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Martine Uittenbogaard, Christine A Brantner, Anne Chiaramello
During neural development, epigenetic modulation of chromatin acetylation is part of a dynamic, sequential and critical process to steer the fate of multipotent neural progenitors toward a specific lineage. Pan-HDAC inhibitors (HDCis) trigger neuronal differentiation by generating an "acetylation" signature and promoting the expression of neurogenic bHLH transcription factors. Our studies and others have revealed a link between neuronal differentiation and increase of mitochondrial mass. However, the neuronal regulation of mitochondrial biogenesis has remained largely unexplored...
March 2, 2018: Cell Death & Disease
Belal Shohayeb, Mohamed Diab, Mazen Ahmed, Dominic Chi Hiung Ng
Adult neurogenesis involves persistent proliferative neuroprogenitor populations that reside within distinct regions of the brain. This phenomenon was first described over 50 years ago and it is now firmly established that new neurons are continually generated in distinct regions of the adult brain. The potential of enhancing the neurogenic process lies in improved brain cognition and neuronal plasticity particularly in the context of neuronal injury and neurodegenerative disorders. In addition, adult neurogenesis might also play a role in mood and affective disorders...
2018: Translational Neurodegeneration
Francesca L'Episcopo, Cataldo Tirolo, Maria F Serapide, Salvatore Caniglia, Nunzio Testa, Loredana Leggio, Silvia Vivarelli, Nunzio Iraci, Stefano Pluchino, Bianca Marchetti
Neuroinflammatory processes are recognized key contributory factors in Parkinson's disease (PD) physiopathology. While the causes responsible for the progressive loss of midbrain dopaminergic (mDA) neuronal cell bodies in the subtantia nigra pars compacta are poorly understood, aging, genetics, environmental toxicity, and particularly inflammation, represent prominent etiological factors in PD development. Especially, reactive astrocytes, microglial cells, and infiltrating monocyte-derived macrophages play dual beneficial/harmful effects, via a panel of pro- or anti-inflammatory cytokines, chemokines, neurotrophic and neurogenic transcription factors...
2018: Frontiers in Aging Neuroscience
Mina Desai, Monica G Ferrini, Guang Han, Juanita K Jellyman, Michael G Ross
In utero exposure to the ubiquitous plasticizer, bisphenol A (BPA) is associated with offspring obesity. As food intake/appetite is one of the critical elements contributing to obesity, we determined the effects of in vivo maternal BPA and in vitro BPA exposure on newborn hypothalamic stem cells which form the arcuate nucleus appetite center. For in vivo studies, female rats received BPA prior to and during pregnancy via drinking water, and newborn offspring primary hypothalamic neuroprogenitor (NPCs) were obtained and cultured...
February 21, 2018: Environmental Research
Zubair Ahmed Nizamudeen, Lisa Chakrabarti, Virginie Sottile
Fasudil is a clinically approved Rho-associated protein kinase (ROCK) inhibitor that has been used widely to treat cerebral consequences of subarachnoid hemorrhage. It is known to have a positive effect on animal models of neurological disorders including Parkinson's disease and stroke. However, its cellular effect on progenitor populations and differentiation is not clearly understood. While recent studies suggest that fasudil promotes the mobilization of neural stem cells (NSCs) from the subventricular zone in vivo and promotes the differentiation of the C17...
February 6, 2018: Stem Cell Research
Dal Khatri, Genevieve Laroche, Marion L Grant, Victoria M Jones, Ryan P Vetreno, Fulton T Crews, Somnath Mukhopadhyay
BACKGROUND: Chronic ethanol exposure has been found to inhibit adult hippocampal neurogenesis in multiple models of alcohol addiction. However, acute ethanol inhibition of adult neurogenesis is not well studied. Although many abused drugs have been found to inhibit adult neurogenesis, few have studied cannabinoids or cannabinoids with ethanol, although human use of both together is becoming more common. We used an acute binge alcohol drinking model in combination with select cannabinoid receptor agonists and antagonists to investigate the actions of each alone and together on hippocampal neurogenesis...
February 8, 2018: Alcoholism, Clinical and Experimental Research
Clementina Cobolli Gigli, Linda Scaramuzza, Marco De Simone, Riccardo L Rossi, Davide Pozzi, Massimiliano Pagani, Nicoletta Landsberger, Francesco Bedogni
During differentiation, neurons progressively restrict their fate repressing the expression of specific genes. Here we describe the involvement in such developmental steps of the methyl-CpG binding protein 2 (MeCP2), an epigenetic factor that participates to chromatin folding and transcriptional regulation. We previously reported that, due to transcriptional impairments, the maturation of Mecp2 null neurons is delayed. To evaluate whether this could stem from altered progenitors proliferation and differentiation, we investigated whether lack of Mecp2 affects these features both in vitro and in vivo...
January 17, 2018: Cerebral Cortex
Bo Liu, Li-Hua Sun, Yan-Fei Huang, Li-Jun Guo, Li-Shu Luo
Protein phosphatase 2ACα (PP2ACα), a vital member of the protein phosphatase family, has been studied primarily as a regulator for the development, growth and protein synthesis of a lot of cell types. Dysfunction of PP2ACα protein results in neurodegenerative disease; however, this finding has not been directly confirmed in the mouse model with PP2ACα gene knock-out. Therefore, in this study presented here, we generated the PP2ACα gene knock-out mouse model by the Cre-loxP targeting gene system, with the purpose to directly observe the regulatory role of PP2ACα gene in the development of mouse's cerebral cortex...
December 20, 2017: International Journal of Biochemistry & Cell Biology
Pascaline Létard, Séverine Drunat, Yoann Vial, Sarah Duerinckx, Anais Ernault, Daniel Amram, Stéphanie Arpin, Marta Bertoli, Tiffany Busa, Berten Ceulemans, Julie Desir, Martine Doco-Fenzy, Siham Chafai Elalaoui, Koenraad Devriendt, Laurence Faivre, Christine Francannet, David Geneviève, Marion Gérard, Cyril Gitiaux, Sophie Julia, Sébastien Lebon, Toni Lubala, Michèle Mathieu-Dramard, Hélène Maurey, Julia Metreau, Sanaa Nasserereddine, Mathilde Nizon, Geneviève Pierquin, Nathalie Pouvreau, Clothilde Rivier-Ringenbach, Massimiliano Rossi, Elise Schaefer, Abdelaziz Sefiani, Sabine Sigaudy, Yves Sznajer, Yusuf Tunca, Sophie Guilmin Crepon, Corinne Alberti, Monique Elmaleh-Bergès, Brigitte Benzacken, Bernd Wollnick, C Geoffrey Woods, Anita Rauch, Marc Abramowicz, Vincent El Ghouzzi, Pierre Gressens, Alain Verloes, Sandrine Passemard
Autosomal recessive microcephaly or MicroCephaly Primary Hereditary (MCPH) is a genetically heterogeneous neurodevelopmental disorder characterized by a reduction in brain volume, indirectly measured by an occipitofrontal circumference (OFC) 2 standard deviations or more below the age- and sex-matched mean (-2SD) at birth and -3SD after 6 months, and leading to intellectual disability of variable severity. The Abnormal SPindle-like Microcephaly gene (ASPM), the human ortholog of the Drosophila melanogaster 'abnormal spindle' gene (asp), encodes ASPM, a protein localized at the centrosome of apical neuroprogenitor cells and involved in spindle pole positioning during neurogenesis...
December 14, 2017: Human Mutation
Lukasz P Slomnicki, Dong-Hoon Chung, Austin Parker, Taylor Hermann, Nolan L Boyd, Michal Hetman
We report here that in rat and human neuroprogenitor cells as well as rat embryonic cortical neurons Zika virus (ZIKV) infection leads to ribosomal stress that is characterized by structural disruption of the nucleolus. The anti-nucleolar effects were most pronounced in postmitotic neurons. Moreover, in the latter system, nucleolar presence of ZIKV capsid protein (ZIKV-C) was associated with ribosomal stress and apoptosis. Deletion of 22 C-terminal residues of ZIKV-C prevented nucleolar localization, ribosomal stress and apoptosis...
November 30, 2017: Scientific Reports
Sol Beccari, Jorge Valero, Mirjana Maletic-Savatic, Amanda Sierra
Adult hippocampal neuroprogenitors give rise to both neurons and astrocytes. As neuroprogenitors are lost with increased age, neurogenesis concomitantly decreases. However, the dynamics of neuron and astrocyte generation throughout adulthood has not been systematically examined. Here, we analyzed the hippocampal niche both longitudinally (from 2 h to 30d of cell life) and transversally (from 1 m to 12 m of age) and generated a Marsaglia polar random simulation model to predict newborn cell dynamics. The sharp decrease in newborn neuron production throughout adulthood was largely predicted by the number of proliferating neuroprogenitors at each age...
November 28, 2017: Scientific Reports
Ardeshir Moayeri, Maryam Nazm Bojnordi, Sara Haratizadeh, Amir Esmaeilnejad-Moghadam, Rafieh Alizadeh, Hatef Ghasemi Hamidabadi
Introduction: The nerve fibers in central nervous system are surrounded by myelin sheet which is formed by oligodendrocytes. Cell therapy based on oligodendrocytes and their precursors transplantation can hold a promising alternative treatment for myelin sheet repair in demyelinating diseases. Methods: Human Dental Pulp Stem Cells (hDPSCs) are noninvasive, autologous and easy available source with multipotency characteristics, so they are in focus of interest in regenerative medicine...
September 2017: Basic and Clinical Neuroscience
Xiaoqian Liu, Wen Zong, Tangliang Li, Yujun Wang, Xingzhi Xu, Zhong-Wei Zhou, Zhao-Qi Wang
Mutations of microcephalin (MCPH1) can cause the neurodevelopmental disorder primary microcephaly type 1. We previously showed that MCPH1 deletion in neural stem cells results in early mitotic entry that distracts cell division mode, leading to exhaustion of the progenitor pool. Here, we show that MCPH1 interacts with and promotes the E3 ligase βTrCP2 to degrade Cdc25A independent of DNA damage. Overexpression of βTrCP2 or the knockdown of Cdc25A remedies the high mitotic index and rescues the premature differentiation of Mcph1-deficient neuroprogenitors in vivo MCPH1 itself is degraded by APC/C(C)(dh1), but not APC/C(C)(dc20), in late mitosis and G1 phase...
November 17, 2017: EMBO Journal
Kuo-Jen Wu, Seongjin Yu, Jea-Young Lee, Barry Hoffer, Yun Wang
Stroke induces not only cell death but also neurorepair. De novo neurogenesis has been found in the subventricular zone of the adult mammalian brain days after stroke. Most of these newly generated cells die shortly after the insult. Recent studies have shown that pharmacological manipulation can improve the survival of endogenous neuroprogenitor cells and neural regeneration in stroke rats. As these drugs target the endogenous reparative processes that occur days after stroke, they may provide a prolonged window for stroke therapy...
September 2017: Cell Transplantation
Luodan Yang, Donovan Tucker, Yan Dong, Chongyun Wu, Yujiao Lu, Yong Li, Juan Zhang, Timon Cheng-Yi Liu, Quanguang Zhang
Recent work has indicated that photobiomodulation (PBM) may beneficially alter the pathological status of several neurological disorders, although the mechanism currently remains unclear. The current study was designed to investigate the beneficial effect of PBM on behavioral deficits and neurogenesis in a photothrombotic (PT) model of ischemic stroke in rats. From day 1 to day 7 after the establishment of PT model, 2-minute daily PBM (CW, 808nm, 350mW/cm2 , total 294J at scalp level) was applied on the infarct injury area (1...
January 2018: Experimental Neurology
Pradip Devhare, Keith Meyer, Robert Steele, Ratna B Ray, Ranjit Ray
The current outbreak of Zika virus-associated diseases in South America and its threat to spread to other parts of the world has emerged as a global health emergency. A strong link between Zika virus and microcephaly exists, and the potential mechanisms associated with microcephaly are under intense investigation. In this study, we evaluated the effect of Zika virus infection of Asian and African lineages (PRVABC59 and MR766) in human neural stem cells (hNSCs). These two Zika virus strains displayed distinct infection pattern and growth rates in hNSCs...
October 12, 2017: Cell Death & Disease
Rajendra Gharbaran, Latchman Somenarain
The recent upsurge in the association of congenital neurological disorders and infection by the Zika virus (ZIKV) has resulted in increased research focus on the biology of this flavivirus. Studies in animal models indicate that ZIKV can breach the placental barrier and selectively infect and deplete neuroprogenitor cells (NPCs) of the developing fetus, resulting in changes of brain structures, reminiscent of human microcephaly. In vitro and ex vivo studies using human cells and tissues showed that human NPCs and placental cells are targeted by ZIKV...
October 7, 2017: Pathology
Biao Li, Amanda Sierra, Juan Jose Deudero, Fatih Semerci, Andrew Laitman, Marek Kimmel, Mirjana Maletic-Savatic
BACKGROUND: Adult hippocampal neurogenesis, the process of formation of new neurons, occurs throughout life in the hippocampus. New neurons have been associated with learning and memory as well as mood control, and impaired neurogenesis has been linked to depression, schizophrenia, autism and cognitive decline during aging. Thus, understanding the biological properties of adult neurogenesis has important implications for human health. Computational models of neurogenesis have attempted to derive biologically relevant knowledge, hard to achieve using experimentation...
October 3, 2017: BMC Systems Biology
Huaibiao Li, Torsten Kroll, Jürgen Moll, Lucien Frappart, Peter Herrlich, Heike Heuer, Aspasia Ploubidou
Misoriented division of neuroprogenitors, by loss-of-function studies of centrosome or spindle components, has been linked to the developmental brain defects microcephaly and lissencephaly. As these approaches also affect centrosome biogenesis, spindle assembly, or cell-cycle progression, the resulting pathologies cannot be attributed solely to spindle misorientation. To address this issue, we employed a truncation of the spindle-orienting protein RHAMM. This truncation of the RHAMM centrosome-targeting domain does not have an impact on centrosome biogenesis or on spindle assembly in vivo...
October 10, 2017: Stem Cell Reports
Miles R Bryan, Aaron B Bowman
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease resulting in motor impairment and death in patients. Recently, several studies have demonstrated insulin or insulin-like growth factor (IGF) treatment in models of HD, resulting in potent amelioration of HD phenotypes via modulation of the PI3K/AKT/mTOR pathways. Administration of IGF and insulin can rescue microtubule transport, metabolic function, and autophagy defects, resulting in clearance of Huntingtin (HTT) aggregates, restoration of mitochondrial function, amelioration of motor abnormalities, and enhanced survival...
2017: Advances in Neurobiology
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