Maya Z Freeman, Deanna N. Cannizzaro, Lydia F Naughton, C. Bove
Fluoroquinolones (FQs) are a broad class of antibiotics typically prescribed for bacterial infections, including infections for which their use is discouraged. The FDA has proposed the existence of a permanent disability (Fluoroquinolone Associated Disability; FQAD), which is yet to be formally recognized. Previous studies suggest that FQs act as selective GABAA receptor inhibitors, preventing the binding of GABA in the central nervous system. GABA is a key regulator of the vagus nerve, involved in the control of gastrointestinal (GI) function. Indeed, GABA is released from the Nucleus of the Tractus Solitarius (NTS) to the Dorsal Motor Nucleus of the vagus (DMV) to tonically regulate vagal activity. The purpose of this review is to summarize the current knowledge on FQs in the context of the vagus nerve and examine how these drugs could lead to dysregulated signaling to the GI tract. Since there is sufficient evidence to suggest that GABA transmission is hindered by FQs, it is reasonable to postulate that the vagal circuit could be compromised at the NTS-DMV synapse after FQ use, possibly leading to the development of permanent GI disorders in FQAD.
{"title":"Fluoroquinolones-Associated Disability: It Is Not All in Your Head","authors":"Maya Z Freeman, Deanna N. Cannizzaro, Lydia F Naughton, C. Bove","doi":"10.3390/NEUROSCI2030017","DOIUrl":"https://doi.org/10.3390/NEUROSCI2030017","url":null,"abstract":"Fluoroquinolones (FQs) are a broad class of antibiotics typically prescribed for bacterial infections, including infections for which their use is discouraged. The FDA has proposed the existence of a permanent disability (Fluoroquinolone Associated Disability; FQAD), which is yet to be formally recognized. Previous studies suggest that FQs act as selective GABAA receptor inhibitors, preventing the binding of GABA in the central nervous system. GABA is a key regulator of the vagus nerve, involved in the control of gastrointestinal (GI) function. Indeed, GABA is released from the Nucleus of the Tractus Solitarius (NTS) to the Dorsal Motor Nucleus of the vagus (DMV) to tonically regulate vagal activity. The purpose of this review is to summarize the current knowledge on FQs in the context of the vagus nerve and examine how these drugs could lead to dysregulated signaling to the GI tract. Since there is sufficient evidence to suggest that GABA transmission is hindered by FQs, it is reasonable to postulate that the vagal circuit could be compromised at the NTS-DMV synapse after FQ use, possibly leading to the development of permanent GI disorders in FQAD.","PeriodicalId":74294,"journal":{"name":"NeuroSci","volume":"122 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83340907","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}
In this paper I will address questions about will, agency, choice, consciousness, relevant brain regions, impacts of disorders, and their therapeutics, and I will do this by referring to my theory, Dual-brain Psychology, which posits that within most of us there exist two mental agencies with different experiences, wills, choices, and behaviors. Each of these agencies is associated as a trait with one brain hemisphere (either left or right) and its composite regions. One of these agencies is more adversely affected by past traumas, and is more immature and more symptomatic, while the other is more mature and healthier. The theory has extensive experimental support through 17 peer-reviewed publications with clinical and non-clinical research. I will discuss how this theory relates to the questions about the nature of agency and I will also discuss my published theory on the physical nature of subjective experience and its relation to the brain, and how that theory interacts with Dual-Brain Psychology, leading to further insights into our human nature and its betterment.
{"title":"A Dual Mind Approach to Understanding the Conscious Self and Its Treatment","authors":"F. Schiffer","doi":"10.3390/NEUROSCI2020016","DOIUrl":"https://doi.org/10.3390/NEUROSCI2020016","url":null,"abstract":"In this paper I will address questions about will, agency, choice, consciousness, relevant brain regions, impacts of disorders, and their therapeutics, and I will do this by referring to my theory, Dual-brain Psychology, which posits that within most of us there exist two mental agencies with different experiences, wills, choices, and behaviors. Each of these agencies is associated as a trait with one brain hemisphere (either left or right) and its composite regions. One of these agencies is more adversely affected by past traumas, and is more immature and more symptomatic, while the other is more mature and healthier. The theory has extensive experimental support through 17 peer-reviewed publications with clinical and non-clinical research. I will discuss how this theory relates to the questions about the nature of agency and I will also discuss my published theory on the physical nature of subjective experience and its relation to the brain, and how that theory interacts with Dual-Brain Psychology, leading to further insights into our human nature and its betterment.","PeriodicalId":74294,"journal":{"name":"NeuroSci","volume":"84 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73290973","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. Chan, Yvonne M. Y. Han, S. L. Sze, C. Wong, I. Chu, M. Cheung
Given the association between deviated inflammatory chemokines, the pathogenesis of autism spectrum disorders (ASD), and our previous findings of the Chanwuyi Lifestyle Medicine Program regarding improved cognitive and behavioral problems in ASD, the present study aims to explore if this intervention can alter pro-inflammatory chemokines concentration. Thirty-two boys with ASD were assigned to the experimental group receiving the Chanwuyi Lifestyle Medicine Program for 7 months or the control group without a change in their lifestyle. The experimental group, but not the control group, demonstrated significantly reduced CCL2 and CXCL8, a trend of reduction in CCL5, and elevation of CXCL9. The experimental group also demonstrated significantly reduced social communication problems, repetitive/stereotypic behaviors, and hyperactive behaviors. The present findings support the potential efficacy and applicability of the Chanwuyi Lifestyle Medicine Program for reducing both behavioral problems and immunological dysfunction in ASD. Further studies are warranted to verify its treatment effect and its association with brain functions.
鉴于炎性趋化因子偏离与自闭症谱系障碍(ASD)发病机制之间的关联，以及我们之前在Chanwuyi生活方式医学项目中发现的改善ASD认知和行为问题的结果，本研究旨在探讨这种干预是否可以改变促炎性趋化因子的浓度。将32名ASD男孩分为实验组和对照组，实验组接受“Chanwuyi Lifestyle Medicine Program”治疗7个月，对照组不改变生活方式。实验组CCL2和CXCL8明显降低，CCL5有降低的趋势，CXCL9有升高的趋势，而对照组没有。实验组的社会沟通问题、重复/刻板行为和过度活跃行为也显著减少。本研究结果支持Chanwuyi Lifestyle Medicine Program在减少ASD的行为问题和免疫功能障碍方面的潜在功效和适用性。需要进一步的研究来验证其治疗效果及其与脑功能的关系。
{"title":"Chanwuyi Lifestyle Medicine Program Alleviates Immunological Deviation and Improves Behaviors in Autism","authors":"A. Chan, Yvonne M. Y. Han, S. L. Sze, C. Wong, I. Chu, M. Cheung","doi":"10.3390/NEUROSCI2020015","DOIUrl":"https://doi.org/10.3390/NEUROSCI2020015","url":null,"abstract":"Given the association between deviated inflammatory chemokines, the pathogenesis of autism spectrum disorders (ASD), and our previous findings of the Chanwuyi Lifestyle Medicine Program regarding improved cognitive and behavioral problems in ASD, the present study aims to explore if this intervention can alter pro-inflammatory chemokines concentration. Thirty-two boys with ASD were assigned to the experimental group receiving the Chanwuyi Lifestyle Medicine Program for 7 months or the control group without a change in their lifestyle. The experimental group, but not the control group, demonstrated significantly reduced CCL2 and CXCL8, a trend of reduction in CCL5, and elevation of CXCL9. The experimental group also demonstrated significantly reduced social communication problems, repetitive/stereotypic behaviors, and hyperactive behaviors. The present findings support the potential efficacy and applicability of the Chanwuyi Lifestyle Medicine Program for reducing both behavioral problems and immunological dysfunction in ASD. Further studies are warranted to verify its treatment effect and its association with brain functions.","PeriodicalId":74294,"journal":{"name":"NeuroSci","volume":"1 3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85290600","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}
Natalia Sánchez, Montserrat Olivares-Costa, Marcela P. González, R. Munita, Angelica P. Escobar, Rodrigo C. Meza, Mauricio Herrera-Rojas, Jessica Albornoz, Gianluca Merello, M. Andrés
Null mice for the dopamine D2 receptor (D2R) have been instrumental in understanding the function of this protein. For our research, we obtained the functional D2R knockout mouse strain described initially in 1997. Surprisingly, our biochemical characterization showed that this mouse strain is not a true knockout. We determined by sequence analysis of the rapid 3′ amplification of cDNA ends that functional D2R knockout mice express transcripts that lack only the eighth exon. Furthermore, immunofluorescence assays showed a D2R-like protein in the brain of functional D2R knockout mice. We verified by immunofluorescence that the recombinant truncated D2R is expressed in HEK293T cells, showing intracellular localization, colocalizing in the Golgi apparatus and the endoplasmic reticulum, but with less presence in the Golgi apparatus compared to the native D2R. As previously reported, functional D2R knockout mice are hypoactive and insensitive to the D2R agonist quinpirole. Concordantly, microdialysis studies confirmed that functional D2R knockout mice have lower extracellular dopamine levels in the striatum than the native mice. In conclusion, functional D2R knockout mice express transcripts that lead to a truncated D2R protein lacking from the sixth transmembrane domain to the C-terminus. We share these findings to avoid future confusion and the community considers this mouse strain in D2R traffic and protein–protein interaction studies.
{"title":"Knockout or Knock-in? A Truncated D2 Receptor Protein Is Expressed in the Brain of Functional D2 Receptor Knockout Mice","authors":"Natalia Sánchez, Montserrat Olivares-Costa, Marcela P. González, R. Munita, Angelica P. Escobar, Rodrigo C. Meza, Mauricio Herrera-Rojas, Jessica Albornoz, Gianluca Merello, M. Andrés","doi":"10.3390/NEUROSCI2020014","DOIUrl":"https://doi.org/10.3390/NEUROSCI2020014","url":null,"abstract":"Null mice for the dopamine D2 receptor (D2R) have been instrumental in understanding the function of this protein. For our research, we obtained the functional D2R knockout mouse strain described initially in 1997. Surprisingly, our biochemical characterization showed that this mouse strain is not a true knockout. We determined by sequence analysis of the rapid 3′ amplification of cDNA ends that functional D2R knockout mice express transcripts that lack only the eighth exon. Furthermore, immunofluorescence assays showed a D2R-like protein in the brain of functional D2R knockout mice. We verified by immunofluorescence that the recombinant truncated D2R is expressed in HEK293T cells, showing intracellular localization, colocalizing in the Golgi apparatus and the endoplasmic reticulum, but with less presence in the Golgi apparatus compared to the native D2R. As previously reported, functional D2R knockout mice are hypoactive and insensitive to the D2R agonist quinpirole. Concordantly, microdialysis studies confirmed that functional D2R knockout mice have lower extracellular dopamine levels in the striatum than the native mice. In conclusion, functional D2R knockout mice express transcripts that lead to a truncated D2R protein lacking from the sixth transmembrane domain to the C-terminus. We share these findings to avoid future confusion and the community considers this mouse strain in D2R traffic and protein–protein interaction studies.","PeriodicalId":74294,"journal":{"name":"NeuroSci","volume":"197 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79925233","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}
C. Pickens, M. Gallo, Hayley Fisher, Alisa Pajser, Madelyn H. Ray
Reversal learning tasks are used to model flexible decision-making in laboratory animals, and exposure to drugs of abuse can cause long-term impairments in reversal learning. However, the long-term effects of alcohol on reversal learning have varied. We evaluated whether six weeks of voluntary alcohol consumption through chronic intermittent alcohol access (elevated by food restriction) in adult male rats would impair rats in a go/no-go reversal learning task when tested at an interval beyond acute withdrawal. In our go/no-go task, rats were reinforced for pressing one lever or withholding from pressing another lever, and the identities of the two levers were switched twice (once rats reached an accuracy criterion). We found no evidence that prior alcohol consumption altered discrimination or reversal learning in our task. This replicates previous patterns from our laboratory that higher alcohol consumption in food-restricted rats did not impair discrimination or reversal learning in a different go/no-go task and that alcohol consumption in free-fed adolescent/early adult rats did not impair go/no-go discrimination or reversal learning in the same task. It is unclear whether this represents an insensitivity of this task to alcohol exposure generally or whether an alcohol exposure procedure that leads to higher blood ethanol concentration (BEC) levels would impair learning. More research is needed to investigate these possibilities.
{"title":"Alcohol Consumption during Adulthood Does Not Impair Later Go/No-Go Reversal Learning in Male Rats","authors":"C. Pickens, M. Gallo, Hayley Fisher, Alisa Pajser, Madelyn H. Ray","doi":"10.3390/NEUROSCI2020012","DOIUrl":"https://doi.org/10.3390/NEUROSCI2020012","url":null,"abstract":"Reversal learning tasks are used to model flexible decision-making in laboratory animals, and exposure to drugs of abuse can cause long-term impairments in reversal learning. However, the long-term effects of alcohol on reversal learning have varied. We evaluated whether six weeks of voluntary alcohol consumption through chronic intermittent alcohol access (elevated by food restriction) in adult male rats would impair rats in a go/no-go reversal learning task when tested at an interval beyond acute withdrawal. In our go/no-go task, rats were reinforced for pressing one lever or withholding from pressing another lever, and the identities of the two levers were switched twice (once rats reached an accuracy criterion). We found no evidence that prior alcohol consumption altered discrimination or reversal learning in our task. This replicates previous patterns from our laboratory that higher alcohol consumption in food-restricted rats did not impair discrimination or reversal learning in a different go/no-go task and that alcohol consumption in free-fed adolescent/early adult rats did not impair go/no-go discrimination or reversal learning in the same task. It is unclear whether this represents an insensitivity of this task to alcohol exposure generally or whether an alcohol exposure procedure that leads to higher blood ethanol concentration (BEC) levels would impair learning. More research is needed to investigate these possibilities.","PeriodicalId":74294,"journal":{"name":"NeuroSci","volume":"72 1","pages":"166-176"},"PeriodicalIF":0.0,"publicationDate":"2021-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86909640","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}
Cognition is often defined as a dual process of physical and non-physical mechanisms. This duality originated from past theory on the constituent parts of the natural world. Even though material causation is not an explanation for all natural processes, phenomena at the cellular level of life are modeled by physical causes. These phenomena include explanations for the function of organ systems, including the nervous system and information processing in the cerebrum. This review restricts the definition of cognition to a mechanistic process and enlists studies that support an abstract set of proximate mechanisms. Specifically, this process is approached from a large-scale perspective, the flow of information in a neural system. Study at this scale further constrains the possible explanations for cognition since the information flow is amenable to theory, unlike a lower-level approach where the problem becomes intractable. These possible hypotheses include stochastic processes for explaining the processes of cognition along with principles that support an abstract format for the encoded information.
{"title":"Cognition as a Mechanical Process","authors":"R. Friedman","doi":"10.3390/NEUROSCI2020010","DOIUrl":"https://doi.org/10.3390/NEUROSCI2020010","url":null,"abstract":"Cognition is often defined as a dual process of physical and non-physical mechanisms. This duality originated from past theory on the constituent parts of the natural world. Even though material causation is not an explanation for all natural processes, phenomena at the cellular level of life are modeled by physical causes. These phenomena include explanations for the function of organ systems, including the nervous system and information processing in the cerebrum. This review restricts the definition of cognition to a mechanistic process and enlists studies that support an abstract set of proximate mechanisms. Specifically, this process is approached from a large-scale perspective, the flow of information in a neural system. Study at this scale further constrains the possible explanations for cognition since the information flow is amenable to theory, unlike a lower-level approach where the problem becomes intractable. These possible hypotheses include stochastic processes for explaining the processes of cognition along with principles that support an abstract format for the encoded information.","PeriodicalId":74294,"journal":{"name":"NeuroSci","volume":"239 1","pages":"141-150"},"PeriodicalIF":0.0,"publicationDate":"2021-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80436392","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}
Cigarette smoke (CS) has been consistently demonstrated to be an environmental risk factor for amyotrophic lateral sclerosis (ALS), although the molecular pathogenic mechanisms involved are yet to be elucidated. Here, we propose different mechanisms by which CS exposure can cause sporadic ALS pathogenesis. Oxidative stress and neuroinflammation are widely implicated in ALS pathogenesis, with blood–spinal cord barrier disruption also recognised to be involved in the disease process. In addition, immunometabolic, epigenetic and microbiome alterations have been implicated in ALS recently. Identification of the underlying pathophysiological mechanisms that underpin CS-associated ALS will drive future research to be conducted into new targets for treatment.
{"title":"Pathophysiological Correlation between Cigarette Smoking and Amyotrophic Lateral Sclerosis","authors":"Spiro Menounos, P. Hansbro, A. Diwan, Abhirup Das","doi":"10.3390/NEUROSCI2020008","DOIUrl":"https://doi.org/10.3390/NEUROSCI2020008","url":null,"abstract":"Cigarette smoke (CS) has been consistently demonstrated to be an environmental risk factor for amyotrophic lateral sclerosis (ALS), although the molecular pathogenic mechanisms involved are yet to be elucidated. Here, we propose different mechanisms by which CS exposure can cause sporadic ALS pathogenesis. Oxidative stress and neuroinflammation are widely implicated in ALS pathogenesis, with blood–spinal cord barrier disruption also recognised to be involved in the disease process. In addition, immunometabolic, epigenetic and microbiome alterations have been implicated in ALS recently. Identification of the underlying pathophysiological mechanisms that underpin CS-associated ALS will drive future research to be conducted into new targets for treatment.","PeriodicalId":74294,"journal":{"name":"NeuroSci","volume":"30 1","pages":"120-134"},"PeriodicalIF":0.0,"publicationDate":"2021-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74307666","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 article describes the practical use of Unity technology in neurogaming. For this purpose, the article describes Unity technology and brain–computer interface (BCI) technology based on the Emotiv EPOC + NeuroHeadset device. The process of creating the game world and the test results for the use of a device based on the BCI as a control interface for the created game are also presented. The game was created in the Unity graphics engine and the Visual Studio environment in C#. The game presented in the article is called “NeuroBall” due to the player’s object, which is a big red ball. The game will require full focus to make the ball move. The game will aim to improve the concentration and training of the user’s brain in a user-friendly environment. Through neurogaming, it will be possible to exercise and train a healthy brain, as well as diagnose and treat various symptoms of brain disorders. The project was entirely created in the Unity graphics engine in Unity version 2020.1.
本文描述了Unity技术在神经游戏中的实际应用。为此，本文介绍了基于Emotiv EPOC + NeuroHeadset设备的Unity技术和脑机接口(BCI)技术。本文还介绍了游戏世界的创建过程以及使用基于BCI的设备作为所创建游戏的控制接口的测试结果。这款游戏是在Unity图像引擎和Visual Studio c#环境中创建的。这款游戏之所以被称为“NeuroBall”，是因为玩家的目标是一个大红球。这场比赛需要全神贯注才能使球移动。这款游戏的目标是在一个用户友好的环境中提高注意力和训练用户的大脑。通过神经游戏，将有可能锻炼和训练健康的大脑，以及诊断和治疗大脑疾病的各种症状。该项目完全是在Unity版本2020.1的Unity图形引擎中创建的。
{"title":"A Pilot Study of Game Design in the Unity Environment as an Example of the Use of Neurogaming on the Basis of Brain–Computer Interface Technology to Improve Concentration","authors":"S. Paszkiel, R. Rojek, Ningrong Lei, M. A. Castro","doi":"10.3390/NEUROSCI2020007","DOIUrl":"https://doi.org/10.3390/NEUROSCI2020007","url":null,"abstract":"The article describes the practical use of Unity technology in neurogaming. For this purpose, the article describes Unity technology and brain–computer interface (BCI) technology based on the Emotiv EPOC + NeuroHeadset device. The process of creating the game world and the test results for the use of a device based on the BCI as a control interface for the created game are also presented. The game was created in the Unity graphics engine and the Visual Studio environment in C#. The game presented in the article is called “NeuroBall” due to the player’s object, which is a big red ball. The game will require full focus to make the ball move. The game will aim to improve the concentration and training of the user’s brain in a user-friendly environment. Through neurogaming, it will be possible to exercise and train a healthy brain, as well as diagnose and treat various symptoms of brain disorders. The project was entirely created in the Unity graphics engine in Unity version 2020.1.","PeriodicalId":74294,"journal":{"name":"NeuroSci","volume":"102 1","pages":"109-119"},"PeriodicalIF":0.0,"publicationDate":"2021-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77524821","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}
Nurfarhanah Bte Syed Sulaiman, C. Kuick, K. Chang, Kai Rui Wan, W. S. Looi, D. Low, W. Seow, S. Low
Pilocytic astrocytomas (PCA) are WHO Grade I tumors with a favorable prognosis. Surgical resection is usually curative. Nonetheless, progressive and/or metastatic disease occurs in 20% of patients. For these patients, treatment options are limited. The role of the immune system in PCA has not previously been reported. We hypothesize that the circulating cytokines contribute to tumorigenicity in PCA. This is an exploratory study with a focus on the identification of circulating cerebrospinal (CSF) cytokines associated with PCA. The primary objective is to demonstrate that CSF cytokines will be differentially expressed in the subset of PCAs that are difficult to treat in comparison to their surgically amendable counterparts. This is a single-institution, retrospective study of prospectively collected data. Patients with a confirmed histological diagnosis of PCA who have simultaneous intraoperative CSF sampling are included. Cerebrospinal fluid samples are subjected to multiplex cytokine profiling. Patient-derived PCA lines from selected patients in the same study cohort are cultured. Their cell culture supernatants are collected and interrogated using the sample multiplex platform as the CSF. A total of 8 patients are recruited. There were two patients with surgically difficult tumors associated with leptomeningeal involvement. Multiplex profiling of the cohort’s CSF samples showed elevated expressions of IFN-γ, IL-2, IL-12p70, IL-1β, IL-4, and TNF-α in these two patients in comparison to the remaining cohort. Next, primary cell lines derived from the same PCA patients demonstrated a similar trend of differential cytokine expression in their cell culture supernatant in vitro. Although our findings are preliminary at this stage, this is the first study in pediatric PCAs that show cytokine expression differences between the two groups of PCA with different clinical behaviors.
{"title":"Cytokines in Pediatric Pilocytic Astrocytomas: A Clinico-Pathological Study","authors":"Nurfarhanah Bte Syed Sulaiman, C. Kuick, K. Chang, Kai Rui Wan, W. S. Looi, D. Low, W. Seow, S. Low","doi":"10.3390/NEUROSCI2010006","DOIUrl":"https://doi.org/10.3390/NEUROSCI2010006","url":null,"abstract":"Pilocytic astrocytomas (PCA) are WHO Grade I tumors with a favorable prognosis. Surgical resection is usually curative. Nonetheless, progressive and/or metastatic disease occurs in 20% of patients. For these patients, treatment options are limited. The role of the immune system in PCA has not previously been reported. We hypothesize that the circulating cytokines contribute to tumorigenicity in PCA. This is an exploratory study with a focus on the identification of circulating cerebrospinal (CSF) cytokines associated with PCA. The primary objective is to demonstrate that CSF cytokines will be differentially expressed in the subset of PCAs that are difficult to treat in comparison to their surgically amendable counterparts. This is a single-institution, retrospective study of prospectively collected data. Patients with a confirmed histological diagnosis of PCA who have simultaneous intraoperative CSF sampling are included. Cerebrospinal fluid samples are subjected to multiplex cytokine profiling. Patient-derived PCA lines from selected patients in the same study cohort are cultured. Their cell culture supernatants are collected and interrogated using the sample multiplex platform as the CSF. A total of 8 patients are recruited. There were two patients with surgically difficult tumors associated with leptomeningeal involvement. Multiplex profiling of the cohort’s CSF samples showed elevated expressions of IFN-γ, IL-2, IL-12p70, IL-1β, IL-4, and TNF-α in these two patients in comparison to the remaining cohort. Next, primary cell lines derived from the same PCA patients demonstrated a similar trend of differential cytokine expression in their cell culture supernatant in vitro. Although our findings are preliminary at this stage, this is the first study in pediatric PCAs that show cytokine expression differences between the two groups of PCA with different clinical behaviors.","PeriodicalId":74294,"journal":{"name":"NeuroSci","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74062470","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 : 2021-03-03DOI: 10.21203/RS.3.RS-260558/V1
Rafael Themoteo, Vanessa de Paula, Nikole Kimberly, H. Brentani, O. Forlenza
BackgroundThere is consistent evidence of the potential benefits of lithium attenuating mechanisms of neurodegeneration, including those related to the pathophysiology of Alzheimer’s disease (AD), and facilitating neurotrophic and protective responses, including maintenance of telomere length. The aim was to investigate the protective effect of the pre-treatment with lithium on amyloid-beta (Aβ)-induced toxicity and telomere length in neurons. MethodsCortical neurons were treated with lithium chloride at therapeutic and subtherapeutic concentrations (2mM, 0.2mM and 0.02mM) for seven days. Amyloid toxicity was induced 24 hours before the end of lithium treatment. ResultsLithium resulted in 120% (2mM), 180% (0.2mM) and 140% (0.02mM) increments in telomere length as compared to untreated controls. Incubation with Aβ1-42 was associated with significant reductions in MTT uptake (33%) and telomere length (83%) as compared to controls. ConclusionsLithium prevented loss of culture viability and telomere shortening in neuronal cultures challenged with Aβ fibrils.
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