Pub Date : 2024-12-12DOI: 10.1016/j.brainres.2024.149389
Zekai Wan , Qiuyu Ren , Qingsong Li , Zhouyu Liu , Shuai Wang , Xiaodong Shi
Soluble β-amyloid oligomers (SAβOs) are linked to early Alzheimer’s disease (AD) cognitive decline. Our previous work identified pep63, a neuroprotective peptide composed of ten amino acids, that blocks EphB2-SAβO interaction and improves the cognitive dysfunction in an AD mouse model. In this study, we constructed fourteen truncated variants of pep63 to find the key sequences for SAβO binding. Results of the peptide array assay showed that all the N-terminal truncated variants showed a significant decrease in their abilities to bind SAβOs, indicating that the amino acids at the N-terminus are essential for pep63-SAβO interaction. However, for the C-terminal truncated variants, the deletion of the terminal one, two, or three amino acids did not affect the binding of pep63 to SAβOs. Further studies indicated that the removal of the three amino acids at the C-terminus did not affect the ability of pep63 to interfere with the EphB2-SAβO interaction in vitro. Together, these results suggest that the three amino acids at the C-terminus of pep63 are not necessary for pep63-SAβO interaction, and subsequent research could consider the therapeutic strategy using a truncated form of pep63 without the corresponding amino acids. Our data provide clues and a basis for guiding the further optimization and modification of pep63.
{"title":"The three amino acids at the C-terminus of pep63 are not necessary for its interaction with soluble Aβ oligomers","authors":"Zekai Wan , Qiuyu Ren , Qingsong Li , Zhouyu Liu , Shuai Wang , Xiaodong Shi","doi":"10.1016/j.brainres.2024.149389","DOIUrl":"10.1016/j.brainres.2024.149389","url":null,"abstract":"<div><div>Soluble β-amyloid oligomers (SAβOs) are linked to early Alzheimer’s disease (AD) cognitive decline. Our previous work identified pep63, a neuroprotective peptide composed of ten amino acids, that blocks EphB2-SAβO interaction and improves the cognitive dysfunction in an AD mouse model. In this study, we constructed fourteen truncated variants of pep63 to find the key sequences for SAβO binding. Results of the peptide array assay showed that all the N-terminal truncated variants showed a significant decrease in their abilities to bind SAβOs, indicating that the amino acids at the N-terminus are essential for pep63-SAβO interaction. However, for the C-terminal truncated variants, the deletion of the terminal one, two, or three amino acids did not affect the binding of pep63 to SAβOs. Further studies indicated that the removal of the three amino acids at the C-terminus did not affect the ability of pep63 to interfere with the EphB2-SAβO interaction <em>in vitro</em>. Together, these results suggest that the three amino acids at the C-terminus of pep63 are not necessary for pep63-SAβO interaction, and subsequent research could consider the therapeutic strategy using a truncated form of pep63 without the corresponding amino acids. Our data provide clues and a basis for guiding the further optimization and modification of pep63.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149389"},"PeriodicalIF":2.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143131407","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 : 2024-12-12DOI: 10.1016/j.brainres.2024.149401
Hui Li , Linghui Dong , Jiajie Liu , Xiaonian Zhang , Hao Zhang
Aims
To explore the functional brain imaging characteristics of patients with disorders of consciousness (DoC).
Methods
This prospective cohort study consecutively enrolled 27 patients in minimally conscious state (MCS), 23 in vegetative state (VS), and 25 age-matched healthy controls (HC). Resting-state functional magnetic resonance imaging (rs-fMRI) was employed to evaluate the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), degree centrality (DC), and functional connectivity (FC). Sliding windows approach was conducted to construct dynamic FC (dFC) matrices. Moreover, receiver operating characteristic analysis and Pearson correlation were used to distinguish these altered characteristics in DoC.
Results
Both MCS and VS exhibited lower ALFF, ReHo, and DC values, along with reduced FC in multiple brain regions compared with HC. Furthermore, the values in certain regions of VS were lower than those in MCS. The primary differences in brain function between patients with varying levels of consciousness were evident in the cortico-striatopallidal-thalamo-cortical mesocircuit. Significant differences in the temporal properties of dFC (including frequency, mean dwell time, number of transitions, and transition probability) were also noted among the three groups. Moreover, these multimodal alterations demonstrated high classificatory accuracy (AUC > 0.8) and were correlated with the Coma Recovery Scale-Revised (CRS-R).
Conclusion
Patients with DoC displayed abnormal patterns in local and global dynamic and static brain functions. These alterations in rs-fMRI were closely related to the level of consciousness.
{"title":"Abnormal characteristics in disorders of consciousness: A resting-state functional magnetic resonance imaging study","authors":"Hui Li , Linghui Dong , Jiajie Liu , Xiaonian Zhang , Hao Zhang","doi":"10.1016/j.brainres.2024.149401","DOIUrl":"10.1016/j.brainres.2024.149401","url":null,"abstract":"<div><h3>Aims</h3><div>To explore the functional brain imaging characteristics of patients with disorders of consciousness (DoC).</div></div><div><h3>Methods</h3><div>This prospective cohort study consecutively enrolled 27 patients in minimally conscious state (MCS), 23 in vegetative state (VS), and 25 age-matched healthy controls (HC). Resting-state functional magnetic resonance imaging (rs-fMRI) was employed to evaluate the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), degree centrality (DC), and functional connectivity (FC). Sliding windows approach was conducted to construct dynamic FC (dFC) matrices. Moreover, receiver operating characteristic analysis and Pearson correlation were used to distinguish these altered characteristics in DoC.</div></div><div><h3>Results</h3><div>Both MCS and VS exhibited lower ALFF, ReHo, and DC values, along with reduced FC in multiple brain regions compared with HC. Furthermore, the values in certain regions of VS were lower than those in MCS. The primary differences in brain function between patients with varying levels of consciousness were evident in the cortico-striatopallidal-thalamo-cortical mesocircuit. Significant differences in the temporal properties of dFC (including frequency, mean dwell time, number of transitions, and transition probability) were also noted among the three groups. Moreover, these multimodal alterations demonstrated high classificatory accuracy (AUC > 0.8) and were correlated with the Coma Recovery Scale-Revised (CRS-R).</div></div><div><h3>Conclusion</h3><div>Patients with DoC displayed abnormal patterns in local and global dynamic and static brain functions. These alterations in rs-fMRI were closely related to the level of consciousness.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149401"},"PeriodicalIF":2.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823874","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 : 2024-12-11DOI: 10.1016/j.brainres.2024.149393
Ricardo Augusto Leoni De Sousa , Bruno Ferreira Mendes
Cell-based treatment has experienced exponential expansion in recent years in terms of clinical application and market share among pharmaceutical companies. When malignant cells in a healthy individual produce antigenic peptides derived from mutant or improperly synthesized proteins, the immune system attacks and kills the transforming cells. This process is carried out continuously by immune cells scanning the body for altered cells that could cause some harm. T-regulatory cells (Tregs), which preserve immunological tolerance and can exert neuroprotective benefits in numerous disorders, including animal models of Alzheimer’s disease (AD), have demonstrated considerable therapeutic potential. Evidence also suggests that not only Tregs, but extracellular vesicles (EVs) are involved in a wide range of diseases, such as cellular homoeostasis, infection propagation, cancer development and heart disease, and have become a promisor cell-based therapeutic field too. Nevertheless, despite significant recent clinical and commercial breakthroughs, cell-based medicines still confront numerous challenges that hinder their general translation and commercialization. These challenges include, but are not limited to, choosing the best cell source, and creating a product that is safe, adequately viable, and fits the needs of individual patients and diseases. Here, we summarize what we know about Tregs and EVs and their potential therapeutic usage in AD.
{"title":"T-regulatory cells and extracellular vesicles in Alzheimer’s disease: New therapeutic concepts and hypotheses","authors":"Ricardo Augusto Leoni De Sousa , Bruno Ferreira Mendes","doi":"10.1016/j.brainres.2024.149393","DOIUrl":"10.1016/j.brainres.2024.149393","url":null,"abstract":"<div><div>Cell-based treatment has experienced exponential expansion in recent years in terms of clinical application and market share among pharmaceutical companies. When malignant cells in a healthy individual produce antigenic peptides derived from mutant or improperly synthesized proteins, the immune system attacks and kills the transforming cells. This process is carried out continuously by immune cells scanning the body for altered cells that could cause some harm. T-regulatory cells (Tregs), which preserve immunological tolerance and can exert neuroprotective benefits in numerous disorders, including animal models of Alzheimer’s disease (AD), have demonstrated considerable therapeutic potential. Evidence also suggests that not only Tregs, but extracellular vesicles (EVs) are involved in a wide range of diseases, such as cellular homoeostasis, infection propagation, cancer development and heart disease, and have become a promisor cell-based therapeutic field too. Nevertheless, despite significant recent clinical and commercial breakthroughs, cell-based medicines still confront numerous challenges that hinder their general translation and commercialization. These challenges include, but are not limited to, choosing the best cell source, and creating a product that is safe, adequately viable, and fits the needs of individual patients and diseases. Here, we summarize what we know about Tregs and EVs and their potential therapeutic usage in AD.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149393"},"PeriodicalIF":2.7,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821805","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}
Notch signaling, a classical signaling pathway of neurogenesis, is downregulated during the aging and age-related neurodegenerative diseases. Exercise has been proposed as an effective lifestyle intervention for delaying cognitive decline. However, it remains unclear whether exercise intervention could alleviate cognitive decline by modulating neurogenesis in naturally aging rats. In this study, 21-month-old natural aging rats were used to study brain aging. The natural aging rats underwent different forms of exercise training (aerobic exercise or strength training or comprehensive exercise with aerobic exercise and strength training) for 12 consecutive weeks. The cognitive function of natural aging rats was determined by Morris Water Maze. Notch signaling, autophagy-related proteins and hippocampal neurogenesis were examined by immunofluorescence, qRT-PCR and Western blot. Results showed that natural aging rats exhibited cognitive decline, accumulation of AD pathological proteins (APP and Aβ), and decreased neurogenesis (decreased DCX, Ki67 and GFAP), compared with the young control rats. Moreover, a significant decline in Notch signaling and autophagy was found in the hippocampus of natural aging rats. However, different forms of exercise upregulated Notch signaling and its downstream target genes, as well as autophagy-related proteins, including LC3, Beclin1, and p62. In summary, our data suggest that different forms of exercise can mitigate brain aging by upregulating Notch signaling and autophagy, thereby increasing hippocampal neurogenesis and improves spatial learning and memory abilities.
{"title":"Exercise alleviates cognitive decline of natural aging rats by upregulating Notch-mediated autophagy signaling","authors":"Dandan Chen , Yuan Guo , Meng Zhang , Xingran Liu , Baowen Zhang , Xianjuan Kou","doi":"10.1016/j.brainres.2024.149398","DOIUrl":"10.1016/j.brainres.2024.149398","url":null,"abstract":"<div><div>Notch signaling, a classical signaling pathway of neurogenesis, is downregulated during the aging and age-related neurodegenerative diseases. Exercise has been proposed as an effective lifestyle intervention for delaying cognitive decline. However, it remains unclear whether exercise intervention could alleviate cognitive decline by modulating neurogenesis in naturally aging rats. In this study, 21-month-old natural aging rats were used to study brain aging. The natural aging rats underwent different forms of exercise training (aerobic exercise or strength training or comprehensive exercise with aerobic exercise and strength training) for 12 consecutive weeks. The cognitive function of natural aging rats was determined by Morris Water Maze. Notch signaling, autophagy-related proteins and hippocampal neurogenesis were examined by immunofluorescence, qRT-PCR and Western blot. Results showed that natural aging rats exhibited cognitive decline, accumulation of AD pathological proteins (APP and Aβ), and decreased neurogenesis (decreased DCX, Ki67 and GFAP), compared with the young control rats. Moreover, a significant decline in Notch signaling and autophagy was found in the hippocampus of natural aging rats. However, different forms of exercise upregulated Notch signaling and its downstream target genes, as well as autophagy-related proteins, including LC3, Beclin1, and p62. In summary, our data suggest that different forms of exercise can mitigate brain aging by upregulating Notch signaling and autophagy, thereby increasing hippocampal neurogenesis and improves spatial learning and memory abilities.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149398"},"PeriodicalIF":2.7,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817252","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 : 2024-12-10DOI: 10.1016/j.brainres.2024.149397
Baoquan Wen , Xiuzhi Li , Jiafu Xu , Yuqin He , Xiaofeng Lin , Xiujuan Wu , Chaoyin Wu
Parkinson’s disease (PD) is the second most common neurodegenerative disease, but treatment options for PD are limited, and drug development has reached a bottleneck. With the progress of the aging population, the number of PD patients in China is increasing day by day, imposing a heavy burden on patients and society. Therefore, it is urgent to explore targeted medicine based on the pathogenesis of PD and disease targets. Ancient physicians have used the traditional Chinese medicine formula SiJunZi decoction (SJZD) to treat PD. However, it is less commonly used clinically now, and its pharmacological mechanism still needs to be further elucidated. In this study, based on network pharmacology research and molecular docking technology, the mechanism of SJZD in treating PD was revealed, showing that the extract of SJZD acts on cell microdomain membranes and lipid rafts, affecting ubiquitin-protein ligase binding and ubiquitin-like protein ligase binding processes, and plays a role in neurogenesis. Molecular docking results showed that Ellipticine and Hederagenin in SJZD exhibited significant effects on targets: CASP3, BCL2, and PTGS2. The effect of SJZD reversing MPP+-induced SH-SY5Y cells injury was verified by experiments, concentrations ranging from 5ug/mL to 0.1ug/mL showed significant cell protection at 24 h.
{"title":"The mechanism of SiJunZi decoction in the treatment of Parkinson’s disease","authors":"Baoquan Wen , Xiuzhi Li , Jiafu Xu , Yuqin He , Xiaofeng Lin , Xiujuan Wu , Chaoyin Wu","doi":"10.1016/j.brainres.2024.149397","DOIUrl":"10.1016/j.brainres.2024.149397","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is the second most common neurodegenerative disease, but treatment options for PD are limited, and drug development has reached a bottleneck. With the progress of the aging population, the number of PD patients in China is increasing day by day, imposing a heavy burden on patients and society. Therefore, it is urgent to explore targeted medicine based on the pathogenesis of PD and disease targets. Ancient physicians have used the traditional Chinese medicine formula SiJunZi decoction (SJZD) to treat PD. However, it is less commonly used clinically now, and its pharmacological mechanism still needs to be further elucidated. In this study, based on network pharmacology research and molecular docking technology, the mechanism of SJZD in treating PD was revealed, showing that the extract of SJZD acts on cell microdomain membranes and lipid rafts, affecting ubiquitin-protein ligase binding and ubiquitin-like protein ligase binding processes, and plays a role in neurogenesis. Molecular docking results showed that Ellipticine and Hederagenin in SJZD exhibited significant effects on targets: <em>CASP3, BCL2</em>, and <em>PTGS2.</em> The effect of SJZD reversing MPP<sup>+</sup>-induced SH-SY5Y cells injury was verified by experiments, concentrations ranging from 5ug/mL to 0.1ug/mL showed significant cell protection at 24 h.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149397"},"PeriodicalIF":2.7,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817035","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 : 2024-12-10DOI: 10.1016/j.brainres.2024.149399
Adele E. Cave , Frances M. De Blasio , Dennis H. Chang , Gerald W. Münch , Genevieve Z. Steiner-Lim
Subjective Cognitive Impairment (SCI) is a self-perceived worsening of cognitive decline, carrying an increased risk of developing Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD). Due to the self-report nature of SCI, an understanding of the biological mechanisms that contribute to an increased dementia risk is needed. This study aims to assess the differences in resting state electroencephalography (EEG) (eyes-open, eyes-closed; EO, EC) between older adults with SCI and healthy controls (HCs) utilising frequency principal components analysis (fPCA), a novel data driven approach. Participants (n = 14 per group: SCI, HCs) were matched on age, sex, years of education, mood, cognition, and pre-morbid function. Continuous resting EEG was recorded during 2-minute conditions (EO, EC) and were submitted to 4 separate fPCAs (each condition, group). Corresponding components were assessed between groups and conditions, correlated with demographics, mood, and cognition variables; multivariate logistic regression was also carried out. Component amplitudes were larger in HCs for delta-theta and alpha–beta, while theta-alpha was larger for SCI. DASS anxiety scores contributed to higher amplitudes for HCs in EO delta-theta and alpha–beta, while male sex and depressive symptoms contributed to higher amplitudes for the SCI group in EO and EC theta-alpha. Findings demonstrate a distinct divergent signature of neurological activity in older people with SCI, despite normal objective cognitive function. This is the first fPCA study to investigate neuronal differences between HCs and older adults with SCI at rest. Novel confounders and effect modifiers were identified that should be controlled in future studies.
{"title":"Eyes-open and eyes-closed EEG of older adults with subjective cognitive impairment versus healthy controls: A frequency principal components analysis study","authors":"Adele E. Cave , Frances M. De Blasio , Dennis H. Chang , Gerald W. Münch , Genevieve Z. Steiner-Lim","doi":"10.1016/j.brainres.2024.149399","DOIUrl":"10.1016/j.brainres.2024.149399","url":null,"abstract":"<div><div>Subjective Cognitive Impairment (SCI) is a self-perceived worsening of cognitive decline, carrying an increased risk of developing Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD). Due to the self-report nature of SCI, an understanding of the biological mechanisms that contribute to an increased dementia risk is needed. This study aims to assess the differences in resting state electroencephalography (EEG) (eyes-open, eyes-closed; EO, EC) between older adults with SCI and healthy controls (HCs) utilising frequency principal components analysis (fPCA), a novel data driven approach. Participants (<em>n</em> = 14 per group: SCI, HCs) were matched on age, sex, years of education, mood, cognition, and pre-morbid function. Continuous resting EEG was recorded during 2-minute conditions (EO, EC) and were submitted to 4 separate fPCAs (each condition, group). Corresponding components were assessed between groups and conditions, correlated with demographics, mood, and cognition variables; multivariate logistic regression was also carried out. Component amplitudes were larger in HCs for delta-theta and alpha–beta, while theta-alpha was larger for SCI. DASS anxiety scores contributed to higher amplitudes for HCs in EO delta-theta and alpha–beta, while male sex and depressive symptoms contributed to higher amplitudes for the SCI group in EO and EC theta-alpha. Findings demonstrate a distinct divergent signature of neurological activity in older people with SCI, despite normal objective cognitive function. This is the first fPCA study to investigate neuronal differences between HCs and older adults with SCI at rest. Novel confounders and effect modifiers were identified that should be controlled in future studies.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149399"},"PeriodicalIF":2.7,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817255","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 : 2024-12-09DOI: 10.1016/j.brainres.2024.149392
Huan Yang , Jie Gao , Hai-Yan Wang , Xin-Mei Ma , Bing-Yao Liu , Qian-Zhong Song , Hui Cheng , Sen Li , Zai-Yun Long , Xiu-Min Lu , Yong-Tang Wang
Whole-body vibration (WBV) is a physical stimulation method that transmits mechanical oscillations to the entire body through a vibration platform or device. Biokinetic and epidemiologic studies have shown that prolonged exposure to high-intensity WBV increases health risks, primarily to the lumbar spine and the nervous system connected to it. There is currently insufficient evidence to demonstrate a quantitative relationship between vibration exposure and risk of health effects. The positive effects of WBV on increasing muscle strength and improving balance and flexibility are well known, but its effects on cognitive function are more complex, with mixed findings, largely related to vibration conditions, including frequency, amplitude, and duration. Studies have shown that short-term low-frequency WBV may have a positive impact on cognitive function, demonstrates potential rehabilitation benefits in enhancing learning and memory, possibly by promoting neuromuscular coordination and enhancing neural plasticity. However, long term exposure to vibration may lead to chronic stress in nerve tissue, affecting nerve conduction efficiency and potentially interfering with neuroprotective mechanisms, thereby having a negative impact on cognitive ability, even causes symptoms such as cognitive decline, mental fatigue, decreased attention, and drowsiness. This literature review aimed to explore the effects of WBV on cognitive function and further to analyze the possible mechanisms. Based on the analysis of literatures, we came to the conclusion that the impact of WBV on cognitive function depends mainly on the frequency and duration of vibration, short-term low-frequency WBV may have a positive impact on cognitive function, while long term exposure to WBV may lead to cognitive decline, and the mechanisms may be involved in neuroinflammation, oxidative stress, synaptic plasticity, and neurotransmitter changes. This review may provide some theoretical foundations and guidance for the prevention and treatment of WBV induced cognitive impairment.
{"title":"The effects and possible mechanisms of whole-body vibration on cognitive function: A narrative review","authors":"Huan Yang , Jie Gao , Hai-Yan Wang , Xin-Mei Ma , Bing-Yao Liu , Qian-Zhong Song , Hui Cheng , Sen Li , Zai-Yun Long , Xiu-Min Lu , Yong-Tang Wang","doi":"10.1016/j.brainres.2024.149392","DOIUrl":"10.1016/j.brainres.2024.149392","url":null,"abstract":"<div><div>Whole-body vibration (WBV) is a physical stimulation method that transmits mechanical oscillations to the entire body through a vibration platform or device. Biokinetic and epidemiologic studies have shown that prolonged exposure to high-intensity WBV increases health risks, primarily to the lumbar spine and the nervous system connected to it. There is currently insufficient evidence to demonstrate a quantitative relationship between vibration exposure and risk of health effects. The positive effects of WBV on increasing muscle strength and improving balance and flexibility are well known, but its effects on cognitive function are more complex, with mixed findings, largely related to vibration conditions, including frequency, amplitude, and duration. Studies have shown that short-term low-frequency WBV may have a positive impact on cognitive function, demonstrates potential rehabilitation benefits in enhancing learning and memory, possibly by promoting neuromuscular coordination and enhancing neural plasticity. However, long term exposure to vibration may lead to chronic stress in nerve tissue, affecting nerve conduction efficiency and potentially interfering with neuroprotective mechanisms, thereby having a negative impact on cognitive ability, even causes symptoms such as cognitive decline, mental fatigue, decreased attention, and drowsiness. This literature review aimed to explore the effects of WBV on cognitive function and further to analyze the possible mechanisms. Based on the analysis of literatures, we came to the conclusion that the impact of WBV on cognitive function depends mainly on the frequency and duration of vibration, short-term low-frequency WBV may have a positive impact on cognitive function, while long term exposure to WBV may lead to cognitive decline, and the mechanisms may be involved in neuroinflammation, oxidative stress, synaptic plasticity, and neurotransmitter changes. This review may provide some theoretical foundations and guidance for the prevention and treatment of WBV induced cognitive impairment.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149392"},"PeriodicalIF":2.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812169","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 : 2024-12-09DOI: 10.1016/j.brainres.2024.149395
Zhongqian Su , Yuxiang Li , Fangchao Tong , Yiying Cai , Yuanfang Li , Jing Ding , Qiang Wang , Xin Wang
Objective
Our study aimed to investigate the role of CRMP2 in mossy fiber sprouting (MFS) using a pilocarpine-induced rat model of epilepsy.
Methods
First, the rats were sacrificed on the 1, 7, 14 and 28 day after pilocarpine injection. Quantitative Real-time PCR (qPCR) and Western blot (WB) were performed to assess mRNA and protein levels in the hippocampus and cortex. Next, shCRMP2 AAV was injected into the dentate gyrus of hippocampus to knock down CRMP2 expression. Two weeks later, the epileptic rat model was induced by pilocarpine injection. On the day of status epilepticus (SE) induction, animals in the shCtrl + EP + LCM and shCRMP2 + EP + LCM group received twice-daily intragastric administration of Lacosamide (LCM). The rats were video monitored from day 7 to 28, and were sacrificed on day 28 after pilocarpine injection for subsequent experiment.
Results
In the present study, we observed downregulation of phosphorylated CRMP2 in the hippocampus of epileptic rats. Additionally, LCM treatment reduces the expression level of CRMP2 protein in the hippocampus of these rats. Both CRMP2 knockdown and LCM treatment were found to decrease mossy fiber sprouting (MFS) in the dentate gyrus and shorten the duration of seizures in epileptic rats. Furthermore, we discovered that microtubule dynamics are reduced in the hippocampus of epileptic rats. Both CRMP2 Knockdown and LCM treatment were shown to increase the microtubule dynamics in the hippocampus of rats with epilepsy.
Conclusion
In conclusion, we demonstrated convincingly that CRMP2 regulates mossy fiber sprouting and modulates microtubule dynamics in a pilocarpine induced rat model of epilepsy.
目的：通过匹罗卡品诱导的大鼠癫痫模型，探讨CRMP2在苔藓纤维发芽（MFS）中的作用。方法：首先在注射匹罗卡品后1、7、14、28 d处死大鼠。采用实时荧光定量PCR （qPCR）和Western blot （WB）检测海马和皮层mRNA和蛋白水平。接下来，将shCRMP2 AAV注入海马齿状回，以降低CRMP2的表达。2周后，注射匹罗卡品致痫大鼠模型。在癫痫持续状态（SE）诱导当天，shCtrl + EP + LCM组和shCRMP2 + EP + LCM组动物每天2次灌胃拉科沙胺（LCM）。第7 ~ 28天对大鼠进行视频监测，注射匹罗卡品后第28天处死，进行后续实验。结果：在本研究中，我们观察到癫痫大鼠海马中磷酸化的CRMP2下调。此外，LCM处理降低了这些大鼠海马中CRMP2蛋白的表达水平。CRMP2敲除和LCM治疗均可降低癫痫大鼠齿状回苔藓纤维发芽（MFS），缩短癫痫发作持续时间。此外，我们发现癫痫大鼠海马的微管动力学降低。CRMP2敲除和LCM治疗均可增加癫痫大鼠海马的微管动力学。结论：在匹罗卡品诱导的大鼠癫痫模型中，我们令人信服地证明了CRMP2调节苔藓纤维发芽和调节微管动力学。
{"title":"CRMP2 regulates mossy fiber sprouting and modulates microtubule dynamics in a pilocarpine induced rat model of epilepsy","authors":"Zhongqian Su , Yuxiang Li , Fangchao Tong , Yiying Cai , Yuanfang Li , Jing Ding , Qiang Wang , Xin Wang","doi":"10.1016/j.brainres.2024.149395","DOIUrl":"10.1016/j.brainres.2024.149395","url":null,"abstract":"<div><h3>Objective</h3><div>Our study aimed to investigate the role of CRMP2 in mossy fiber sprouting (MFS) using a pilocarpine-induced rat model of epilepsy.</div></div><div><h3>Methods</h3><div>First, the rats were sacrificed on the 1, 7, 14 and 28 day after pilocarpine injection. Quantitative Real-time PCR (qPCR) and Western blot (WB) were performed to assess mRNA and protein levels in the hippocampus and cortex. Next, shCRMP2 AAV was injected into the dentate gyrus of hippocampus to knock down CRMP2 expression. Two weeks later, the epileptic rat model was induced by pilocarpine injection. On the day of status epilepticus (SE) induction, animals in the shCtrl + EP + LCM and shCRMP2 + EP + LCM group received twice-daily intragastric administration of Lacosamide (LCM). The rats were video monitored from day 7 to 28, and were sacrificed on day 28 after pilocarpine injection for subsequent experiment.</div></div><div><h3>Results</h3><div>In the present study, we observed downregulation of phosphorylated CRMP2 in the hippocampus of epileptic rats. Additionally, LCM treatment reduces the expression level of CRMP2 protein in the hippocampus of these rats. Both CRMP2 knockdown and LCM treatment were found to decrease mossy fiber sprouting (MFS) in the dentate gyrus and shorten the duration of seizures in epileptic rats. Furthermore, we discovered that microtubule dynamics are reduced in the hippocampus of epileptic rats. Both CRMP2 Knockdown and LCM treatment were shown to increase the microtubule dynamics in the hippocampus of rats with epilepsy.</div></div><div><h3>Conclusion</h3><div>In conclusion, we demonstrated convincingly that CRMP2 regulates mossy fiber sprouting and modulates microtubule dynamics in a pilocarpine induced rat model of epilepsy.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149395"},"PeriodicalIF":2.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812166","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 : 2024-12-09DOI: 10.1016/j.brainres.2024.149396
Shan Liu , Zhenfeng Fan , Minke FU , Keling Cheng , Xin Zhang , Jun Ni , ZhiYong Wang
Objective
To investigate the impact of inspiratory muscle training on lung function and swallowing function in patients with dysphagia-induced aspiration following ischemic stroke and to evaluate the effectiveness of inspiratory muscle training on aspiration symptoms.
Methods
Fifty-eight inpatients with dysphagia-induced aspiration following ischemic stroke were selected and randomly divided into a control group (n = 29, conventional swallowing therapy) and a treatment group (n = 29, conventional swallowing therapy plus inspiratory muscle training). Both groups received conventional swallowing function training, including oral sensory training, oral motor training, airway safety protection training, and neuromuscular electrical stimulation therapy for 10–20 min per session, twice daily for 2 weeks. The treatment group additionally received inspiratory muscle resistance training using the POWERbreathe device for 20 min per session, twice daily for 2 weeks. Swallowing function was assessed using the Penetration–Aspiration Scale (PAS), Functional Dysphagia Scale (FDS), and Functional Oral Intake Scale (FOIS) based on the videofluoroscopic swallowing study (VFSS) before and after treatment. Lung function, including maximal peak expiratory flow rate (PEF) and forced vital capacity (FVC), was evaluated using the Miraclink X-SCRIBE cardiac stress testing system.
Results
Before treatment, there were no significant differences in FOIS, FDS, and PAS scores between the two groups (P > 0.05), while post-treatment, both groups showed significant improvements in these indicators (P < 0.05), with the treatment group showing more significant improvements than the control group (P < 0.05). Further, before treatment, there were no significant differences in FVC and PEF scores between the two groups (P > 0.05), whereas post-treatment, the treatment group showed significant improvements in these indicators (P < 0.05) and the control group showed no significant changes (P > 0.05). The treatment group also showed more significant improvements than the control group (P < 0.05). Finally, a correlation analysis revealed a significant linear relationship between FVC and PEF in the post-treatment PAS in the treatment group (P < 0.05).
Conclusion
Inspiratory muscle training can improve lung function in patients with dysphagia following ischemic stroke, as it develops swallowing function more effectively than conventional swallowing function training alone. Moreover, inspiratory muscle training is effective in treating aspiration caused by dysphagia, with enhancements in aspiration related to improved lung function.
{"title":"Impact of inspiratory muscle training on aspiration symptoms in patients with dysphagia following ischemic stroke","authors":"Shan Liu , Zhenfeng Fan , Minke FU , Keling Cheng , Xin Zhang , Jun Ni , ZhiYong Wang","doi":"10.1016/j.brainres.2024.149396","DOIUrl":"10.1016/j.brainres.2024.149396","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the impact of inspiratory muscle training on lung function and swallowing function in patients with dysphagia-induced aspiration following ischemic stroke and to evaluate the effectiveness of inspiratory muscle training on aspiration symptoms.</div></div><div><h3>Methods</h3><div>Fifty-eight inpatients with dysphagia-induced aspiration following ischemic stroke were selected and randomly divided into a control group (n = 29, conventional swallowing therapy) and a treatment group (n = 29, conventional swallowing therapy plus inspiratory muscle training). Both groups received conventional swallowing function training, including oral sensory training, oral motor training, airway safety protection training, and neuromuscular electrical stimulation therapy for 10–20 min per session, twice daily for 2 weeks. The treatment group additionally received inspiratory muscle resistance training using the POWERbreathe device for 20 min per session, twice daily for 2 weeks. Swallowing function was assessed using the Penetration–Aspiration Scale (PAS), Functional Dysphagia Scale (FDS), and Functional Oral Intake Scale (FOIS) based on the videofluoroscopic swallowing study (VFSS) before and after treatment. Lung function, including maximal peak expiratory flow rate (PEF) and forced vital capacity (FVC), was evaluated using the Miraclink X-SCRIBE cardiac stress testing system.</div></div><div><h3>Results</h3><div>Before treatment, there were no significant differences in FOIS, FDS, and PAS scores between the two groups (P > 0.05), while post-treatment, both groups showed significant improvements in these indicators (P < 0.05), with the treatment group showing more significant improvements than the control group (P < 0.05). Further, before treatment, there were no significant differences in FVC and PEF scores between the two groups (P > 0.05), whereas post-treatment, the treatment group showed significant improvements in these indicators (P < 0.05) and the control group showed no significant changes (P > 0.05). The treatment group also showed more significant improvements than the control group (P < 0.05). Finally, a correlation analysis revealed a significant linear relationship between FVC and PEF in the post-treatment PAS in the treatment group (P < 0.05).</div></div><div><h3>Conclusion</h3><div>Inspiratory muscle training can improve lung function in patients with dysphagia following ischemic stroke, as it develops swallowing function more effectively than conventional swallowing function training alone. Moreover, inspiratory muscle training is effective in treating aspiration caused by dysphagia, with enhancements in aspiration related to improved lung function.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1850 ","pages":"Article 149396"},"PeriodicalIF":2.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812168","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}
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