Pub Date : 2017-01-05eCollection Date: 2017-01-01DOI: 10.1080/23262133.2016.1256856
Eun Ji Song, Seong Gak Jeon, Kyoung Ah Kim, Jin-Il Kim, Minho Moon
Despite the effects of CD4+ T cell dysfunction on cognitive and behavioral impairment are well established, the effects of Th2 cytokines on the adult hippocampal neurogenesis and cognitive function in restricted CD4+ T cell receptor (TCR) repertoire model have not been fully elucidate. We found that mice with restricted CD4+ repertoire TCR showed decreased adult hippocampal neurogenesis using OT-II mice. Moreover, we demonstrated that OT-II mice showed increased Th2 cytokine levels in peripheral organs and IL-4 levels in brain. Taken together, altered Th2 cytokine levels may impact learning and memory via impaired adult neurogenesis in restricted CD4+ repertoire TCR mice.
{"title":"Restricted CD4+ T cell receptor repertoire impairs cognitive function via alteration of Th2 cytokine levels.","authors":"Eun Ji Song, Seong Gak Jeon, Kyoung Ah Kim, Jin-Il Kim, Minho Moon","doi":"10.1080/23262133.2016.1256856","DOIUrl":"https://doi.org/10.1080/23262133.2016.1256856","url":null,"abstract":"<p><p>Despite the effects of CD4+ T cell dysfunction on cognitive and behavioral impairment are well established, the effects of Th2 cytokines on the adult hippocampal neurogenesis and cognitive function in restricted CD4+ T cell receptor (TCR) repertoire model have not been fully elucidate. We found that mice with restricted CD4+ repertoire TCR showed decreased adult hippocampal neurogenesis using OT-II mice. Moreover, we demonstrated that OT-II mice showed increased Th2 cytokine levels in peripheral organs and IL-4 levels in brain. Taken together, altered Th2 cytokine levels may impact learning and memory via impaired adult neurogenesis in restricted CD4+ repertoire TCR mice.</p>","PeriodicalId":74274,"journal":{"name":"Neurogenesis (Austin, Tex.)","volume":"4 1","pages":"e1256856"},"PeriodicalIF":0.0,"publicationDate":"2017-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23262133.2016.1256856","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34757198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01DOI: 10.1080/23262133.2016.1270383
F. Stagni, A. Giacomini, M. Emili, S. Guidi, E. Ciani, R. Bartesaghi
ABSTRACT Neurodevelopmental alterations and cognitive disability are constant features of Down syndrome (DS), a genetic condition due to triplication of chromosome 21. DYRK1A is one of the triplicated genes that is thought to be strongly involved in brain alterations. Treatment of Dyrk1A transgenic mice with epigallocatechin gallate (EGCG), an inhibitor of DYRK1A, improves cognitive performance, suggesting that EGCG may represent a suitable treatment of DS. Evidence in the Ts65Dn mouse model of DS shows that EGCG restores hippocampal development, although this effect is ephemeral. Other studies, however, show no effects of treatment on hippocampus-dependent memory. On the other hand, a pilot study in young adults with DS shows that EGCG transiently improves some aspects of memory. Interestingly, EGCG plus cognitive training engenders effects that are more prolonged. Studies in various rodent models show a positive impact of EGCG on brain and behavior, but other studies show no effect. In spite of these discrepancies, possibly due to heterogeneity of protocols/timing/species, EGCG seems to exert some beneficial effects on the brain. It is possible that protocols of periodic EGCG administration to individuals with DS (alone or in conjunction with other treatments) may prevent the disappearance of its effects.
{"title":"Epigallocatechin gallate: A useful therapy for cognitive disability in Down syndrome?","authors":"F. Stagni, A. Giacomini, M. Emili, S. Guidi, E. Ciani, R. Bartesaghi","doi":"10.1080/23262133.2016.1270383","DOIUrl":"https://doi.org/10.1080/23262133.2016.1270383","url":null,"abstract":"ABSTRACT Neurodevelopmental alterations and cognitive disability are constant features of Down syndrome (DS), a genetic condition due to triplication of chromosome 21. DYRK1A is one of the triplicated genes that is thought to be strongly involved in brain alterations. Treatment of Dyrk1A transgenic mice with epigallocatechin gallate (EGCG), an inhibitor of DYRK1A, improves cognitive performance, suggesting that EGCG may represent a suitable treatment of DS. Evidence in the Ts65Dn mouse model of DS shows that EGCG restores hippocampal development, although this effect is ephemeral. Other studies, however, show no effects of treatment on hippocampus-dependent memory. On the other hand, a pilot study in young adults with DS shows that EGCG transiently improves some aspects of memory. Interestingly, EGCG plus cognitive training engenders effects that are more prolonged. Studies in various rodent models show a positive impact of EGCG on brain and behavior, but other studies show no effect. In spite of these discrepancies, possibly due to heterogeneity of protocols/timing/species, EGCG seems to exert some beneficial effects on the brain. It is possible that protocols of periodic EGCG administration to individuals with DS (alone or in conjunction with other treatments) may prevent the disappearance of its effects.","PeriodicalId":74274,"journal":{"name":"Neurogenesis (Austin, Tex.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23262133.2016.1270383","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44156551","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 : 2017-01-01DOI: 10.1080/23262133.2017.1324258
H. Hříbková, J. Zelinková, Yuh-Man Sun
ABSTRACT Human pluripotent stem cell (hPSC)-based modeling offers the potential for studying human diseases using human systems. An increasing number of studies in numerous fields demonstrate that hPSC-based disease systems capture disease specific pathophysiology occurring in vivo. A widespread deployment of hPSC systems is foreseeable. Even the field of psychiatric disorders (for example, schizophrenia and autism), which lags behind due to complex underlying causes, such as the inaccessibility of brain cells for assessments and the absence of reliable models, has been embracing the hPSC-based disease system. However, despite hPSCs holding great potential, it is imperative to validate how faithful hPSC-based neural developmental modeling is in recapitulating the developmental process in vivo. Our recent study demonstrated that the hPSC-based system mimicked the process of neural development and the system reserved neural stem cell (NSC) niches similar to those residing in the ventricular region of the cortex. In this article, we will first comment on an array of factors that affect hPSC-based neural differentiation and summarize the intricate regulatory signaling pathways that regionalize neuronal cell types. Finally, we review successful studies in brain-related diseases using hPSC-based modeling with 3-D systems.
{"title":"Progress in human pluripotent stem cell-based modeling systems for neurological diseases","authors":"H. Hříbková, J. Zelinková, Yuh-Man Sun","doi":"10.1080/23262133.2017.1324258","DOIUrl":"https://doi.org/10.1080/23262133.2017.1324258","url":null,"abstract":"ABSTRACT Human pluripotent stem cell (hPSC)-based modeling offers the potential for studying human diseases using human systems. An increasing number of studies in numerous fields demonstrate that hPSC-based disease systems capture disease specific pathophysiology occurring in vivo. A widespread deployment of hPSC systems is foreseeable. Even the field of psychiatric disorders (for example, schizophrenia and autism), which lags behind due to complex underlying causes, such as the inaccessibility of brain cells for assessments and the absence of reliable models, has been embracing the hPSC-based disease system. However, despite hPSCs holding great potential, it is imperative to validate how faithful hPSC-based neural developmental modeling is in recapitulating the developmental process in vivo. Our recent study demonstrated that the hPSC-based system mimicked the process of neural development and the system reserved neural stem cell (NSC) niches similar to those residing in the ventricular region of the cortex. In this article, we will first comment on an array of factors that affect hPSC-based neural differentiation and summarize the intricate regulatory signaling pathways that regionalize neuronal cell types. Finally, we review successful studies in brain-related diseases using hPSC-based modeling with 3-D systems.","PeriodicalId":74274,"journal":{"name":"Neurogenesis (Austin, Tex.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23262133.2017.1324258","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45953921","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 : 2017-01-01DOI: 10.1080/23262133.2017.1329683
Francisca F. Vasconcelos, D. Castro
ABSTRACT The generation of neurons at the correct time and location in the developing nervous system requires a fine balance between gene expression programs that regulate differentiation and maintenance of neural stem cells. During vertebrate neurogenesis, cell fate commitment and differentiation of neural stem cells toward the neuronal lineage are regulated by the opposing activities of the proneural and Notch pathways. Neuronal differentiation is inhibited by high Notch signaling characteristic of neural stem/progenitor cells, and requires the repression of the Notch transcriptional program by mechanisms that are still poorly understood. In a recent study1, we showed the zinc-finger transcription factor MyT1 promotes neurogenesis downstream the proneural factor Ascl1. MyT1 functions as a repressor of many Notch transcriptional target genes, linking the activation of a differentiation program by Ascl1 with the repression of the neural progenitor identity. Here we analyze our findings in light of the current knowledge in the field, and discuss the implications to our understanding of how MyT1 family members operate in vertebrate neurogenesis.
{"title":"Coordinating neuronal differentiation with repression of the progenitor program: Role of the transcription factor MyT1","authors":"Francisca F. Vasconcelos, D. Castro","doi":"10.1080/23262133.2017.1329683","DOIUrl":"https://doi.org/10.1080/23262133.2017.1329683","url":null,"abstract":"ABSTRACT The generation of neurons at the correct time and location in the developing nervous system requires a fine balance between gene expression programs that regulate differentiation and maintenance of neural stem cells. During vertebrate neurogenesis, cell fate commitment and differentiation of neural stem cells toward the neuronal lineage are regulated by the opposing activities of the proneural and Notch pathways. Neuronal differentiation is inhibited by high Notch signaling characteristic of neural stem/progenitor cells, and requires the repression of the Notch transcriptional program by mechanisms that are still poorly understood. In a recent study1, we showed the zinc-finger transcription factor MyT1 promotes neurogenesis downstream the proneural factor Ascl1. MyT1 functions as a repressor of many Notch transcriptional target genes, linking the activation of a differentiation program by Ascl1 with the repression of the neural progenitor identity. Here we analyze our findings in light of the current knowledge in the field, and discuss the implications to our understanding of how MyT1 family members operate in vertebrate neurogenesis.","PeriodicalId":74274,"journal":{"name":"Neurogenesis (Austin, Tex.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23262133.2017.1329683","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46426124","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 : 2017-01-01DOI: 10.1080/23262133.2016.1271495
Bastian G Brinkmann, Susanne Quintes
ABSTRACT Development of Schwann cells is tightly regulated by concerted action of activating and inhibiting factors. Most of the regulatory feedback loops identified to date are transcriptional activators promoting induction of genes coding for integral myelin proteins and lipids. The mechanisms by which inhibitory factors are silenced during Schwann cell maturation are less well understood. We could recently show a pivotal function for the transcription factor zinc finger E-box binding homeobox 2 (Zeb2) during Schwann cell development and myelination as a transcriptional repressor of maturation inhibitors. Zeb2 belongs to a family of highly conserved 2-handed zinc-finger proteins and represses gene transcription by binding to E-box sequences in the regulatory region of target genes. The protein is known to repress E-cadherin during epithelial to mesenchymal transition (EMT) in tumor malignancy and mediates its functions by interacting with multiple co-factors. During nervous system development, Zeb2 is expressed in neural crest cells, the precursors of Schwann cells, the myelinating glial cells of peripheral nerves. Schwann cells lacking Zeb2 fail to fully differentiate and are unable to sort and myelinate peripheral nerve axons. The maturation inhibitors Sox2, Ednrb and Hey2 emerge as targets for Zeb2-mediated transcriptional repression and show persistent aberrant expression in Zeb2-deficient Schwann cells. While dispensible for adult Schwann cells, re-activation of Zeb2 is essential after nerve injury to allow remyelination and functional recovery. In summary, Zeb2 emerges as an “inhibitor of inhibitors,” a novel concept in Schwann cell development and nerve repair.
{"title":"Zeb2: Inhibiting the inhibitors in Schwann cells","authors":"Bastian G Brinkmann, Susanne Quintes","doi":"10.1080/23262133.2016.1271495","DOIUrl":"https://doi.org/10.1080/23262133.2016.1271495","url":null,"abstract":"ABSTRACT Development of Schwann cells is tightly regulated by concerted action of activating and inhibiting factors. Most of the regulatory feedback loops identified to date are transcriptional activators promoting induction of genes coding for integral myelin proteins and lipids. The mechanisms by which inhibitory factors are silenced during Schwann cell maturation are less well understood. We could recently show a pivotal function for the transcription factor zinc finger E-box binding homeobox 2 (Zeb2) during Schwann cell development and myelination as a transcriptional repressor of maturation inhibitors. Zeb2 belongs to a family of highly conserved 2-handed zinc-finger proteins and represses gene transcription by binding to E-box sequences in the regulatory region of target genes. The protein is known to repress E-cadherin during epithelial to mesenchymal transition (EMT) in tumor malignancy and mediates its functions by interacting with multiple co-factors. During nervous system development, Zeb2 is expressed in neural crest cells, the precursors of Schwann cells, the myelinating glial cells of peripheral nerves. Schwann cells lacking Zeb2 fail to fully differentiate and are unable to sort and myelinate peripheral nerve axons. The maturation inhibitors Sox2, Ednrb and Hey2 emerge as targets for Zeb2-mediated transcriptional repression and show persistent aberrant expression in Zeb2-deficient Schwann cells. While dispensible for adult Schwann cells, re-activation of Zeb2 is essential after nerve injury to allow remyelination and functional recovery. In summary, Zeb2 emerges as an “inhibitor of inhibitors,” a novel concept in Schwann cell development and nerve repair.","PeriodicalId":74274,"journal":{"name":"Neurogenesis (Austin, Tex.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23262133.2016.1271495","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42680572","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 : 2017-01-01DOI: 10.1080/23262133.2017.1324259
K. Boschen, A. Klintsova
ABSTRACT Exposure of the embryo and fetus to alcohol can lead to abnormal physical, neuroanatomical, and behavioral development, collectively known as Fetal Alcohol Spectrum Disorders (FASDs). This mini-review focuses on the negative impact of prenatal alcohol exposure on hippocampal adult neurogenesis, an important process by which the brain adds new neurons throughout the lifespan, and hippocampal dendritic complexity through the discussion of various mammalian models of FASDs. Alcohol-induced aberrations in the outgrowth, phenotype, and stability of dendrites of neurons in the hippocampus and the prefrontal cortex will also be discussed. Timing of alcohol exposure during development (first trimester vs. third trimester-equivalent) can determine whether cell proliferation or long-term cell survival is impaired. Our work demonstrating that third trimester-equivalent exposure has a more significant impact on cell survival and dendritic morphology than rate of cell proliferation. Understanding the impact of prenatal ethanol exposure on adult neurogenesis is important as altered rates of new cell generation or successful integration of adult-born neurons could contribute to many of the hippocampal-associated deficits in memory and cognitive function observed in patients with FASDs. In addition, this commentary discusses evidence in support of aerobic exercise and environmental complexity (“enrichment”) as potential therapeutic strategies for alcohol-related deficits.
{"title":"Disruptions to hippocampal adult neurogenesis in rodent models of fetal alcohol spectrum disorders","authors":"K. Boschen, A. Klintsova","doi":"10.1080/23262133.2017.1324259","DOIUrl":"https://doi.org/10.1080/23262133.2017.1324259","url":null,"abstract":"ABSTRACT Exposure of the embryo and fetus to alcohol can lead to abnormal physical, neuroanatomical, and behavioral development, collectively known as Fetal Alcohol Spectrum Disorders (FASDs). This mini-review focuses on the negative impact of prenatal alcohol exposure on hippocampal adult neurogenesis, an important process by which the brain adds new neurons throughout the lifespan, and hippocampal dendritic complexity through the discussion of various mammalian models of FASDs. Alcohol-induced aberrations in the outgrowth, phenotype, and stability of dendrites of neurons in the hippocampus and the prefrontal cortex will also be discussed. Timing of alcohol exposure during development (first trimester vs. third trimester-equivalent) can determine whether cell proliferation or long-term cell survival is impaired. Our work demonstrating that third trimester-equivalent exposure has a more significant impact on cell survival and dendritic morphology than rate of cell proliferation. Understanding the impact of prenatal ethanol exposure on adult neurogenesis is important as altered rates of new cell generation or successful integration of adult-born neurons could contribute to many of the hippocampal-associated deficits in memory and cognitive function observed in patients with FASDs. In addition, this commentary discusses evidence in support of aerobic exercise and environmental complexity (“enrichment”) as potential therapeutic strategies for alcohol-related deficits.","PeriodicalId":74274,"journal":{"name":"Neurogenesis (Austin, Tex.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23262133.2017.1324259","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45317582","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 : 2017-01-01DOI: 10.1080/23262133.2016.1270384
B. Bardoni, M. Capovilla, E. Lalli
ABSTRACT FMRP is an RNA-binding protein involved in synaptic translation. Its absence causes a form of intellectual disability, the Fragile X syndrome (FXS). Small neuroanatomical abnormalities, present both in human and mouse FMRP-deficient brains, suggest a subtle critical role of this protein in neurogenesis. Stable depletion of FMRP has been obtained in a mouse embryonic stem cell line Fmr1 (shFmr1 ES) that does not display morphological alterations, but an abnormal expression of a subset of genes mainly involved in neuronal differentiation and maturation. Inducing the differentiation of shFmr1 ES cells into the neuronal lineage results in an accelerated generation of neural progenitors and neurons during the first steps of neurogenesis. This transient phenotype is due to an elevated level of the Amyloid Precursor Protein (APP), whose mRNA is a target of FMRP. APP is processed by the BACE-1 enzyme, producing the β-amyloid (Aβ) peptide accelerating neurogenesis by activating the expression of Ascll. Inhibition of the BACE-1 enzyme rescues the phenotype of shFmr1 ES cells. Here we discuss the importance of the shFmr1 ES line not only to understand the physiopathology of FXS but also as a tool to screen biomolecules for new FXS therapies.
{"title":"Modeling Fragile X syndrome in neurogenesis: An unexpected phenotype and a novel tool for future therapies","authors":"B. Bardoni, M. Capovilla, E. Lalli","doi":"10.1080/23262133.2016.1270384","DOIUrl":"https://doi.org/10.1080/23262133.2016.1270384","url":null,"abstract":"ABSTRACT FMRP is an RNA-binding protein involved in synaptic translation. Its absence causes a form of intellectual disability, the Fragile X syndrome (FXS). Small neuroanatomical abnormalities, present both in human and mouse FMRP-deficient brains, suggest a subtle critical role of this protein in neurogenesis. Stable depletion of FMRP has been obtained in a mouse embryonic stem cell line Fmr1 (shFmr1 ES) that does not display morphological alterations, but an abnormal expression of a subset of genes mainly involved in neuronal differentiation and maturation. Inducing the differentiation of shFmr1 ES cells into the neuronal lineage results in an accelerated generation of neural progenitors and neurons during the first steps of neurogenesis. This transient phenotype is due to an elevated level of the Amyloid Precursor Protein (APP), whose mRNA is a target of FMRP. APP is processed by the BACE-1 enzyme, producing the β-amyloid (Aβ) peptide accelerating neurogenesis by activating the expression of Ascll. Inhibition of the BACE-1 enzyme rescues the phenotype of shFmr1 ES cells. Here we discuss the importance of the shFmr1 ES line not only to understand the physiopathology of FXS but also as a tool to screen biomolecules for new FXS therapies.","PeriodicalId":74274,"journal":{"name":"Neurogenesis (Austin, Tex.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23262133.2016.1270384","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47752252","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 : 2017-01-01DOI: 10.1080/23262133.2016.1270381
Sarah Moyon, P. Casaccia
ABSTRACT Oligodendrocyte progenitor cells (OPC) are the myelinating cells of the central nervous system (CNS). During development, they differentiate into mature oligodendrocytes (OL) and ensheath axons, providing trophic and functional support to the neurons. This process is regulated by the dynamic expression of specific transcription factors, which, in turn, is controlled by epigenetic marks such as DNA methylation. Here we discuss recent findings showing that DNA methylation levels are differentially regulated in the oligodendrocyte lineage during developmental myelination, affecting both genes expression and alternative splicing events. Based on the phenotypic characterization of mice with genetic ablation of DNA methyltransferase 1 (Dnmt1) we conclude that DNA methylation is critical for efficient OPC expansion and for developmental myelination. Previous work suggests that in the context of diseases such as multiple sclerosis (MS) or gliomas, DNA methylation is differentially regulated in the CNS of affected individuals compared with healthy controls. In this commentary, based on the results of previous work, we propose the potential role of DNA methylation in adult oligodendroglial lineage cells in physiologic and pathological conditions, and delineate potential research approaches to be undertaken to test this hypothesis. A better understanding of this epigenetic modification in adult oligodendrocyte progenitor cells is essential, as it can potentially result in the design of new therapeutic strategies to enhance remyelination in MS patients or reduce proliferation in glioma patients.
{"title":"DNA methylation in oligodendroglial cells during developmental myelination and in disease","authors":"Sarah Moyon, P. Casaccia","doi":"10.1080/23262133.2016.1270381","DOIUrl":"https://doi.org/10.1080/23262133.2016.1270381","url":null,"abstract":"ABSTRACT Oligodendrocyte progenitor cells (OPC) are the myelinating cells of the central nervous system (CNS). During development, they differentiate into mature oligodendrocytes (OL) and ensheath axons, providing trophic and functional support to the neurons. This process is regulated by the dynamic expression of specific transcription factors, which, in turn, is controlled by epigenetic marks such as DNA methylation. Here we discuss recent findings showing that DNA methylation levels are differentially regulated in the oligodendrocyte lineage during developmental myelination, affecting both genes expression and alternative splicing events. Based on the phenotypic characterization of mice with genetic ablation of DNA methyltransferase 1 (Dnmt1) we conclude that DNA methylation is critical for efficient OPC expansion and for developmental myelination. Previous work suggests that in the context of diseases such as multiple sclerosis (MS) or gliomas, DNA methylation is differentially regulated in the CNS of affected individuals compared with healthy controls. In this commentary, based on the results of previous work, we propose the potential role of DNA methylation in adult oligodendroglial lineage cells in physiologic and pathological conditions, and delineate potential research approaches to be undertaken to test this hypothesis. A better understanding of this epigenetic modification in adult oligodendrocyte progenitor cells is essential, as it can potentially result in the design of new therapeutic strategies to enhance remyelination in MS patients or reduce proliferation in glioma patients.","PeriodicalId":74274,"journal":{"name":"Neurogenesis (Austin, Tex.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23262133.2016.1270381","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46610991","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 : 2016-12-27eCollection Date: 2016-01-01DOI: 10.1080/23262133.2016.1261653
Fu-Sheng Chou, Pei-Shan Wang
During development of the nervous system, radial glial cells perform self-renewing asymmetric divisions and give rise to intermediate progenitor cells (IPC) and neurons. The neuronally committed IPC subsequently undergo multiple rounds of transient amplification and migrate outwards to form cortical layers as they continue to differentiate into mature neurons. Maturing neurons extend protrusions on their cell surface to form neurites, a process called neuritogenesis. Neurite formation results in the establishment of dendrites and axons for synapse formation, which is essential for sensory and motor functions and even higher-level functioning including memory formation and cognitive function, as well as shaping of behavior and emotion. Morphological adaptation during various stages of neural development requires active participation of actin cytoskeleton remodeling. In this review, we aim to discuss current understanding of the Arp2/3 complex branching nucleator in various neural cell types during development and maturation.
{"title":"The Arp2/3 complex is essential at multiple stages of neural development.","authors":"Fu-Sheng Chou, Pei-Shan Wang","doi":"10.1080/23262133.2016.1261653","DOIUrl":"https://doi.org/10.1080/23262133.2016.1261653","url":null,"abstract":"<p><p>During development of the nervous system, radial glial cells perform self-renewing asymmetric divisions and give rise to intermediate progenitor cells (IPC) and neurons. The neuronally committed IPC subsequently undergo multiple rounds of transient amplification and migrate outwards to form cortical layers as they continue to differentiate into mature neurons. Maturing neurons extend protrusions on their cell surface to form neurites, a process called neuritogenesis. Neurite formation results in the establishment of dendrites and axons for synapse formation, which is essential for sensory and motor functions and even higher-level functioning including memory formation and cognitive function, as well as shaping of behavior and emotion. Morphological adaptation during various stages of neural development requires active participation of actin cytoskeleton remodeling. In this review, we aim to discuss current understanding of the Arp2/3 complex branching nucleator in various neural cell types during development and maturation.</p>","PeriodicalId":74274,"journal":{"name":"Neurogenesis (Austin, Tex.)","volume":"3 1","pages":"e1261653"},"PeriodicalIF":0.0,"publicationDate":"2016-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23262133.2016.1261653","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34909573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-12-20eCollection Date: 2017-01-01DOI: 10.1080/23262133.2016.1259709
Gustavo R Morel, Micaela López León, Maia Uriarte, Paula C Reggiani, Rodolfo G Goya
In rats, learning and memory performance decline during normal aging, which is paralleled by a severe reduction of the levels of neurogenesis in the hippocampal dentate gyrus (DG). A promising therapeutic strategy to restore neurogenesis in the hippocampus of old rats and their spatial memory involves the use of insulin-like growth factor-I (IGF-I). The peptide exerts pleiotropic effects in the brain, regulating multiple cellular processes. Thus, 4-week intracerebroventricular (ICV) perfusion of IGF-I significantly restored spatial memory and hippocampal neurogenesis in old male rats. Similar results were achieved by ICV IGF-I gene therapy in aging female rats. Thus, the treatment seemed to increase the number of immature neurons in the DG of 28 mo old rats, which was paralleled by an increase in the accuracy of the animals to remember specific patterns, which is known as pattern separation memory. The DG is thought to be the main hippocampal structure involved in pattern separation memory and there is evidence that the level of neurogenesis in the DG is directly related to pattern separation performance in rodents. Summing up, IGF-I emerges as a promising restorative molecule for increasing hippocampal neurogenesis and memory accuracy in aged individuals and possibly, in neurodegenerative pathologies.
在大鼠中，学习和记忆能力在正常衰老过程中下降，这与海马齿状回(DG)神经发生水平的严重减少是平行的。使用胰岛素样生长因子- i (IGF-I)是恢复老年大鼠海马神经发生及其空间记忆的一种有前景的治疗策略。该肽在大脑中发挥多效作用，调节多种细胞过程。因此，4周脑室灌流IGF-I可显著恢复老年雄性大鼠的空间记忆和海马神经发生。ICV igf - 1基因治疗衰老雌性大鼠也获得了类似的结果。因此，这种治疗似乎增加了28个月大鼠DG中未成熟神经元的数量，与此同时，动物记忆特定模式的准确性也有所提高，这被称为模式分离记忆。DG被认为是参与模式分离记忆的主要海马结构，有证据表明DG的神经发生水平与啮齿动物的模式分离表现直接相关。综上所述，igf - 1作为一种有希望的恢复分子，在老年人和可能的神经退行性疾病中增加海马神经发生和记忆准确性。
{"title":"Therapeutic potential of IGF-I on hippocampal neurogenesis and function during aging.","authors":"Gustavo R Morel, Micaela López León, Maia Uriarte, Paula C Reggiani, Rodolfo G Goya","doi":"10.1080/23262133.2016.1259709","DOIUrl":"https://doi.org/10.1080/23262133.2016.1259709","url":null,"abstract":"<p><p>In rats, learning and memory performance decline during normal aging, which is paralleled by a severe reduction of the levels of neurogenesis in the hippocampal dentate gyrus (DG). A promising therapeutic strategy to restore neurogenesis in the hippocampus of old rats and their spatial memory involves the use of insulin-like growth factor-I (IGF-I). The peptide exerts pleiotropic effects in the brain, regulating multiple cellular processes. Thus, 4-week intracerebroventricular (ICV) perfusion of IGF-I significantly restored spatial memory and hippocampal neurogenesis in old male rats. Similar results were achieved by ICV IGF-I gene therapy in aging female rats. Thus, the treatment seemed to increase the number of immature neurons in the DG of 28 mo old rats, which was paralleled by an increase in the accuracy of the animals to remember specific patterns, which is known as pattern separation memory. The DG is thought to be the main hippocampal structure involved in pattern separation memory and there is evidence that the level of neurogenesis in the DG is directly related to pattern separation performance in rodents. Summing up, IGF-I emerges as a promising restorative molecule for increasing hippocampal neurogenesis and memory accuracy in aged individuals and possibly, in neurodegenerative pathologies.</p>","PeriodicalId":74274,"journal":{"name":"Neurogenesis (Austin, Tex.)","volume":"4 1","pages":"e1259709"},"PeriodicalIF":0.0,"publicationDate":"2016-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23262133.2016.1259709","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34909574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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