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https://www.readbyqxmd.com/read/28805814/cerebellar-granule-cell-replenishment-postinjury-by-adaptive-reprogramming-of-nestin-progenitors
#1
Alexandre Wojcinski, Andrew K Lawton, N Sumru Bayin, Zhimin Lao, Daniel N Stephen, Alexandra L Joyner
Regeneration of several organs involves adaptive reprogramming of progenitors, but the intrinsic capacity of the developing brain to replenish lost cells remains largely unknown. Here we found that the developing cerebellum has unappreciated progenitor plasticity, since it undergoes near full growth and functional recovery following acute depletion of granule cells, the most plentiful neuron population in the brain. We demonstrate that following postnatal ablation of granule cell progenitors, Nestin-expressing progenitors, specified during mid-embryogenesis to produce astroglia and interneurons, switch their fate and generate granule neurons in mice...
August 14, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28760579/survival-of-ipsc-derived-grafts-within-the-striatum-of-immunodeficient-mice-importance-of-developmental-stage-of-both-transplant-and-host-recipient
#2
Colton M Tom, Shahab Younesi, Elana Meer, Catherine Bresee, Marlesa Godoy, Virginia B Mattis
Degeneration of the striatum can occur in multiple disorders with devastating consequences for the patients. Infantile infections with streptococcus, measles, or herpes can cause striatal necrosis associated with dystonia or dyskinesia; and in patients with Huntington's disease the striatum undergoes massive degeneration leading to behavioral, psychological and movement issues, ultimately resulting in death. Currently, only supportive therapies are available for striatal degeneration. Clinical trials have shown some efficacy using transplantation of fetal-derived primary striatal progenitors...
July 28, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28750583/association-of-a-history-of-child-abuse-with-impaired-myelination-in-the-anterior-cingulate-cortex-convergent-epigenetic-transcriptional-and-morphological-evidence
#3
Pierre-Eric Lutz, Arnaud Tanti, Alicja Gasecka, Sarah Barnett-Burns, John J Kim, Yi Zhou, Gang G Chen, Marina Wakid, Meghan Shaw, Daniel Almeida, Marc-Aurele Chay, Jennie Yang, Vanessa Larivière, Marie-Noël M'Boutchou, Léon C van Kempen, Volodymyr Yerko, Josée Prud'homme, Maria Antonietta Davoli, Kathryn Vaillancourt, Jean-François Théroux, Alexandre Bramoullé, Tie-Yuan Zhang, Michael J Meaney, Carl Ernst, Daniel Côté, Naguib Mechawar, Gustavo Turecki
OBJECTIVE: Child abuse has devastating and long-lasting consequences, considerably increasing the lifetime risk of negative mental health outcomes such as depression and suicide. Yet the neurobiological processes underlying this heightened vulnerability remain poorly understood. The authors investigated the hypothesis that epigenetic, transcriptomic, and cellular adaptations may occur in the anterior cingulate cortex as a function of child abuse. METHOD: Postmortem brain samples from human subjects (N=78) and from a rodent model of the impact of early-life environment (N=24) were analyzed...
July 28, 2017: American Journal of Psychiatry
https://www.readbyqxmd.com/read/28746305/stimulation-of-functional-neuronal-regeneration-from-m%C3%A3-ller-glia-in-adult-mice
#4
Nikolas L Jorstad, Matthew S Wilken, William N Grimes, Stefanie G Wohl, Leah S VandenBosch, Takeshi Yoshimatsu, Rachel O Wong, Fred Rieke, Thomas A Reh
Many retinal diseases lead to the loss of retinal neurons and cause visual impairment. The adult mammalian retina has little capacity for regeneration. By contrast, teleost fish functionally regenerate their retina following injury, and Müller glia (MG) are the source of regenerated neurons. The proneural transcription factor Ascl1 is upregulated in MG after retinal damage in zebrafish and is necessary for regeneration. Although Ascl1 is not expressed in mammalian MG after injury, forced expression of Ascl1 in mouse MG induces a neurogenic state in vitro and in vivo after NMDA (N-methyl-d-aspartate) damage in young mice...
July 26, 2017: Nature
https://www.readbyqxmd.com/read/28743168/calorie-restriction-reverses-age-related-alteration-of-cavernous-neurovascular-structure-in-the-rat
#5
A Limanjaya, K-M Song, M-J Choi, K Ghatak, N N Minh, D H Kang, J Ock, G N Yin, H Y Chung, J-K Ryu, J-K Suh
Calorie restriction (CR) refers to a reduction of calorie intake without compromising essential nutrients to avoid malnutrition. CR has been established as a non-genetic method of altering longevity and attenuating biological changes associated with aging. Aging is also an important risk factor for erectile dysfunction. The aim of this study was to examine whether CR diet can reverse the age-related alterations of erectile tissue in the aged rat. Four groups of rats were used: young rats (7 months) + ad libitum, aged rats (22 months) + ad libitum, young rats + CR diet, and aged rats + CR diet...
July 25, 2017: Andrology
https://www.readbyqxmd.com/read/28737745/electromagnetized-gold-nanoparticles-mediate-direct-lineage-reprogramming-into-induced-dopamine-neurons-in-vivo-for-parkinson-s-disease-therapy
#6
Junsang Yoo, Euiyeon Lee, Hee Young Kim, Dong-Ho Youn, Junghyun Jung, Hongwon Kim, Yujung Chang, Wonwoong Lee, Jaein Shin, Soonbong Baek, Wonhee Jang, Won Jun, Soochan Kim, Jongki Hong, Hi-Joon Park, Christopher J Lengner, Sang Hyun Moh, Youngeun Kwon, Jongpil Kim
Electromagnetic fields (EMF) are physical energy fields generated by electrically charged objects, and specific ranges of EMF can influence numerous biological processes, which include the control of cell fate and plasticity. In this study, we show that electromagnetized gold nanoparticles (AuNPs) in the presence of specific EMF conditions facilitate an efficient direct lineage reprogramming to induced dopamine neurons in vitro and in vivo. Remarkably, electromagnetic stimulation leads to a specific activation of the histone acetyltransferase Brd2, which results in histone H3K27 acetylation and a robust activation of neuron-specific genes...
July 17, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28720718/phosphorylation-of-amyloid-precursor-protein-by-mutant-lrrk2-promotes-aicd-activity-and-neurotoxicity-in-parkinson-s-disease
#7
Zhong-Can Chen, Wei Zhang, Ling-Ling Chua, Chou Chai, Rong Li, Lin Lin, Zhen Cao, Dario C Angeles, Lawrence W Stanton, Jian-He Peng, Zhi-Dong Zhou, Kah-Leong Lim, Li Zeng, Eng-King Tan
Mutations in LRRK2, which encodes leucine-rich repeat kinase 2, are the most common genetic cause of familial and sporadic Parkinson's disease (PD), a degenerative disease of the central nervous system that causes impaired motor function and, in advanced stages, dementia. Dementia is a common symptom of another neurodegenerative disease, Alzheimer's disease, and research suggests that there may be pathophysiological and genetic links between the two diseases. Aggregates of β amyloid [a protein produced through cleavage of amyloid precursor protein (APP)] are seen in both diseases and in PD patients carrying G2019S-mutant LRRK2...
July 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28697461/direct-induction-of-functional-neuronal-cells-from-fibroblast-like-cells-derived-from-adult-human-retina
#8
Lili Hao, Zhen Xu, Hui Sun, Wu Luo, Youchen Yan, Jing Wang, Jingyi Guo, Yizhi Liu, Shuyi Chen
Obtaining and manipulating neuronal cells are critical for neural biology basic mechanism studies and translational applications. Recent advances in protocol development and mechanism dissections have made direct induction of neuronal cells from other somatic cells (iN) a promising strategy for such purposes. In this study, we established a protocol to expand a population of fibroblast-like cells from adult human retinal tissues, which can be reprogrammed into iNs by forced expression of neurogenic transcription factors...
June 29, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28690140/new-neurons-in-adult-brain-distribution-molecular-mechanisms-and-therapies
#9
REVIEW
Annachiara Pino, Guido Fumagalli, Francesco Bifari, Ilaria Decimo
"Are new neurons added in the adult mammalian brain?" "Do neural stem cells activate following CNS diseases?" "How can we modulate their activation to promote recovery?" Recent findings in the field provide novel insights for addressing these questions from a new perspective. In this review, we will summarize the current knowledge about adult neurogenesis and neural stem cell niches in healthy and pathological conditions. We will first overview the milestones that have led to the discovery of the classical ventricular and hippocampal neural stem cell niches...
July 8, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28686866/direct-neuronal-reprogramming-achievements-hurdles-and-new-roads-to-success
#10
REVIEW
Sergio Gascón, Giacomo Masserdotti, Gianluca Luigi Russo, Magdalena Götz
The ability to directly reprogram mature cells to alternative fates challenges concepts of how cell identities are maintained, erased, and acquired. Recent advances in understanding and overcoming hurdles to direct neuronal conversion have provided new insights into mechanisms that maintain cell identity programs and have enabled high efficiency reprogramming in vivo. We discuss key cell-intrinsic molecular and metabolic constraints that influence the establishment of a new identity as well as environmental inputs from injured brains that favor or harm the conversion process...
July 6, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28685029/does-gastric-bypass-surgery-change-body-weight-set-point
#11
REVIEW
Z Hao, M B Mumphrey, C D Morrison, H Münzberg, J Ye, H R Berthoud
The relatively stable body weight during adulthood is attributed to a homeostatic regulatory mechanism residing in the brain which uses feedback from the body to control energy intake and expenditure. This mechanism guarantees that if perturbed up or down by design, body weight will return to pre-perturbation levels, defined as the defended level or set point. The fact that weight re-gain is common after dieting suggests that obese subjects defend a higher level of body weight. Thus, the set point for body weight is flexible and likely determined by the complex interaction of genetic, epigenetic and environmental factors...
December 2016: International Journal of Obesity Supplements
https://www.readbyqxmd.com/read/28664454/microrna-directed-neuronal-reprogramming-as-a-therapeutic-strategy-for-neurological-diseases
#12
REVIEW
Irene Faravelli, Stefania Corti
The loss of neurons due to injury and disease results in a wide spectrum of highly disabling neurological and neurodegenerative conditions, given the apparent limited capacity of endogenous repair of the adult central nervous system (CNS). Therefore, it is important to develop technologies that can promote de novo neural stem cell and neuron generation. Current insights in CNS development and cellular reprogramming have provided the knowledge to finely modulate lineage-restricted transcription factors and microRNAs (miRNA) to elicit correct neurogenesis...
June 29, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28654077/protocol-for-the-differentiation-of-human-induced-pluripotent-stem-cells-into-mixed-cultures-of-neurons-and-glia-for-neurotoxicity-testing
#13
Francesca Pistollato, David Canovas-Jorda, Dimitra Zagoura, Anna Price
Human pluripotent stem cells can differentiate into various cell types that can be applied to human-based in vitro toxicity assays. One major advantage is that the reprogramming of somatic cells to produce human induced pluripotent stem cells (hiPSCs) avoids the ethical and legislative issues related to the use of human embryonic stem cells (hESCs). HiPSCs can be expanded and efficiently differentiated into different types of neuronal and glial cells, serving as test systems for toxicity testing and, in particular, for the assessment of different pathways involved in neurotoxicity...
June 9, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28648365/direct-reprogramming-of-fibroblasts-via-a-chemically-induced-xen-like-state
#14
Xiang Li, Defang Liu, Yantao Ma, Xiaomin Du, Junzhan Jing, Lipeng Wang, Bingqing Xie, Da Sun, Shaoqiang Sun, Xueqin Jin, Xu Zhang, Ting Zhao, Jingyang Guan, Zexuan Yi, Weifeng Lai, Ping Zheng, Zhuo Huang, Yanzhong Chang, Zhen Chai, Jun Xu, Hongkui Deng
Direct lineage reprogramming, including with small molecules, has emerged as a promising approach for generating desired cell types. We recently found that during chemical induction of induced pluripotent stem cells (iPSCs) from mouse fibroblasts, cells pass through an extra-embryonic endoderm (XEN)-like state. Here, we show that these chemically induced XEN-like cells can also be induced to directly reprogram into functional neurons, bypassing the pluripotent state. The induced neurons possess neuron-specific expression profiles, form functional synapses in culture, and further mature after transplantation into the adult mouse brain...
August 3, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28646119/rest-suppression-mediates-neural-conversion-of-adult-human-fibroblasts-via-microrna-dependent-and-independent-pathways
#15
Janelle Drouin-Ouellet, Shong Lau, Per Ludvik Brattås, Daniella Rylander Ottosson, Karolina Pircs, Daniela A Grassi, Lucy M Collins, Romina Vuono, Annika Andersson Sjöland, Gunilla Westergren-Thorsson, Caroline Graff, Lennart Minthon, Håkan Toresson, Roger A Barker, Johan Jakobsson, Malin Parmar
Direct conversion of human fibroblasts into mature and functional neurons, termed induced neurons (iNs), was achieved for the first time 6 years ago. This technology offers a promising shortcut for obtaining patient- and disease-specific neurons for disease modeling, drug screening, and other biomedical applications. However, fibroblasts from adult donors do not reprogram as easily as fetal donors, and no current reprogramming approach is sufficiently efficient to allow the use of this technology using patient-derived material for large-scale applications...
August 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28641110/sox11-expression-promotes-regeneration-of-some-retinal-ganglion-cell-types-but-kills-others
#16
Michael W Norsworthy, Fengfeng Bei, Riki Kawaguchi, Qing Wang, Nicholas M Tran, Yi Li, Benedikt Brommer, Yiming Zhang, Chen Wang, Joshua R Sanes, Giovanni Coppola, Zhigang He
At least 30 types of retinal ganglion cells (RGCs) send distinct messages through the optic nerve to the brain. Available strategies of promoting axon regeneration act on only some of these types. Here we tested the hypothesis that overexpressing developmentally important transcription factors in adult RGCs could reprogram them to a "youthful" growth-competent state and promote regeneration of other types. From a screen of transcription factors, we identified Sox11 as one that could induce substantial axon regeneration...
June 21, 2017: Neuron
https://www.readbyqxmd.com/read/28637872/hydrogen-sulfide-modulates-eukaryotic-translation-initiation-factor-2%C3%AE-eif2%C3%AE-phosphorylation-status-in-the-integrated-stress-response-pathway
#17
Vinita Yadav, Xing-Huang Gao, Belinda Willard, Maria Hatzoglou, Ruma Banerjee, Omer Kabil
Hydrogen sulfide (H2S) regulates various physiological processes, including neuronal activity, vascular tone, inflammation, and energy metabolism. Moreover, H2S elicits cytoprotective effects against stressors in various cellular models of injury. However, the mechanism of the signaling pathways mediating the cytoprotective functions of H2S is not well understood. We previously uncovered a heme-dependent metabolic switch for transient induction of H2S production in the trans-sulfuration pathway. Here, we demonstrate that increased endogenous H2S production or its exogenous administration modulates major components of the integrated stress response promoting a metabolic state primed for stress response...
August 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28634230/similarity-in-gene-regulatory-networks-suggests-that-cancer-cells-share-characteristics-of-embryonic-neural-cells
#18
Zan Zhang, Anhua Lei, Liyang Xu, Lu Chen, Yonglong Chen, Xuena Zhang, Yan Gao, Xiaoli Yang, Min Zhang, Ying Cao
Cancer cells are immature cells resulting from cellular reprogramming by gene misregulation, and redifferentiation is expected to reduce malignancy. It is unclear, however, whether cancer cells can undergo terminal differentiation. Here, we show that inhibition of the epigenetic modification enzyme enhancer of zeste homolog 2 (EZH2), histone deacetylases 1 and 3 (HDAC1 and -3), lysine demethylase 1A (LSD1), or DNA methyltransferase 1 (DNMT1), which all promote cancer development and progression, leads to postmitotic neuron-like differentiation with loss of malignant features in distinct solid cancer cell lines...
August 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28627365/mitochondria-metabolic-reprogramming-in-the-formation-of-neurons-from-peripheral-cells-cause-or-consequence-and-the-implications-to-their-utility
#19
REVIEW
Gary E Gibson, Ankita Thakkar
The induction of pluripotent stem cells (iPSC) from differentiated cells such as fibroblasts and their subsequent conversion to neural progenitor cells (NPC) and finally to neurons is intriguing scientifically, and its potential to medicine nearly infinite, but unrealized. A better understanding of the changes at each step of the transformation will enable investigators to use them better to model neurological disease. Each step of conversion from a differentiated cell to an iPSC to a NPC to neurons requires large changes in glycolysis including aerobic glycolysis, the pentose shunt, the tricarboxylic acid cycle, the electron transport chain and in the production of reactive oxygen species (ROS)...
June 13, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28614042/bnip3l-nix-dependent-mitophagy-regulates-cell-differentiation-via-metabolic-reprogramming
#20
Lorena Esteban-Martínez, Patricia Boya
Macroautophagy/autophagy is the process by which cellular components are degraded and recycled within the lysosome. These components include mitochondria, the selective degradation of which is known as mitophagy. Mitochondria are dynamic organelles that constantly adapt their morphology, function, and number to accommodate the metabolic needs of the cell. Extensive metabolic reconfiguration occurs during cell differentiation, when mitochondrial activity increases in most cell types. However, our data demonstrate that during physiological retinal ganglion cell (RGC) development, mitophagy-dependent metabolic reprogramming towards glycolysis regulates numbers of RGCs, which are the first neurons to differentiate in the retina and whose axons form the optic nerve...
June 14, 2017: Autophagy
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