泌素和瘦素的浓度较高，而脂肪连通素则不同。
{"title":"Unveiling the veil of adipokines: A meta-analysis and systematic review in amyotrophic lateral sclerosis","authors":"Hamid Abbasi , Neda Jourabchi-ghadim , Ali Asgarzade , Mobin Mirshekari , Mehrangiz Ebrahimi-Mameghani","doi":"10.1016/j.neuroscience.2024.11.003","DOIUrl":"10.1016/j.neuroscience.2024.11.003","url":null,"abstract":"<div><h3>Background</h3><div>Adipokines are proposed to be associated with ALS progression through assorted pathways. Therefore, The present <em>meta</em>-analysis explored the link between various adipokines and ALS progression.</div></div><div><h3>Method</h3><div>International database like PubMed, Scopus, and Web of Science databases were searched to achieve eligible papers published before December 2023. The following PICO structure was utilized: Population (patients with ALS); Intervention (serum concentrations of ghrelin, leptin, and adiponectin), Comparison (with or without controls), and Outcome (ALS progression). the risk of bias of selected papers was assessed through the Newcastle-Ottawa Scale (NOS) tool.</div></div><div><h3>Results</h3><div>11 out of 240 papers were selected for this study which were published between 2010 and 2024. Lower serum leptin concentrations were detected in the ALS compared to control groups (WMD: −0.91, 95% CI:-1.77, −0.05). Serum concentrations of adiponectin were higher in ALS compared to control groups (WMD: 0.41, 95% CI:-0.7, 0.89). Ultimately, The serum concentrations of ghrelin in the ALS groups were lower than control groups (WMD: −1.21, 95% CI: −2.95, 0.53).</div></div><div><h3>Conclusion</h3><div>Our findings revealed that serum concentrations of ghrelin and leptin were higher in ALS patients compared to control, unlike adiponectin.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"563 ","pages":"Pages 1-9"},"PeriodicalIF":2.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: This study aims to delve into the mechanisms underlying the improvement of neurological function in rats with ischemic stroke through fecal microbiota transplantation.
Methods: A total of fifty male Sprague-Dawley rats were categorized into three groups: sham surgery, model, and fecal transplantation. We assessed behavioral and pathological alterations in the rats using modified neurological function scoring and TTC staining. Additionally, Western blot and immunofluorescence techniques were employed to examine the expression levels of RIP1, RIP3, MLKL, p-MLKL, Bcl-2, Bax, and cleaved caspase-3 in neurons of ischemic brain tissue, while iNOS and Arg1 were analyzed to evaluate microglial polarization.
Results: The fecal transplantation group exhibited a decline in neurological function score compared to the model group, accompanied by a reduction in infarct volume (P < 0.05). Relative to the sham surgery group, the model group displayed a significant increase in the expression levels of necroptosis-related proteins RIP1, RIP3, p-MLKL, apoptotic proteins Bax and cleaved caspase-3, and the M1 microglial cell marker iNOS in ischemic brain tissue, while Bcl-2 expression was notably decreased (P < 0.05). Conversely, compared to the model group, the fecal transplantation group demonstrated decreased expression levels of RIP1, RIP3, p-MLKL, Bax, cleaved caspase-3, and iNOS, along with increased expression of Bcl-2.
Conclusion: Fecal microbiota transplantation presents a promising avenue for enhancing neurological function in rats with ischemic stroke by inhibiting neuronal apoptosis, necroptosis, and M1 polarization of microglial cells.
{"title":"Fecal microbiota transplantation alleviates neuronal Apoptosis, necroptosis and M1 polarization of microglia after ischemic stroke.","authors":"Dingzhi Chen, Jieqiong Xie, Xueyuan Chen, Biyun Qin, Deyan Kong, Jiefeng Luo","doi":"10.1016/j.neuroscience.2024.10.053","DOIUrl":"https://doi.org/10.1016/j.neuroscience.2024.10.053","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to delve into the mechanisms underlying the improvement of neurological function in rats with ischemic stroke through fecal microbiota transplantation.</p><p><strong>Methods: </strong>A total of fifty male Sprague-Dawley rats were categorized into three groups: sham surgery, model, and fecal transplantation. We assessed behavioral and pathological alterations in the rats using modified neurological function scoring and TTC staining. Additionally, Western blot and immunofluorescence techniques were employed to examine the expression levels of RIP1, RIP3, MLKL, p-MLKL, Bcl-2, Bax, and cleaved caspase-3 in neurons of ischemic brain tissue, while iNOS and Arg1 were analyzed to evaluate microglial polarization.</p><p><strong>Results: </strong>The fecal transplantation group exhibited a decline in neurological function score compared to the model group, accompanied by a reduction in infarct volume (P < 0.05). Relative to the sham surgery group, the model group displayed a significant increase in the expression levels of necroptosis-related proteins RIP1, RIP3, p-MLKL, apoptotic proteins Bax and cleaved caspase-3, and the M1 microglial cell marker iNOS in ischemic brain tissue, while Bcl-2 expression was notably decreased (P < 0.05). Conversely, compared to the model group, the fecal transplantation group demonstrated decreased expression levels of RIP1, RIP3, p-MLKL, Bax, cleaved caspase-3, and iNOS, along with increased expression of Bcl-2.</p><p><strong>Conclusion: </strong>Fecal microbiota transplantation presents a promising avenue for enhancing neurological function in rats with ischemic stroke by inhibiting neuronal apoptosis, necroptosis, and M1 polarization of microglial cells.</p>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alzheimer’s disease (AD) is the most common form of neurodegeneration that results in memory disorders and cognitive impairment. The present study investigated the neuroprotective effects of the synthesized thiazolidine-2,4-dione derivative, (E)-5-(4-chlorobenzylidene)-3-(2-oxo-2-phenylethyl)thiazolidine-2,4-dione (TZ4C), an inhibitor of p-Tau and memory impairment, using a SH-SY5Y cell model of methamphetamine-induced tauopathy and a scopolamine-induced memory impairment model in Wistar rats.
In the present study, the neuroprotective effect of TZ4C was studied in a SH-SY5Y cellular model of methamphetamine-induced (2 mM) tauopathy and a scopolamine-induced (1.5 mg/kg/day) memory impairment model in male Wistar rats (n = 48). The memory functions and learning abilities of the rats were evaluated using the Morris water maze (MWM) and passive avoidance tests. Additionally, AChE activity in the rat hippocampus was quantified, and the expression of p-Tau, HSP70, and caspase-3 in both in vitro and in vivo samples was evaluated through Western blot analysis.
TZ4C (0.1–1000 µM) did not exhibit significantly toxic effects on SH-SY5Y cell viability. Western blot results indicated that TZ4C led to reduced expression of p-Tau, HSP70, and cleaved caspase-3 in SH-SY5Y cells (3 and 10 µM) and the rat hippocampus (2 and 4 mg/kg). Additionally, the findings suggested that TZ4C enhanced memory function in rats with scopolamine-induced impairment and decreased acetylcholinesterase (AChE) specific activity.
The comprehensive analysis of in vitro and in vivo experiments underscores the neuroprotective potential (improved neuropathology and reduced memory impairment) of TZ4C. These findings highlight the promise of TZ4C as a candidate for drug discovery programs to identify effective therapies for AD.
{"title":"Neuroprotective properties of a thiazolidine-2,4-dione derivative as an inhibitory agent against memory impairment and phosphorylated tau: In vitro and in vivo investigations","authors":"Maryam Taheri , Mohammad Hadi Moradi , Yasaman Koraee , Farshad Homayouni Moghadam , Seyed Ershad Nedaei , Mojgan Veisi , Hossein Ghafouri","doi":"10.1016/j.neuroscience.2024.10.054","DOIUrl":"10.1016/j.neuroscience.2024.10.054","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is the most common form of neurodegeneration that results in memory disorders and cognitive impairment. The present study investigated the neuroprotective effects of the synthesized thiazolidine-2,4-dione derivative, (E)-5-(4-chlorobenzylidene)-3-(2-oxo-2-phenylethyl)thiazolidine-2,4-dione (TZ4C), an inhibitor of p-Tau and memory impairment, using a SH-SY5Y cell model of methamphetamine-induced tauopathy and a scopolamine-induced memory impairment model in Wistar rats.</div><div>In the present study, the neuroprotective effect of TZ4C was studied in a SH-SY5Y cellular model of methamphetamine-induced (2 mM) tauopathy and a scopolamine-induced (1.5 mg/kg/day) memory impairment model in male Wistar rats (n = 48). The memory functions and learning abilities of the rats were evaluated using the Morris water maze (MWM) and passive avoidance tests. Additionally, AChE activity in the rat hippocampus was quantified, and the expression of p-Tau, HSP70, and caspase-3 in both <em>in vitro</em> and <em>in vivo</em> samples was evaluated through Western blot analysis.</div><div>TZ4C (0.1–1000 µM) did not exhibit significantly toxic effects on SH-SY5Y cell viability. Western blot results indicated that TZ4C led to reduced expression of p-Tau, HSP70, and cleaved caspase-3 in SH-SY5Y cells (3 and 10 µM) and the rat hippocampus (2 and 4 mg/kg). Additionally, the findings suggested that TZ4C enhanced memory function in rats with scopolamine-induced impairment and decreased acetylcholinesterase (AChE) specific activity.</div><div>The comprehensive analysis of <em>in vitro</em> and <em>in vivo</em> experiments underscores the neuroprotective potential (improved neuropathology and reduced memory impairment) of TZ4C. These findings highlight the promise of TZ4C as a candidate for drug discovery programs to identify effective therapies for AD.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"562 ","pages":"Pages 227-238"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.neuroscience.2024.10.048
Jiayu Yuan, Xiaoyu Dong, Siyu Zhou, Jianfei Nao
Alzheimer’s disease (AD) and Parkinson’s disease (PD) are neurodegenerative disorders that significantly impact well-being. Hyperoside (HYP), a flavonoid found in various plant species, particularly within the genus Hypericin, exhibits diverse pharmacological properties. However, the precise mechanisms underlying the anti-AD and anti-PD effects of HYP remain unclear. This systematic review consolidated existing preclinical research on HYP by conducting a comprehensive literature survey and analysis. The objective was to corroborate the therapeutic efficacy of HYP in AD and PD models and to synthesize its potential therapeutic mechanisms. Searches were conducted in the PubMed, CNKI, and Web of Science databases. Reliability assessment of the 17 included studies confirmed the credibility of the mechanisms of action of HYP against AD and PD. We systematically assessed the neuroprotective potential of HYP in in vivo and in vitro models of AD and PD. Our findings indicated that HYP can mitigate, intervene in, and treat AD and PD animal models and associated cells through various mechanisms, including anti-oxidative, anti-inflammatory, anti-apoptotic, anti-Aβ aggregation, and cholinesterase inhibitory activities. Therefore, HYP potentially exerts anti-AD and anti-PD effects through diverse mechanisms, making it a promising candidate for therapeutic intervention in both AD and PD.
阿尔茨海默病（AD）和帕金森病（PD）是严重影响健康的神经退行性疾病。金丝桃苷（HYP）是一种黄酮类化合物，存在于多种植物中，尤其是金丝桃苷属植物中，具有多种药理特性。然而，HYP 抗AD 和抗 PD 作用的确切机制仍不清楚。本系统综述通过进行全面的文献调查和分析，整合了现有的 HYP 临床前研究。目的是证实 HYP 在 AD 和 PD 模型中的疗效，并总结其潜在的治疗机制。研究人员在 PubMed、CNKI 和 Web of Science 数据库中进行了检索。对纳入的 17 项研究进行了可靠性评估，证实了 HYP 对 AD 和 PD 作用机制的可信性。我们系统地评估了 HYP 在体内和体外 AD 和 PD 模型中的神经保护潜力。我们的研究结果表明，HYP 可通过多种机制缓解、干预和治疗 AD 和 PD 动物模型及相关细胞，包括抗氧化、抗炎、抗凋亡、抗 Aβ 聚集和胆碱酯酶抑制活性。因此，HYP 有可能通过多种机制发挥抗 AD 和抗 PD 作用，使其成为治疗 AD 和 PD 的理想候选药物。
{"title":"Pharmacological activities and therapeutic potential of Hyperoside in the treatment of Alzheimer’s and Parkinson’s diseases: A systemic review","authors":"Jiayu Yuan, Xiaoyu Dong, Siyu Zhou, Jianfei Nao","doi":"10.1016/j.neuroscience.2024.10.048","DOIUrl":"10.1016/j.neuroscience.2024.10.048","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) and Parkinson’s disease (PD) are neurodegenerative disorders that significantly impact well-being. Hyperoside (HYP), a flavonoid found in various plant species, particularly within the genus Hypericin, exhibits diverse pharmacological properties. However, the precise mechanisms underlying the anti-AD and anti-PD effects of HYP remain unclear. This systematic review consolidated existing preclinical research on HYP by conducting a comprehensive literature survey and analysis. The objective was to corroborate the therapeutic efficacy of HYP in AD and PD models and to synthesize its potential therapeutic mechanisms. Searches were conducted in the PubMed, CNKI, and Web of Science databases. Reliability assessment of the 17 included studies confirmed the credibility of the mechanisms of action of HYP against AD and PD. We systematically assessed the neuroprotective potential of HYP in in vivo and in vitro models of AD and PD. Our findings indicated that HYP can mitigate, intervene in, and treat AD and PD animal models and associated cells through various mechanisms, including anti-oxidative, anti-inflammatory, anti-apoptotic, anti-Aβ aggregation, and cholinesterase inhibitory activities. Therefore, HYP potentially exerts anti-AD and anti-PD effects through diverse mechanisms, making it a promising candidate for therapeutic intervention in both AD and PD.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"563 ","pages":"Pages 136-147"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Depression is a complex disorder with multiple contributing factors, and chronic stress has previously been recognized as a major causative factor, while gut microbes have also been found to be involved in depression recently. However, gene expression in depression models with different etiologies is unclear. Here, we compared the transcriptomes of the striatum in chronic social defeat stress (CSDS) model of C57BL/6J male mice and fecal microbiota transplant (FMT) model of Kumming male mice. We found that the proportion of shared differentially expressed genes (DEGs) between the two models was only 24 %. The specific DEGs of FMT model were enriched in immune and inflammatory, and are associated with changes in vascular and ciliated ependymal cells. The specific DEGs of CSDS model were enriched in neuron and synapse. The results of network analysis suggested the expression patterns and biological function of depressive-like behaviors-related modules in the two models are different. Further, the alternative splicing events of CSDS are more than FMT. Our results suggested models of depression induced by different etiologies differ significantly in gene expression and biological function. Our study also suggested us to pay attention to the characteristics of models of depression of different etiologies and provided a more comprehensive understanding of the heterogeneity of depression.
{"title":"Comparative transcriptional analyses of the striatum in the chronic social defeat stress model in C57BL/6J male mice and the gut microbiota-dysbiosis model in Kumming mice","authors":"Weiyi Chen , Yiyun Liu , Juncai Pu , Siwen Gui , Dongfang Wang , Xiaogang Zhong , Wei Tao , Xiaopeng Chen , Xiang Chen , Yue Chen , Libo Zhao , Qingyuan Wu , Xiangyu Chen , Yingying Zhang , Anmu Xie , Peng Xie","doi":"10.1016/j.neuroscience.2024.10.057","DOIUrl":"10.1016/j.neuroscience.2024.10.057","url":null,"abstract":"<div><div>Depression is a complex disorder with multiple contributing factors, and chronic stress has previously been recognized as a major causative factor, while gut microbes have also been found to be involved in depression recently. However, gene expression in depression models with different etiologies is unclear. Here, we compared the transcriptomes of the striatum in chronic social defeat stress (CSDS) model of C57BL/6J male mice and fecal microbiota transplant (FMT) model of Kumming male mice. We found that the proportion of shared differentially expressed genes (DEGs) between the two models was only 24 %. The specific DEGs of FMT model were enriched in immune and inflammatory, and are associated with changes in vascular and ciliated ependymal cells. The specific DEGs of CSDS model were enriched in neuron and synapse. The results of network analysis suggested the expression patterns and biological function of depressive-like behaviors-related modules in the two models are different. Further, the alternative splicing events of CSDS are more than FMT. Our results suggested models of depression induced by different etiologies differ significantly in gene expression and biological function. Our study also suggested us to pay attention to the characteristics of models of depression of different etiologies and provided a more comprehensive understanding of the heterogeneity of depression.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"562 ","pages":"Pages 217-226"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Autism spectrum disorder (ASD) is a highly prevalent multifactorial disorder characterized by social deficits and stereotypies. Despite extensive research efforts, the etiology of ASD remains poorly understood. However, studies using preclinical models have identified the mechanistic target of rapamycin kinase (mTOR) signaling pathway as a key player in ASD-related features. This review examines genetic and environmental models of ASD, focusing on their association with the mTOR pathway. We organize findings on alterations within this pathway, providing insights about the potential mechanisms involved in the onset and maintenance of ASD symptoms. Our analysis highlights the central role of mTOR hyperactivation in disrupting autophagic processes, neural organization, and neurotransmitter pathways, which collectively contribute to ASD phenotypes. The review also discusses the therapeutic potential of mTOR pathway inhibitors, such as rapamycin, in mitigating ASD characteristics. These insights underscore the importance of the mTOR pathway as a target for future research and therapeutic intervention in ASD. This review innovates by bringing the convergence of disrupted mTOR signaling in preclinical models and clinical data associated with ASD.
{"title":"mTOR signaling pathway as a pathophysiologic mechanism in preclinical models of autism spectrum disorder","authors":"Isabela Drehmer , Júlio Santos-Terra , Carmem Gottfried , Iohanna Deckmann","doi":"10.1016/j.neuroscience.2024.10.050","DOIUrl":"10.1016/j.neuroscience.2024.10.050","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is a highly prevalent multifactorial disorder characterized by social deficits and stereotypies. Despite extensive research efforts, the etiology of ASD remains poorly understood. However, studies using preclinical models have identified the mechanistic target of rapamycin kinase (mTOR) signaling pathway as a key player in ASD-related features. This review examines genetic and environmental models of ASD, focusing on their association with the mTOR pathway. We organize findings on alterations within this pathway, providing insights about the potential mechanisms involved in the onset and maintenance of ASD symptoms. Our analysis highlights the central role of mTOR hyperactivation in disrupting autophagic processes, neural organization, and neurotransmitter pathways, which collectively contribute to ASD phenotypes. The review also discusses the therapeutic potential of mTOR pathway inhibitors, such as rapamycin, in mitigating ASD characteristics. These insights underscore the importance of the mTOR pathway as a target for future research and therapeutic intervention in ASD. This review innovates by bringing the convergence of disrupted mTOR signaling in preclinical models and clinical data associated with ASD.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"563 ","pages":"Pages 33-42"},"PeriodicalIF":2.9,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-30DOI: 10.1016/j.neuroscience.2024.10.049
Xinyu Liu , Xiaofeng Zhao , Mengsheng Qiu , Junlin Yang
Degenerative diseases and injuries of central nervous system (CNS) often cause nerve cell apoptosis and neural dysfunction. Protection of surviving cells or inducing the differentiation of stem cells into functional cells is considered to be an important way of neurorepair. In addition, transdifferentiation technology emerged recently is expected to provide new solutions for nerve regeneration. Cell surface receptors are transmembrane proteins embedded in cytoplasmic membrane, and play crucial roles in maintaining communication between extracellular signals and intracellular signaling processes. The extracellular microenvironment changed dramatically upon neural lesion, exploring the biological function of signals mediated by cell surface receptors will help to develop molecular strategies for nerve regeneration. An increasing number of studies have reported that cell surface receptor-mediated signaling affects the survival, differentiation, and functioning of neural cells, and even regulate their trans-lineage reprogramming. Here, we provide a review on the roles of cell surface receptors in CNS regeneration, thus providing new cues for better treatment of neurodegenerative diseases or nerve injury.
{"title":"Cell surface receptor-mediated signaling in CNS regeneration","authors":"Xinyu Liu , Xiaofeng Zhao , Mengsheng Qiu , Junlin Yang","doi":"10.1016/j.neuroscience.2024.10.049","DOIUrl":"10.1016/j.neuroscience.2024.10.049","url":null,"abstract":"<div><div>Degenerative diseases and injuries of central nervous system (CNS) often cause nerve cell apoptosis and neural dysfunction. Protection of surviving cells or inducing the differentiation of stem cells into functional cells is considered to be an important way of neurorepair. In addition, transdifferentiation technology emerged recently is expected to provide new solutions for nerve regeneration. Cell surface receptors are transmembrane proteins embedded in cytoplasmic membrane, and play crucial roles in maintaining communication between extracellular signals and intracellular signaling processes. The extracellular microenvironment changed dramatically upon neural lesion, exploring the biological function of signals mediated by cell surface receptors will help to develop molecular strategies for nerve regeneration. An increasing number of studies have reported that cell surface receptor-mediated signaling affects the survival, differentiation, and functioning of neural cells, and even regulate their <em>trans</em>-lineage reprogramming. Here, we provide a review on the roles of cell surface receptors in CNS regeneration, thus providing new cues for better treatment of neurodegenerative diseases or nerve injury.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"562 ","pages":"Pages 198-208"},"PeriodicalIF":2.9,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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