Tourette syndrome (TS) is a neurodevelopmental disorder characterized by impaired or delayed functional development. Although the pathology of TS remains to be determined, the continuous development of science and technology has provided new perspectives to understand its pathological mechanism. Research into non-invasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation and direct current stimulation, have shown promising therapeutic potential in clinical studies. Furthermore, NIBS has been shown to affect the brain of patients with TS, including synaptic transmission, release of neurotransmitters, in addition to the activation of microglial cells and astrocytes. However, an exploration of the innate mechanisms is still lacking. This review aims to summarize the pathogenesis of TS and intervention with NIBS in clinical patients with TS. It aims to provide a theoretical basis for more in-depth investigations of innovative therapies for TS in the future.
{"title":"Role and related mechanisms of non-invasive brain stimulation in the treatment of Tourette syndrome","authors":"Boshen Liang , Yang Zhou , Chengting Jiang , Ting Zhao , Dongdong Qin , Fabao Gao","doi":"10.1016/j.brainresbull.2025.111258","DOIUrl":"10.1016/j.brainresbull.2025.111258","url":null,"abstract":"<div><div>Tourette syndrome (TS) is a neurodevelopmental disorder characterized by impaired or delayed functional development. Although the pathology of TS remains to be determined, the continuous development of science and technology has provided new perspectives to understand its pathological mechanism. Research into non-invasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation and direct current stimulation, have shown promising therapeutic potential in clinical studies. Furthermore, NIBS has been shown to affect the brain of patients with TS, including synaptic transmission, release of neurotransmitters, in addition to the activation of microglial cells and astrocytes. However, an exploration of the innate mechanisms is still lacking. This review aims to summarize the pathogenesis of TS and intervention with NIBS in clinical patients with TS. It aims to provide a theoretical basis for more in-depth investigations of innovative therapies for TS in the future.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111258"},"PeriodicalIF":3.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-12DOI: 10.1016/j.brainresbull.2025.111257
Ana P.A. Dagnino , Gabriel Rübensam , Jefferson B. Silva , Maria M. Campos
Background
The treatment of fibromyalgia remains a current challenge. While the analgesic effects of mesenchymal stem cells have been the subject of previous research, their potential in managing fibromyalgia symptoms needs further investigation. In this study, we investigated the effects of human stem cells from tooth apical papilla (SCAP), when administered systemically, in a mouse model of fibromyalgia induced by reserpine.
Methods
The effects of repeated intraperitoneal (i.p.) treatment with SCAP were evaluated in the mouse model of fibromyalgia induced by reserpine, by assessing behavioral and biochemical parameters.
Results
The systemic treatment with SCAP significantly reduced the mechanical and thermal hypersensitivity induced by reserpine in mice. Moreover, the SCAP treatment also reversed depression-like behavior, as assessed in the forced swimming test (FST). The SCAP administration partly restored the reduction in the total number of entries in the elevated plus maze but failed to alter the fatigue intensity or the grip strength. The treatment with SCAP significantly increased dopamine, glutamate, and glutathione levels in the masseter muscle compared to the vehicle-treated control animals. Conversely, the SCAP administration decreased the glutathione levels in the prefrontal cortex and spinal cord compared to the control mice. Finally, the repeated treatment with SCAP led to a significant increase in the spinal cord levels of the chemokine CXCL1/KC.
Conclusions
Our research findings offer new insights into the efficacy of human SCAP in a pre-clinical model of fibromyalgia, likely through the modulation of both peripheral and central mechanisms.
{"title":"Stem cells from tooth apical papilla modulate fibromyalgia-like changes in mice","authors":"Ana P.A. Dagnino , Gabriel Rübensam , Jefferson B. Silva , Maria M. Campos","doi":"10.1016/j.brainresbull.2025.111257","DOIUrl":"10.1016/j.brainresbull.2025.111257","url":null,"abstract":"<div><h3>Background</h3><div>The treatment of fibromyalgia remains a current challenge. While the analgesic effects of mesenchymal stem cells have been the subject of previous research, their potential in managing fibromyalgia symptoms needs further investigation. In this study, we investigated the effects of human stem cells from tooth apical papilla (SCAP), when administered systemically, in a mouse model of fibromyalgia induced by reserpine.</div></div><div><h3>Methods</h3><div>The effects of repeated intraperitoneal (i.p.) treatment with SCAP were evaluated in the mouse model of fibromyalgia induced by reserpine, by assessing behavioral and biochemical parameters.</div></div><div><h3>Results</h3><div>The systemic treatment with SCAP significantly reduced the mechanical and thermal hypersensitivity induced by reserpine in mice. Moreover, the SCAP treatment also reversed depression-like behavior, as assessed in the forced swimming test (FST). The SCAP administration partly restored the reduction in the total number of entries in the elevated plus maze but failed to alter the fatigue intensity or the grip strength. The treatment with SCAP significantly increased dopamine, glutamate, and glutathione levels in the masseter muscle compared to the vehicle-treated control animals. Conversely, the SCAP administration decreased the glutathione levels in the prefrontal cortex and spinal cord compared to the control mice. Finally, the repeated treatment with SCAP led to a significant increase in the spinal cord levels of the chemokine CXCL1/KC.</div></div><div><h3>Conclusions</h3><div>Our research findings offer new insights into the efficacy of human SCAP in a pre-clinical model of fibromyalgia, likely through the modulation of both peripheral and central mechanisms.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111257"},"PeriodicalIF":3.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Multiple sclerosis (MS) is a chronic autoimmune illness characterized by inflammation and demyelination of the central nervous system (CNS). The effective delivery of therapeutic agents to the CNS continues to be an important barrier in MS treatment due to the blood-brain barrier and limited access to the affected areas. Exosome-based drug delivery systems have become an attractive option for targeted therapy in MS. Exosomes, small extracellular vesicles derived from various cell types, possess unique biological properties that make them ideal nanocarriers for delivering therapeutic cargo to specific cell populations in the CNS. In this study, we supply a comprehensive overview of the current advances and future perspectives of exosome-based drug delivery systems for MS. We discuss the biogenesis of exosomes, strategies for cargo loading, engineering approaches to enhance their targeting capabilities, and the potential clinical applications of exosome-mediated drug delivery in MS therapy. Additionally, we explore preclinical studies and animal models that demonstrate the effectiveness of exosome-based drug delivery in ameliorating MS pathology. By highlighting the challenges and opportunities in utilizing exosomes as drug delivery vehicles, this review aims to contribute to the growing body of knowledge in the field of nanomedicine for MS. Considering the potential of exosome-based drug delivery systems to enhance the accessibility, specificity, and effectiveness of therapies while minimizing off-target effects might change the therapeutic scenario for MS.
{"title":"Exosome-based platforms for treatment of multiple sclerosis","authors":"Aidin Mohammadi Zonouz , Mahboobeh Ghasemzadeh Rahbardar , Mona Alibolandi","doi":"10.1016/j.brainresbull.2025.111256","DOIUrl":"10.1016/j.brainresbull.2025.111256","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a chronic autoimmune illness characterized by inflammation and demyelination of the central nervous system (CNS). The effective delivery of therapeutic agents to the CNS continues to be an important barrier in MS treatment due to the blood-brain barrier and limited access to the affected areas. Exosome-based drug delivery systems have become an attractive option for targeted therapy in MS. Exosomes, small extracellular vesicles derived from various cell types, possess unique biological properties that make them ideal nanocarriers for delivering therapeutic cargo to specific cell populations in the CNS. In this study, we supply a comprehensive overview of the current advances and future perspectives of exosome-based drug delivery systems for MS. We discuss the biogenesis of exosomes, strategies for cargo loading, engineering approaches to enhance their targeting capabilities, and the potential clinical applications of exosome-mediated drug delivery in MS therapy. Additionally, we explore preclinical studies and animal models that demonstrate the effectiveness of exosome-based drug delivery in ameliorating MS pathology. By highlighting the challenges and opportunities in utilizing exosomes as drug delivery vehicles, this review aims to contribute to the growing body of knowledge in the field of nanomedicine for MS. Considering the potential of exosome-based drug delivery systems to enhance the accessibility, specificity, and effectiveness of therapies while minimizing off-target effects might change the therapeutic scenario for MS.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111256"},"PeriodicalIF":3.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-12DOI: 10.1016/j.brainresbull.2025.111255
Oleh Demianchuk , Maria Bayliak , Myroslava Vatashchuk , Dmytro Gospodaryov , Viktoriia Hurza , Vitalii Derkachov , Vladyslav Berezovskyi , Volodymyr I. Lushchak
Alpha-ketoglutarate (AKG), an intermediate of the tricarboxylic acid cycle, has been found to mitigate oxidative stress and inflammation. In turn, a cafeteria diet (CD), an obesogenic diet, is often associated with oxidative stress and inflammation. This study aimed to determine whether AKG can level the effects of CD on animal behavior, oxidative stress markers, glycolytic flow, and autophagy in the mouse cerebral cortex. Female C57BL/6 J mice were divided into two groups and fed either a standard diet or a CD for eight weeks. For the next four weeks, each group continued to be fed the previous diet; however, half of the individuals within each group received drinking water with 1 % AKG. Using an open field test, we found that the combination of CD and AKG promoted the development of anxiety signs. Both CD and AKG decreased the exploratory behavior of mice, with a significant additive effect in the combined diet. On diets supplemented with AKG, animals produced fewer fecal boli, a measure of emotionality. On all experimental diets, mice had lower activities of antioxidant and related enzymes, with no significant differences in the activities of glycolytic enzymes. The AKG-supplemented diet induced the transcription of autophagy-related genes and targets of the forkhead box O factor, involved in the regulation of carbohydrate metabolism. Transcriptional changes induced by AKG were partly abrogated by the CD. These findings suggest that AKG, particularly when combined with CD, may modulate behavioral responses and oxidative stress intensity in the brain by altering key metabolic and autophagic pathways.
{"title":"Alpha-ketoglutarate promotes anxiety, activates autophagy, and suppresses antioxidant enzymes in the cerebral cortex of female mice on cafeteria diet","authors":"Oleh Demianchuk , Maria Bayliak , Myroslava Vatashchuk , Dmytro Gospodaryov , Viktoriia Hurza , Vitalii Derkachov , Vladyslav Berezovskyi , Volodymyr I. Lushchak","doi":"10.1016/j.brainresbull.2025.111255","DOIUrl":"10.1016/j.brainresbull.2025.111255","url":null,"abstract":"<div><div>Alpha-ketoglutarate (AKG), an intermediate of the tricarboxylic acid cycle, has been found to mitigate oxidative stress and inflammation. In turn, a cafeteria diet (CD), an obesogenic diet, is often associated with oxidative stress and inflammation. This study aimed to determine whether AKG can level the effects of CD on animal behavior, oxidative stress markers, glycolytic flow, and autophagy in the mouse cerebral cortex. Female C57BL/6 J mice were divided into two groups and fed either a standard diet or a CD for eight weeks. For the next four weeks, each group continued to be fed the previous diet; however, half of the individuals within each group received drinking water with 1 % AKG. Using an open field test, we found that the combination of CD and AKG promoted the development of anxiety signs. Both CD and AKG decreased the exploratory behavior of mice, with a significant additive effect in the combined diet. On diets supplemented with AKG, animals produced fewer fecal boli, a measure of emotionality. On all experimental diets, mice had lower activities of antioxidant and related enzymes, with no significant differences in the activities of glycolytic enzymes. The AKG-supplemented diet induced the transcription of autophagy-related genes and targets of the forkhead box O factor, involved in the regulation of carbohydrate metabolism. Transcriptional changes induced by AKG were partly abrogated by the CD. These findings suggest that AKG, particularly when combined with CD, may modulate behavioral responses and oxidative stress intensity in the brain by altering key metabolic and autophagic pathways.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111255"},"PeriodicalIF":3.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-11DOI: 10.1016/j.brainresbull.2025.111246
Donghai Wu , Siying Qu , Haiju Sun , Shuting Zhou , Xinyuan Qu , Yutian Chen , Hantong Hu , Xiaoyu Li
Depression is a common but serious mental health illness affected human’s physiology and psychology. In contemporary times, neurophysiological research on depression has emerged as a prominent area of investigation, yet there remains a paucity of review elucidating the central mechanisms of depression in the brain. Consequently, we undertook a bibliometric analysis and visualization assessment to underscore recent advancements in research pertaining to the neural underpinnings of depression. By employing these methods, we have collected articles spanning the period from 2013 to 2024, shedding light on the latest insights into the brain mechanisms associated with depression. Bibliometric analysis found 16327 research papers in the field of brain mechanism underlying depression, overall showing a sustained growth trend. Through meticulous analysis of collected data on institutions and countries, authors, co-cited literature, keywords, etc., this paper humbly aims to tentatively identify future research hotspots and frontiers, hoping to modestly contribute to and stimulate further scholarly progress in the field.
{"title":"Unveiling the brain mechanism underlying depression: 12 Years of insights from bibliometric and visualization analysis","authors":"Donghai Wu , Siying Qu , Haiju Sun , Shuting Zhou , Xinyuan Qu , Yutian Chen , Hantong Hu , Xiaoyu Li","doi":"10.1016/j.brainresbull.2025.111246","DOIUrl":"10.1016/j.brainresbull.2025.111246","url":null,"abstract":"<div><div>Depression is a common but serious mental health illness affected human’s physiology and psychology. In contemporary times, neurophysiological research on depression has emerged as a prominent area of investigation, yet there remains a paucity of review elucidating the central mechanisms of depression in the brain. Consequently, we undertook a bibliometric analysis and visualization assessment to underscore recent advancements in research pertaining to the neural underpinnings of depression. By employing these methods, we have collected articles spanning the period from 2013 to 2024, shedding light on the latest insights into the brain mechanisms associated with depression. Bibliometric analysis found 16327 research papers in the field of brain mechanism underlying depression, overall showing a sustained growth trend. Through meticulous analysis of collected data on institutions and countries, authors, co-cited literature, keywords, etc., this paper humbly aims to tentatively identify future research hotspots and frontiers, hoping to modestly contribute to and stimulate further scholarly progress in the field.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111246"},"PeriodicalIF":3.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143394645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-10DOI: 10.1016/j.brainresbull.2025.111254
Qiyu Yang , Chunyan Wang , Jingwei Cao , Zhanbin Tang , Shurong Duan
Intracerebral hemorrhage (ICH) is associated with the highest rates of mortality and residual disability. To date, effective treatments to delay or prevent ICH are still lacking. Multiple forms of neuronal cell death have been discovered following ICH, including apoptosis, necrosis, autophagy, and ferroptosis. Aldo-keto reductase family 1 member C1 (AKR1C1) has been identified to act as a protective factor in ferroptosis. However, whether AKR1C1 was involved in the development of ICH was unknown. In this study, the left cerebral striatum of the Sprague-Dawley rat was injected with collagenase type IV to induce an in vivo model. Primary rat cortical neurons treated with oxygen hemoglobin (OxyHb) were applied to as an in vitro model. AKR1C1 was found to be downregulated and immunoreactivity colocalized with NeuN-positive neurons in the perihematomal region. Rats injected with lentiviral particles overexpressing AKR1C1 showed the reduction of cerebral hematoma and the remission of blood-brain barrier disruption. Moreover, AKR1C1 upregulation repressed cell apoptosis and ferroptosis induced by ICH through downregulating the expression of pro-apoptotic factors, inhibiting iron accumulation and lipid peroxidation, along with increasing the expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). The results of in vitro assays were consistent with results from the in vivo. Mechanistically, P53 overexpression augmented the cellular damage in OxyHb-stimulated neurons when AKR1C1 was overexpressed. Taken together, AKR1C1 improves ICH injury by inhibiting neuronal cell death via negatively regulating P53 expression and affecting the SLC7A11/GPX4 pathway.
{"title":"AKR1C1 protects against intracerebral hemorrhage by suppressing neuronal cell death via the P53/SLC7A11/GPX4 axis","authors":"Qiyu Yang , Chunyan Wang , Jingwei Cao , Zhanbin Tang , Shurong Duan","doi":"10.1016/j.brainresbull.2025.111254","DOIUrl":"10.1016/j.brainresbull.2025.111254","url":null,"abstract":"<div><div>Intracerebral hemorrhage (ICH) is associated with the highest rates of mortality and residual disability. To date, effective treatments to delay or prevent ICH are still lacking. Multiple forms of neuronal cell death have been discovered following ICH, including apoptosis, necrosis, autophagy, and ferroptosis. Aldo-keto reductase family 1 member C1 (AKR1C1) has been identified to act as a protective factor in ferroptosis. However, whether AKR1C1 was involved in the development of ICH was unknown. In this study, the left cerebral striatum of the Sprague-Dawley rat was injected with collagenase type IV to induce an <em>in vivo</em> model. Primary rat cortical neurons treated with oxygen hemoglobin (OxyHb) were applied to as an <em>in vitro</em> model. AKR1C1 was found to be downregulated and immunoreactivity colocalized with NeuN-positive neurons in the perihematomal region. Rats injected with lentiviral particles overexpressing AKR1C1 showed the reduction of cerebral hematoma and the remission of blood-brain barrier disruption. Moreover, AKR1C1 upregulation repressed cell apoptosis and ferroptosis induced by ICH through downregulating the expression of pro-apoptotic factors, inhibiting iron accumulation and lipid peroxidation, along with increasing the expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). The results of <em>in vitro</em> assays were consistent with results from the <em>in vivo</em>. Mechanistically, P53 overexpression augmented the cellular damage in OxyHb-stimulated neurons when AKR1C1 was overexpressed. Taken together, AKR1C1 improves ICH injury by inhibiting neuronal cell death via negatively regulating P53 expression and affecting the SLC7A11/GPX4 pathway.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111254"},"PeriodicalIF":3.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peripheral myelination disorders encompass a variety of disorders that affect myelin sheaths in the peripheral nervous system. The Charcot-Marie-Tooth disease (CMT), the most common inherited peripheral neuropathy, is one of the most prevalent among them. CMT stems from a wide range of genetic causes that disrupt the nerve conduction, leading to progressive muscle weakness and atrophy, sensory loss, and motor function impairment. Historically, the study of these disorders has relied heavily on animal studies, owing to the challenges in accessing human cells. However, the advent of human induced pluripotent stem cell (hiPSC)-derived neuronal cells has addressed these limitations in the realm of peripheral myelination disorders. Despite this, obtaining myelin in these models remains an expensive, time-consuming, and material-intensive process. This study presents a novel, cost-effective method utilizing hiPSC-derived Schwann cells and motor neurons in a three-dimensional culture system. Our method successfully enabled the acquisition of myelin in a control clone within just four weeks, as confirmed by electron microscopy. Furthermore, the utility of these approaches was validated by studying CMT4C, also named AR-CMTde-SH3TC2, the most common recessive demyelinating form of CMT. This revealed defects in Schwann cell support to motor neuron neurite outgrowth and impaired myelination in disease-specific hiPSC-derived lines. This approach offers valuable insights into the pathogenesis of peripheral myelination disorders and provides a platform for testing potential therapeutic strategies.
{"title":"Addressing myelination disorders: Novel strategies using human 3D peripheral nerve model","authors":"Camille Loret , Camille Scherrer , Amandine Rovini , Esther Lesage , Laurence Richard , Aurore Danigo , Franck Sturtz , Frédéric Favreau , Pierre-Antoine Faye , Anne-Sophie Lia","doi":"10.1016/j.brainresbull.2025.111252","DOIUrl":"10.1016/j.brainresbull.2025.111252","url":null,"abstract":"<div><div>Peripheral myelination disorders encompass a variety of disorders that affect myelin sheaths in the peripheral nervous system. The Charcot-Marie-Tooth disease (CMT), the most common inherited peripheral neuropathy, is one of the most prevalent among them. CMT stems from a wide range of genetic causes that disrupt the nerve conduction, leading to progressive muscle weakness and atrophy, sensory loss, and motor function impairment. Historically, the study of these disorders has relied heavily on animal studies, owing to the challenges in accessing human cells. However, the advent of human induced pluripotent stem cell (hiPSC)-derived neuronal cells has addressed these limitations in the realm of peripheral myelination disorders. Despite this, obtaining myelin in these models remains an expensive, time-consuming, and material-intensive process. This study presents a novel, cost-effective method utilizing hiPSC-derived Schwann cells and motor neurons in a three-dimensional culture system. Our method successfully enabled the acquisition of myelin in a control clone within just four weeks, as confirmed by electron microscopy. Furthermore, the utility of these approaches was validated by studying CMT4C, also named AR-CMTde-<em>SH3TC2</em>, the most common recessive demyelinating form of CMT. This revealed defects in Schwann cell support to motor neuron neurite outgrowth and impaired myelination in disease-specific hiPSC-derived lines. This approach offers valuable insights into the pathogenesis of peripheral myelination disorders and provides a platform for testing potential therapeutic strategies.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111252"},"PeriodicalIF":3.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Obstructive sleep apnoea syndrome (OSAS) is considered a risk factor for several comorbidities. Alteration in gut microbiome was documented in OSAS animal models and in paediatric patients. This study analysed gut microbiome composition in adult patients with OSAS compared to healthy controls. Further, the effect of excessive daytime sleepiness (EDS) on gut microbiome was evaluated.
Methods
Adult patients with OSAS underwent polysomnographic recording and completed the Epworth Sleepiness Scale (ESS) to assess EDS. Faecal samples were collected and compared between patients and healthy controls. Composition, community diversity, differences in taxa abundance profiles and sample dysbiosis were evaluated through 16S metagenomics and multiple bioinformatics algorithms. OSAS patients were distributed in two groups according to EDS (ESS score≥10) to assess differences in clinical, polysomnographic and faecal data.
Results
Twenty-three OSAS patients were compared to 44 healthy controls. Patients presented significant differences of gut microbiome biodiversity, specifically in qualitative alpha diversity metrics (Faith’s PD Kruskal-Wallis test, p-value=0.003; Number_of_Observed_Features, p-value =0.001). OSAS patients tend to cluster together, at least for Jaccard and Unweighted UniFrac distance-based PERMANOVA tests (q-values=0.02 and =0.003, respectively). Several taxa were detected as different in abundance between OSAS patients and healthy controls, although, globally, OSAS patients cannot be considered as “dysbiotic”. Differences in bacteria composition were evident between OSAS patients with and those without EDS.
Conclusions
OSAS is associated with gut microbiome alteration in adult patients. EDS in OSAS seems to characterize a different gut microbiome composition, although it can be only hypothesized a gut-mediated effect on EDS in OSAS.
{"title":"Gut microbiome composition changes in obstructive sleep apnoea syndrome also in relation to excessive daytime sleepiness","authors":"Mariana Fernandes , Orazio Palmieri , Stefano Castellana , Matteo Spanetta , Tiziana Latiano , Clementina Lupo , Claudia De Masi , Christian Cardile , Carmen Calvello , Francesca Izzi , Fabio Placidi , Tommaso Mazza , Nicola Biagio Mercuri , Anna Latiano , Claudio Liguori","doi":"10.1016/j.brainresbull.2025.111251","DOIUrl":"10.1016/j.brainresbull.2025.111251","url":null,"abstract":"<div><h3>Introduction</h3><div>Obstructive sleep apnoea syndrome (OSAS) is considered a risk factor for several comorbidities. Alteration in gut microbiome was documented in OSAS animal models and in paediatric patients. This study analysed gut microbiome composition in adult patients with OSAS compared to healthy controls. Further, the effect of excessive daytime sleepiness (EDS) on gut microbiome was evaluated.</div></div><div><h3>Methods</h3><div>Adult patients with OSAS underwent polysomnographic recording and completed the Epworth Sleepiness Scale (ESS) to assess EDS. Faecal samples were collected and compared between patients and healthy controls. Composition, community diversity, differences in taxa abundance profiles and sample dysbiosis were evaluated through 16S metagenomics and multiple bioinformatics algorithms. OSAS patients were distributed in two groups according to EDS (ESS score≥10) to assess differences in clinical, polysomnographic and faecal data.</div></div><div><h3>Results</h3><div>Twenty-three OSAS patients were compared to 44 healthy controls. Patients presented significant differences of gut microbiome biodiversity, specifically in qualitative alpha diversity metrics (Faith’s PD Kruskal-Wallis test, p-value=0.003; Number_of_Observed_Features, p-value =0.001). OSAS patients tend to cluster together, at least for Jaccard and Unweighted UniFrac distance-based PERMANOVA tests (q-values=0.02 and =0.003, respectively). Several taxa were detected as different in abundance between OSAS patients and healthy controls, although, globally, OSAS patients cannot be considered as “dysbiotic”. Differences in bacteria composition were evident between OSAS patients with and those without EDS.</div></div><div><h3>Conclusions</h3><div>OSAS is associated with gut microbiome alteration in adult patients. EDS in OSAS seems to characterize a different gut microbiome composition, although it can be only hypothesized a gut-mediated effect on EDS in OSAS.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111251"},"PeriodicalIF":3.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-10DOI: 10.1016/j.brainresbull.2025.111253
Youyang Zhu , Miao Tian , Shiyu Lu , Yuliang Qin , Ting Zhao , Hongling Shi , Zhaofu Li , Dongdong Qin
Neurodegenerative diseases (NDDs) are a class of cognitive and motor disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington's disease (HD), Amyotrophic Lateral Sclerosis (ALS), and others. They are caused by lesions in cells and tissues of the central nervous system, resulting in corresponding dysfunctions and consequent decline in cognitive and motor functions. Neural tissues are extremely vulnerable to oxidative stress, which plays critical biological roles in NDDs. Aromatic compounds are found extensively in natural plants and have substantial effects of anti-oxidative stress damage, which not only have a wide range of research applications in cosmetics, foods, etc., but are also frequently utilized in the treatment of various central nervous system diseases. This review summarizes the relevant oxidative stress mechanisms in NDDs (AD, PD, HD, and ALS) and reviews aromatic compounds such as polyphenols, terpenoids, and flavonoids that can be used in the management of neurodegenerative diseases, as well as their specific mechanisms of antioxidant action. This review will serve as a reference for future experimental studies on neurodegenerative illnesses while also offering fresh insights into clinical therapy.
{"title":"The antioxidant role of aromatic plant extracts in managing neurodegenerative diseases: A comprehensive review","authors":"Youyang Zhu , Miao Tian , Shiyu Lu , Yuliang Qin , Ting Zhao , Hongling Shi , Zhaofu Li , Dongdong Qin","doi":"10.1016/j.brainresbull.2025.111253","DOIUrl":"10.1016/j.brainresbull.2025.111253","url":null,"abstract":"<div><div>Neurodegenerative diseases (NDDs) are a class of cognitive and motor disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington's disease (HD), Amyotrophic Lateral Sclerosis (ALS), and others. They are caused by lesions in cells and tissues of the central nervous system, resulting in corresponding dysfunctions and consequent decline in cognitive and motor functions. Neural tissues are extremely vulnerable to oxidative stress, which plays critical biological roles in NDDs. Aromatic compounds are found extensively in natural plants and have substantial effects of anti-oxidative stress damage, which not only have a wide range of research applications in cosmetics, foods, etc., but are also frequently utilized in the treatment of various central nervous system diseases. This review summarizes the relevant oxidative stress mechanisms in NDDs (AD, PD, HD, and ALS) and reviews aromatic compounds such as polyphenols, terpenoids, and flavonoids that can be used in the management of neurodegenerative diseases, as well as their specific mechanisms of antioxidant action. This review will serve as a reference for future experimental studies on neurodegenerative illnesses while also offering fresh insights into clinical therapy.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111253"},"PeriodicalIF":3.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-07DOI: 10.1016/j.brainresbull.2025.111245
Juan Hu , Qiao Li , Shiqiu Jiang , Yingying Deng , Lan Yang , Mengyu Du , Shuxuan He , Fuxing Xu , Chaoying Yan , Wei Gao , Yansong Li , Yaomin Zhu
Mitochondrial dysfunction and neuronal impairment are hallmark features of Diabetes-Associated Cognitive Dysfunction (DACD), mitochondrial transplantation is also a therapeutic intervention for DACD. However, the precise mechanism underlying its therapeutic effects are not fully elucidated. Given that imbalances in copper homeostasis and cuproptosis are associated with various neurodegenerative disorders and diabetic myocardial damage, we hypothesize a role for cuproptosis in the pathogenesis of DACD. We further propose that therapeutic peripheral mitochondrial transplantation may ameliorate DACD by reducing processes of cuproptosis. In this research, the study delved into the expression levels of cuproptosis-associated proteins FDX1, LIAS, and DLAT, as well as the copper content in both type 2 diabetes mellitus (T2DM) mice and primary neuronal cells exposed to high glucose and palmitic acid (HG/Pal). Furthermore, the cognitive capabilities of the mice were evaluated using a series of behavioral tests. The findings revealed that in primary neurons exposed to HG/Pal, the expression of copper levels was elevated, and the levels of FDX1, LIAS, and DLAT were reduced. Post-transplantation of platelet-derived mitochondria (Mito-Plt), a significant reversal of these biomarkers was noted, coincident with an improvement in cognitive deficits in T2DM mice. Significantly, the cuproptosis agonist elesclomol (ES) aggravated these alterations. In summary, the findings collectively suggest a causal connection between DACD and the development of cuproptosis in neurons. The use of exogenous Mito-Plt presents a promising therapeutic approach, capable of rescuing neurons from cuproptosis and thereby potentially alleviating DACD.
{"title":"Peripheral mitochondrial transplantation alleviates diabetes-associated cognitive dysfunction by suppressing cuproptosis","authors":"Juan Hu , Qiao Li , Shiqiu Jiang , Yingying Deng , Lan Yang , Mengyu Du , Shuxuan He , Fuxing Xu , Chaoying Yan , Wei Gao , Yansong Li , Yaomin Zhu","doi":"10.1016/j.brainresbull.2025.111245","DOIUrl":"10.1016/j.brainresbull.2025.111245","url":null,"abstract":"<div><div>Mitochondrial dysfunction and neuronal impairment are hallmark features of Diabetes-Associated Cognitive Dysfunction (DACD), mitochondrial transplantation is also a therapeutic intervention for DACD. However, the precise mechanism underlying its therapeutic effects are not fully elucidated. Given that imbalances in copper homeostasis and cuproptosis are associated with various neurodegenerative disorders and diabetic myocardial damage, we hypothesize a role for cuproptosis in the pathogenesis of DACD. We further propose that therapeutic peripheral mitochondrial transplantation may ameliorate DACD by reducing processes of cuproptosis. In this research, the study delved into the expression levels of cuproptosis-associated proteins FDX1, LIAS, and DLAT, as well as the copper content in both type 2 diabetes mellitus (T2DM) mice and primary neuronal cells exposed to high glucose and palmitic acid (HG/Pal). Furthermore, the cognitive capabilities of the mice were evaluated using a series of behavioral tests. The findings revealed that in primary neurons exposed to HG/Pal, the expression of copper levels was elevated, and the levels of FDX1, LIAS, and DLAT were reduced. Post-transplantation of platelet-derived mitochondria (Mito-Plt), a significant reversal of these biomarkers was noted, coincident with an improvement in cognitive deficits in T2DM mice. Significantly, the cuproptosis agonist elesclomol (ES) aggravated these alterations. In summary, the findings collectively suggest a causal connection between DACD and the development of cuproptosis in neurons. The use of exogenous Mito-Plt presents a promising therapeutic approach, capable of rescuing neurons from cuproptosis and thereby potentially alleviating DACD.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111245"},"PeriodicalIF":3.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143376606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号