Despite decades of intensive research, effective treatment and prevention strategies for neurodegenerative diseases (NDDs) remain elusive. This review focuses on Alzheimer’s and Parkinson’s diseases and acquired epilepsy suggesting that in their early phase, these progressive pathologies share common or interacting molecular pathways. Indeed, oxidative stress associated with disrupted glucose metabolism is the expected end state of most, if not all, risk factors preceding the onset of major NDDs. This review proposes that the initial oxidative stress in the brain resulting specifically from the hyperactivation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) causes a decline in glucose utilization and is the primary initiating factor of major NDDs. The existing clinical and experimental evidence points to NOX as the primary initiating mechanism shared within the major NDDs. During early oxidative stress, NOX activation is triggered in variable brain cells via multiple pathways, from beta-amyloid to alpha-synuclein, fibrin to glutamate and seizures. Therefore, the treatment strategy should have targeted the activation of NOX, wouldn’t there be a lack of clinically approved selective NOX antagonists? On the other hand, there are promising metabolism-altering approaches via dietary means able to switch energy intake from glucose to ketones, which influences both oxidative stress and glucose utilization and could ameliorate disease progression. The regimen of time-restricted eating appears to be the most feasible, nutritious, and palatable one providing the essential benefits of a ketogenic diet without adverse effects.
{"title":"Metabolic correction of neurodegenerative pathologies: the role of macronutrients and timing","authors":"Y. Zilberter, T. Zilberter","doi":"10.37349/en.2023.00013","DOIUrl":"https://doi.org/10.37349/en.2023.00013","url":null,"abstract":"Despite decades of intensive research, effective treatment and prevention strategies for neurodegenerative diseases (NDDs) remain elusive. This review focuses on Alzheimer’s and Parkinson’s diseases and acquired epilepsy suggesting that in their early phase, these progressive pathologies share common or interacting molecular pathways. Indeed, oxidative stress associated with disrupted glucose metabolism is the expected end state of most, if not all, risk factors preceding the onset of major NDDs. This review proposes that the initial oxidative stress in the brain resulting specifically from the hyperactivation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) causes a decline in glucose utilization and is the primary initiating factor of major NDDs. The existing clinical and experimental evidence points to NOX as the primary initiating mechanism shared within the major NDDs. During early oxidative stress, NOX activation is triggered in variable brain cells via multiple pathways, from beta-amyloid to alpha-synuclein, fibrin to glutamate and seizures. Therefore, the treatment strategy should have targeted the activation of NOX, wouldn’t there be a lack of clinically approved selective NOX antagonists? On the other hand, there are promising metabolism-altering approaches via dietary means able to switch energy intake from glucose to ketones, which influences both oxidative stress and glucose utilization and could ameliorate disease progression. The regimen of time-restricted eating appears to be the most feasible, nutritious, and palatable one providing the essential benefits of a ketogenic diet without adverse effects.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81662074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Gerhard, Richard Sharples, Tsepo Goerttler, K. McDonald, E. Visi, R. Hinz, F. Turkheimer, Isabel Lewzey, K. Herholz, A. Jacobs, C. Holmes
Aim: Microglial activation is increasingly recognised as a factor in the progression of Alzheimer’s disease (AD) and may be modified by systemic inflammatory signals including serum tumour necrosis factor (TNF)-α. The aim was to investigate whether blockade of peripheral TNF-α with peripheral inhibitors such as etanercept reduces microglial activation in prodromal AD. Methods: A one-year, multi-centre, phase 2, double-blind randomised placebo-controlled trial (RPCT) was performed, to assess the effect of weekly 50 mg s.c. etanercept in amyloid positive mild cognitive impaired participants on the change in microglial activation as measured by [11C](R)-PK11195 positron emission tomography (PET). Secondary objectives were to ascertain the change in cortical amyloid load on PET and the change in the Montreal Cognitive Assessment (MoCA). Results: Forty-four subjects consented to the study. Twenty-eight subjects failed screening including six subjects who were amyloid negative on visual read of the AmyvidTM PET scans. Thirteen of sixteen subjects with mild cognitive impairment (MCI) due to AD completed the baseline [11C](R)-PK11195 PET scan and were randomised to either placebo or etanercept. Three patients who consented were not able to complete screening due to early termination of the study following delays in study commencement. [11C](R)-PK11195 binding potential (BP) at baseline showed an almost global increase in MCI patients as compared to age-matched controls. Compliance to medication was high over the twelve-month trial period with etanercept being well tolerated. The study did not achieve statistical power to show a significant effect of etanercept over 52 weeks in the limited number of patients with MCI on microglial activation as measured by [11C](R)-PK11195 PET. Overall uptake of florbetapir in the follow up (FU) scans remained stable. The study was not powered to show statistical differences in psychometric ratings between groups. Conclusions: This study did not show evidence that treatment with etanercept over one year would modulate microglial activation in amyloid positive MCI patients (EudraCT identifier: 2015-002145-63, https://www.clinicaltrialsregister.eu; International Standard Randomised Controlled Trial Number identifier: ISRCTN12472821, https://www.isrctn.com).
{"title":"The effect of the tumour necrosis factor-alpha-inhibitor etanercept on microglial activation patients with mild cognitive impairment—a PET study","authors":"A. Gerhard, Richard Sharples, Tsepo Goerttler, K. McDonald, E. Visi, R. Hinz, F. Turkheimer, Isabel Lewzey, K. Herholz, A. Jacobs, C. Holmes","doi":"10.37349/en.2023.00012","DOIUrl":"https://doi.org/10.37349/en.2023.00012","url":null,"abstract":"Aim: Microglial activation is increasingly recognised as a factor in the progression of Alzheimer’s disease (AD) and may be modified by systemic inflammatory signals including serum tumour necrosis factor (TNF)-α. The aim was to investigate whether blockade of peripheral TNF-α with peripheral inhibitors such as etanercept reduces microglial activation in prodromal AD.\u0000Methods: A one-year, multi-centre, phase 2, double-blind randomised placebo-controlled trial (RPCT) was performed, to assess the effect of weekly 50 mg s.c. etanercept in amyloid positive mild cognitive impaired participants on the change in microglial activation as measured by [11C](R)-PK11195 positron emission tomography (PET). Secondary objectives were to ascertain the change in cortical amyloid load on PET and the change in the Montreal Cognitive Assessment (MoCA).\u0000Results: Forty-four subjects consented to the study. Twenty-eight subjects failed screening including six subjects who were amyloid negative on visual read of the AmyvidTM PET scans. Thirteen of sixteen subjects with mild cognitive impairment (MCI) due to AD completed the baseline [11C](R)-PK11195 PET scan and were randomised to either placebo or etanercept. Three patients who consented were not able to complete screening due to early termination of the study following delays in study commencement. [11C](R)-PK11195 binding potential (BP) at baseline showed an almost global increase in MCI patients as compared to age-matched controls. Compliance to medication was high over the twelve-month trial period with etanercept being well tolerated. The study did not achieve statistical power to show a significant effect of etanercept over 52 weeks in the limited number of patients with MCI on microglial activation as measured by [11C](R)-PK11195 PET. Overall uptake of florbetapir in the follow up (FU) scans remained stable. The study was not powered to show statistical differences in psychometric ratings between groups.\u0000Conclusions: This study did not show evidence that treatment with etanercept over one year would modulate microglial activation in amyloid positive MCI patients (EudraCT identifier: 2015-002145-63, https://www.clinicaltrialsregister.eu; International Standard Randomised Controlled Trial Number identifier: ISRCTN12472821, https://www.isrctn.com).","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87611369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Treatment concept successfully translated into human patients","authors":"D. Hermann","doi":"10.37349/en.2023.00011","DOIUrl":"https://doi.org/10.37349/en.2023.00011","url":null,"abstract":"","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"75 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73416193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Ruscu, Daiana Burdusel, Andreea-Mihaela Cercel, M. Aldea, D. Hermann, Israel Fernández Cadenas, T. Doeppner, R. Surugiu, A. Popa-Wagner
Aim: Stroke is one of the leading causes of death and disability worldwide. Plasma biomarkers have long been used to evaluate physiological or pathological processes and to make predictions about the outcome of stroke patients. The current systematic review is focused on genetic plasma biomarkers as a new potential prognostic indicator for post-stroke recovery. The aim of the present systematic review is to assess the potential of genetic plasma biomarkers associated with stroke to predict post-stroke recovery. Methods: The search strategy used PubMed and Web of Science databases to identified 166 studies that investigated genetic plasma biomarkers in patients with stroke between 2017 and 2021. However, only 21 of them met the inclusion criteria. Results: The identified genetic biomarkers can be divided into: (i) serum/plasma circular RNA (circRNA) associated with stroke onset or recurrence (5; 23.80%), (ii) genetic polymorphisms associated with the atherosclerotic process and stroke recurrence (6; 28.57%), (iii) serum/plasma long non-coding RNA (lncRNA) levels involved in immunity/inflammatory processes (4; 19.04%), (iv) marker of DNA methylation associated with stroke onset and outcome (3; 14.28%), and (v) proteins and pathways of stroke identified by serum/ plasma proteomics/genomics analysis (3; 14.28%). Conclusions: Overall, more than 100 potential biomarkers were found and the data suggest that combinations of plasma genetic biomarkers might be used as a better predictor for stroke.
目的:中风是世界范围内导致死亡和残疾的主要原因之一。长期以来，血浆生物标志物一直被用于评估脑卒中患者的生理或病理过程，并预测其预后。目前的系统综述集中在遗传血浆生物标志物作为脑卒中后恢复的新的潜在预后指标。本系统综述的目的是评估与中风相关的遗传血浆生物标志物在预测中风后恢复方面的潜力。方法:检索策略使用PubMed和Web of Science数据库，确定了2017年至2021年间卒中患者遗传血浆生物标志物的166项研究。然而，其中只有21个符合纳入标准。结果:鉴定的遗传生物标志物可分为:(i)与卒中发作或复发相关的血清/血浆环状RNA (circRNA) (5;23.80%)， (ii)与动脉粥样硬化过程和卒中复发相关的遗传多态性(6;28.57%)， (iii)参与免疫/炎症过程的血清/血浆长链非编码RNA (lncRNA)水平(4;19.04%)， (iv)与中风发病和结局相关的DNA甲基化标志物(3;14.28%)，以及(v)通过血清/血浆蛋白质组学/基因组学分析确定的中风蛋白质和途径(3;14.28%)。结论:总的来说，发现了100多种潜在的生物标志物，数据表明，血浆遗传生物标志物的组合可能被用作更好的中风预测指标。
{"title":"Genetic plasma biomarkers associated with ischemic stroke","authors":"M. Ruscu, Daiana Burdusel, Andreea-Mihaela Cercel, M. Aldea, D. Hermann, Israel Fernández Cadenas, T. Doeppner, R. Surugiu, A. Popa-Wagner","doi":"10.37349/en.2023.00010","DOIUrl":"https://doi.org/10.37349/en.2023.00010","url":null,"abstract":"Aim: Stroke is one of the leading causes of death and disability worldwide. Plasma biomarkers have long been used to evaluate physiological or pathological processes and to make predictions about the outcome of stroke patients. The current systematic review is focused on genetic plasma biomarkers as a new potential prognostic indicator for post-stroke recovery. The aim of the present systematic review is to assess the potential of genetic plasma biomarkers associated with stroke to predict post-stroke recovery.\u0000Methods: The search strategy used PubMed and Web of Science databases to identified 166 studies that investigated genetic plasma biomarkers in patients with stroke between 2017 and 2021. However, only 21 of them met the inclusion criteria.\u0000Results: The identified genetic biomarkers can be divided into: (i) serum/plasma circular RNA (circRNA) associated with stroke onset or recurrence (5; 23.80%), (ii) genetic polymorphisms associated with the atherosclerotic process and stroke recurrence (6; 28.57%), (iii) serum/plasma long non-coding RNA (lncRNA) levels involved in immunity/inflammatory processes (4; 19.04%), (iv) marker of DNA methylation associated with stroke onset and outcome (3; 14.28%), and (v) proteins and pathways of stroke identified by serum/ plasma proteomics/genomics analysis (3; 14.28%).\u0000Conclusions: Overall, more than 100 potential biomarkers were found and the data suggest that combinations of plasma genetic biomarkers might be used as a better predictor for stroke.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75711074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01Epub Date: 2023-02-23DOI: 10.37349/en.2023.00009
Matthew Willman, Jonathan Willman, John Figg, Emma Dioso, Sai Sriram, Bankole Olowofela, Kevin Chacko, Jairo Hernandez, Brandon Lucke-Wold
Astrocytomas include a wide range of tumors with unique mutations and varying grades of malignancy. These tumors all originate from the astrocyte, a star-shaped glial cell that plays a major role in supporting functions of the central nervous system (CNS), including blood-brain barrier (BBB) development and maintenance, water and ion regulation, influencing neuronal synaptogenesis, and stimulating the immunological response. In terms of epidemiology, glioblastoma (GB), the most common and malignant astrocytoma, generally occur with higher rates in Australia, Western Europe, and Canada, with the lowest rates in Southeast Asia. Additionally, significantly higher rates of GB are observed in males and non-Hispanic whites. It has been suggested that higher levels of testosterone observed in biological males may account for the increased rates of GB. Hereditary syndromes such as Cowden, Lynch, Turcot, Li-Fraumeni, and neurofibromatosis type 1 have been linked to increased rates of astrocytoma development. While there are a number of specific gene mutations that may influence malignancy or be targeted in astrocytoma treatment, O6-methylguanine-DNA methyltransferase (MGMT) gene function is an important predictor of astrocytoma response to chemotherapeutic agent temozolomide (TMZ). TMZ for primary and bevacizumab in the setting of recurrent tumor formation are two of the main chemotherapeutic agents currently approved in the treatment of astrocytomas. While stereotactic radiosurgery (SRS) has debatable implications for increased survival in comparison to whole-brain radiotherapy (WBRT), SRS demonstrates increased precision with reduced radiation toxicity. When considering surgical resection of astrocytoma, the extent of resection (EoR) is taken into consideration. Subtotal resection (STR) spares the margins of the T1 enhanced magnetic resonance imaging (MRI) region, gross total resection (GTR) includes the margins, and supramaximal resection (SMR) extends beyond the margin of the T1 and into the T2 region. Surgical resection, radiation, and chemotherapy are integral components of astrocytoma treatment.
{"title":"Update for astrocytomas: medical and surgical management considerations.","authors":"Matthew Willman, Jonathan Willman, John Figg, Emma Dioso, Sai Sriram, Bankole Olowofela, Kevin Chacko, Jairo Hernandez, Brandon Lucke-Wold","doi":"10.37349/en.2023.00009","DOIUrl":"10.37349/en.2023.00009","url":null,"abstract":"<p><p>Astrocytomas include a wide range of tumors with unique mutations and varying grades of malignancy. These tumors all originate from the astrocyte, a star-shaped glial cell that plays a major role in supporting functions of the central nervous system (CNS), including blood-brain barrier (BBB) development and maintenance, water and ion regulation, influencing neuronal synaptogenesis, and stimulating the immunological response. In terms of epidemiology, glioblastoma (GB), the most common and malignant astrocytoma, generally occur with higher rates in Australia, Western Europe, and Canada, with the lowest rates in Southeast Asia. Additionally, significantly higher rates of GB are observed in males and non-Hispanic whites. It has been suggested that higher levels of testosterone observed in biological males may account for the increased rates of GB. Hereditary syndromes such as Cowden, Lynch, Turcot, Li-Fraumeni, and neurofibromatosis type 1 have been linked to increased rates of astrocytoma development. While there are a number of specific gene mutations that may influence malignancy or be targeted in astrocytoma treatment, <i>O</i> <sup>6</sup>-methylguanine-DNA methyltransferase (<i>MGMT</i>) gene function is an important predictor of astrocytoma response to chemotherapeutic agent temozolomide (TMZ). TMZ for primary and bevacizumab in the setting of recurrent tumor formation are two of the main chemotherapeutic agents currently approved in the treatment of astrocytomas. While stereotactic radiosurgery (SRS) has debatable implications for increased survival in comparison to whole-brain radiotherapy (WBRT), SRS demonstrates increased precision with reduced radiation toxicity. When considering surgical resection of astrocytoma, the extent of resection (EoR) is taken into consideration. Subtotal resection (STR) spares the margins of the T1 enhanced magnetic resonance imaging (MRI) region, gross total resection (GTR) includes the margins, and supramaximal resection (SMR) extends beyond the margin of the T1 and into the T2 region. Surgical resection, radiation, and chemotherapy are integral components of astrocytoma treatment.</p>","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"2 ","pages":"1-26"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9163075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Exposure to stressful conditions plays a critical role in brain processes, including neural plasticity, synaptic transmission, and cognitive functions. Since memory-related brain regions, the hippocampus (Hip), the amygdala, and the prefrontal cortex, express high glucocorticoid receptors (GRs), these areas are the potential targets of stress hormones. Stress affects memory encoding, consolidation, and retrieval, which may depend on many factors such as the type, duration, the intensity of the stressor or the brain region. Here, this review mainly focused on the mechanisms involved in stress-induced memory impairment. Acute/chronic stress induces structural and functional changes in neurons and glial cells. Dendritic arborization, reduction of dendritic spine density, and alteration in glutamatergic-mediated synaptic transmission via N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors are mechanisms that stress affect long-term memory formation. Exposure to acute or chronic stress could interplay with multiple neurotransmitter signaling, modulating the neuronal circuits involved in memory impairment or state-dependent learning. Stress hormones also modulate the expression of microRNAs in the specific brain regions responsible for stress-induced behaviors. Because of expressing GRs in astrocytes and microglial cells, stress could affect the morphology, structure, and functions of these glial cells in memory-related brain regions. Astrocytes play a crucial role in stress-induced aversive or fear memory formation. Over-activation of the microglial cells enhances the release of inflammatory cytokines, which results in neuronal injury. Stress has a prominent role in cognitive decline to induces memory problems, particularly in older adults. Due to the issue’s importance, here the provided overview attempted to address the question of how stress alters neuronal epigenetic regulators, synaptic transmissions, and glial activity in the brain.
暴露在压力条件下在大脑过程中起着至关重要的作用，包括神经可塑性、突触传递和认知功能。由于记忆相关的大脑区域，海马体(髋关节)，杏仁核和前额皮质，表达高糖皮质激素受体(GRs)，这些区域是应激激素的潜在目标。压力影响记忆的编码、巩固和提取，这可能取决于许多因素，如压力源的类型、持续时间、强度或大脑区域。本文主要就应激性记忆障碍的机制进行综述。急性/慢性应激诱导神经元和神经胶质细胞的结构和功能改变。树突乔木化、树突棘密度降低以及谷氨酸能介导的n -甲基- d -天冬氨酸(NMDA)和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)受体突触传递的改变是应激影响长期记忆形成的机制。暴露于急性或慢性压力下可能与多种神经递质信号相互作用，调节涉及记忆障碍或状态依赖性学习的神经回路。应激激素还可以调节大脑中负责应激诱发行为的特定区域的microrna的表达。由于星形胶质细胞和小胶质细胞表达GRs，应激可影响记忆相关脑区胶质细胞的形态、结构和功能。星形胶质细胞在应激诱导的厌恶或恐惧记忆形成中起着至关重要的作用。过度激活的小胶质细胞增加了炎性细胞因子的释放，从而导致神经元损伤。压力在认知能力下降中扮演着重要的角色，从而引发记忆问题，尤其是在老年人中。由于这个问题的重要性，这里提供的概述试图解决压力如何改变神经元表观遗传调节，突触传递和大脑中的神经胶质活动的问题。
{"title":"Cellular and molecular mechanisms of stress-induced memory impairment","authors":"A. Rezayof, M. Sardari, S. Hashemizadeh","doi":"10.37349/en.2022.00008","DOIUrl":"https://doi.org/10.37349/en.2022.00008","url":null,"abstract":"Exposure to stressful conditions plays a critical role in brain processes, including neural plasticity, synaptic transmission, and cognitive functions. Since memory-related brain regions, the hippocampus (Hip), the amygdala, and the prefrontal cortex, express high glucocorticoid receptors (GRs), these areas are the potential targets of stress hormones. Stress affects memory encoding, consolidation, and retrieval, which may depend on many factors such as the type, duration, the intensity of the stressor or the brain region. Here, this review mainly focused on the mechanisms involved in stress-induced memory impairment. Acute/chronic stress induces structural and functional changes in neurons and glial cells. Dendritic arborization, reduction of dendritic spine density, and alteration in glutamatergic-mediated synaptic transmission via N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors are mechanisms that stress affect long-term memory formation. Exposure to acute or chronic stress could interplay with multiple neurotransmitter signaling, modulating the neuronal circuits involved in memory impairment or state-dependent learning. Stress hormones also modulate the expression of microRNAs in the specific brain regions responsible for stress-induced behaviors. Because of expressing GRs in astrocytes and microglial cells, stress could affect the morphology, structure, and functions of these glial cells in memory-related brain regions. Astrocytes play a crucial role in stress-induced aversive or fear memory formation. Over-activation of the microglial cells enhances the release of inflammatory cytokines, which results in neuronal injury. Stress has a prominent role in cognitive decline to induces memory problems, particularly in older adults. Due to the issue’s importance, here the provided overview attempted to address the question of how stress alters neuronal epigenetic regulators, synaptic transmissions, and glial activity in the brain.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83626080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The therapy of many neurological disorders has advanced markedly during recent decades. Not so for neurodegenerative disorders. Early detection, deep individual genotyping and phenotyping, and personalized therapies have been suggested as the way forward. However, we still do not know enough about the aetiology and molecular basics of these diseases. In fact, the term neurodegenerative disorder may be a misleading categorization that constitutes a major cognitive barrier against better characterization and understanding of these disorders. Therefore, we need to go back to the basics and employ novel, open-minded observational study protocols that combine very extensive and robust clinical, molecular and epidemiological data collection methods. Moreover, we need to reconsider our basic orientation towards these diseases to increase our chances of finding out what we are actually trying to care for and cure.
{"title":"Should we rethink neurodegeneration?","authors":"J. Sipilä","doi":"10.37349/en.2022.00006","DOIUrl":"https://doi.org/10.37349/en.2022.00006","url":null,"abstract":"The therapy of many neurological disorders has advanced markedly during recent decades. Not so for neurodegenerative disorders. Early detection, deep individual genotyping and phenotyping, and personalized therapies have been suggested as the way forward. However, we still do not know enough about the aetiology and molecular basics of these diseases. In fact, the term neurodegenerative disorder may be a misleading categorization that constitutes a major cognitive barrier against better characterization and understanding of these disorders. Therefore, we need to go back to the basics and employ novel, open-minded observational study protocols that combine very extensive and robust clinical, molecular and epidemiological data collection methods. Moreover, we need to reconsider our basic orientation towards these diseases to increase our chances of finding out what we are actually trying to care for and cure.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79082847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ischemic stroke is a highly prevalent condition that frequently results in life-long disability and death. Considerable efforts have been made to establish treatments that prevent secondary ischemic damage and promote stroke recovery. Until now, the recanalization of occluded blood vessels via thrombolysis and thrombectomy, although highly potent, remains the only treatment in humans that enhances stroke outcome. Small extracellular vesicles are non-replicating, nano-sized (70–150 nm) lipid bilayer-enclosed vesicles, which have shown remarkable biological activities in various physiological and pathophysiological contexts. When administered post-stroke, mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) induce neuroprotection, promote brain remodeling and plasticity, and enhance neurological recovery in rodents and non-human primates via mechanisms that involve immunomodulation and anti-inflammation. In this review, experimental studies on the therapeutic actions of MSC-EVs in animal stroke models are summarized and perspectives for clinical translation are outlined.
{"title":"Neuroprotective and neurorestorative actions of mesenchymal stromal cell-derived small extracellular vesicles in the ischemic brain","authors":"Chen Wang, B. Giebel, D. Hermann","doi":"10.37349/en.2022.00005","DOIUrl":"https://doi.org/10.37349/en.2022.00005","url":null,"abstract":"Ischemic stroke is a highly prevalent condition that frequently results in life-long disability and death. Considerable efforts have been made to establish treatments that prevent secondary ischemic damage and promote stroke recovery. Until now, the recanalization of occluded blood vessels via thrombolysis and thrombectomy, although highly potent, remains the only treatment in humans that enhances stroke outcome. Small extracellular vesicles are non-replicating, nano-sized (70–150 nm) lipid bilayer-enclosed vesicles, which have shown remarkable biological activities in various physiological and pathophysiological contexts. When administered post-stroke, mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) induce neuroprotection, promote brain remodeling and plasticity, and enhance neurological recovery in rodents and non-human primates via mechanisms that involve immunomodulation and anti-inflammation. In this review, experimental studies on the therapeutic actions of MSC-EVs in animal stroke models are summarized and perspectives for clinical translation are outlined.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79431416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This brief statement describes some recent achievements of neuropathological research, with the focus on Alzheimer’s and other age-related diseases, neurodegenerative disorders (tauopathies, synucleinopathies), multimorbidity of the aged brain, multiple sclerosis (MS), and other neuroinflammatory disorders, including central nervous system involvement by coronavirus disease 2019 (COVID-19), as well as new developments in neurovascular diseases, neurooncology, and myopathies. Although neuropathology, using modern technologies, such as cryo-electron microscopy, proteomic and experimental methods, has helped to increase diagnostic accuracy and provided insight into the pathogenesis of many neurological disorders, future studies in co-operation with clinical and other neurosciences should overcome the challenges of disease-influencing therapeutic approaches.
{"title":"Recent developments and future perspectives of neuropathology","authors":"K. Jellinger","doi":"10.37349/en.2022.00004","DOIUrl":"https://doi.org/10.37349/en.2022.00004","url":null,"abstract":"This brief statement describes some recent achievements of neuropathological research, with the focus on Alzheimer’s and other age-related diseases, neurodegenerative disorders (tauopathies, synucleinopathies), multimorbidity of the aged brain, multiple sclerosis (MS), and other neuroinflammatory disorders, including central nervous system involvement by coronavirus disease 2019 (COVID-19), as well as new developments in neurovascular diseases, neurooncology, and myopathies. Although neuropathology, using modern technologies, such as cryo-electron microscopy, proteomic and experimental methods, has helped to increase diagnostic accuracy and provided insight into the pathogenesis of many neurological disorders, future studies in co-operation with clinical and other neurosciences should overcome the challenges of disease-influencing therapeutic approaches.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87093902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
All living organisms exhibit circadian rhythms. Humans show circadian rhythm of the different physiological functions such as sleep-wake cycle, core body temperature, feeding behavior, metabolic activity, heart rate variability, hormone secretion, and others. The hypothalamic suprachiasmatic nucleus (SCN) acts as a primary circadian pacemaker. Peripheral tissues have an endogenous circadian clock; however, SCN synchronizes the circadian activity of the peripheral clocks. The retinohypothalamic tract (RHT) from retinal ganglionic cells carries the photic signal into the SCN that regulates the rhythmic expression of the core clock genes through the feedback loop. At the output level, the SCN connects with the pineal gland and the peripheral tissues with the help of neuroendocrine mediators. Disruption of circadian clock functions is detrimental to health. Shift work, night work, chronic or acute jet lag, and light-at-night have adverse effects on circadian functions. Misalignment of circadian rhythm alters the expression of core clock genes, leading to deregulation of cellular activity and metabolic functions. Circadian rhythm dysfunction causes many pathologic conditions, including sleep disorders, cardiovascular problems, metabolic dysfunction, infertility, poor physical performance, as well as cancer. The present work has reviewed the relationship between circadian clock dysfunction and impaired physiological activities.
{"title":"Impact of circadian clock dysfunction on human health","authors":"S. Samanta, Sk Asif Ali","doi":"10.37349/en.2022.00002","DOIUrl":"https://doi.org/10.37349/en.2022.00002","url":null,"abstract":"All living organisms exhibit circadian rhythms. Humans show circadian rhythm of the different physiological functions such as sleep-wake cycle, core body temperature, feeding behavior, metabolic activity, heart rate variability, hormone secretion, and others. The hypothalamic suprachiasmatic nucleus (SCN) acts as a primary circadian pacemaker. Peripheral tissues have an endogenous circadian clock; however, SCN synchronizes the circadian activity of the peripheral clocks. The retinohypothalamic tract (RHT) from retinal ganglionic cells carries the photic signal into the SCN that regulates the rhythmic expression of the core clock genes through the feedback loop. At the output level, the SCN connects with the pineal gland and the peripheral tissues with the help of neuroendocrine mediators. Disruption of circadian clock functions is detrimental to health. Shift work, night work, chronic or acute jet lag, and light-at-night have adverse effects on circadian functions. Misalignment of circadian rhythm alters the expression of core clock genes, leading to deregulation of cellular activity and metabolic functions. Circadian rhythm dysfunction causes many pathologic conditions, including sleep disorders, cardiovascular problems, metabolic dysfunction, infertility, poor physical performance, as well as cancer. The present work has reviewed the relationship between circadian clock dysfunction and impaired physiological activities.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"64 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72791906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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