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https://www.readbyqxmd.com/read/28445465/assembly-of-functionally-integrated-human-forebrain-spheroids
#1
Fikri Birey, Jimena Andersen, Christopher D Makinson, Saiful Islam, Wu Wei, Nina Huber, H Christina Fan, Kimberly R Cordes Metzler, Georgia Panagiotakos, Nicholas Thom, Nancy A O'Rourke, Lars M Steinmetz, Jonathan A Bernstein, Joachim Hallmayer, John R Huguenard, Sergiu P Paşca
The development of the nervous system involves a coordinated succession of events including the migration of GABAergic (γ-aminobutyric-acid-releasing) neurons from ventral to dorsal forebrain and their integration into cortical circuits. However, these interregional interactions have not yet been modelled with human cells. Here we generate three-dimensional spheroids from human pluripotent stem cells that resemble either the dorsal or ventral forebrain and contain cortical glutamatergic or GABAergic neurons...
April 26, 2017: Nature
https://www.readbyqxmd.com/read/28440899/lissencephaly-expanded-imaging-and-clinical-classification
#2
Nataliya Di Donato, Sara Chiari, Ghayda M Mirzaa, Kimberly Aldinger, Elena Parrini, Carissa Olds, A James Barkovich, Renzo Guerrini, William B Dobyns
Lissencephaly ("smooth brain," LIS) is a malformation of cortical development associated with deficient neuronal migration and abnormal formation of cerebral convolutions or gyri. The LIS spectrum includes agyria, pachygyria, and subcortical band heterotopia. Our first classification of LIS and subcortical band heterotopia (SBH) was developed to distinguish between the first two genetic causes of LIS-LIS1 (PAFAH1B1) and DCX. However, progress in molecular genetics has led to identification of 19 LIS-associated genes, leaving the existing classification system insufficient to distinguish the increasingly diverse patterns of LIS...
April 25, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28440030/-identification-of-target-genes-downstream-of-semaphorin6a-plexina2-signaling-in-zebrafish
#3
Sarah E Emerson, Riley M St Clair, Ashley L Waldron, Sierra R Bruno, Anna Duong, Heather E Driscoll, Bryan A Ballif, Sarah McFarlane, Alicia M Ebert
BACKGROUND: Semaphorin (Sema)/Plexin (Plxn) signaling is important for many aspects of neuronal development, however the transcriptional regulation imposed by this signaling pathway is unknown. Previously, we identified an essential role for Sema6A/PlxnA2 signaling in regulating proliferation and cohesion of retinal precursor cells (RPCs) during early eye development. This study used RNA isolated from control, Sema6A-deficient, and PlxnA2-deficient zebrafish embryos in a microarray analysis to identify genes that were differentially expressed when this signaling pathway was disrupted...
April 25, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28439102/mecp2-regulated-mirnas-control-early-human-neurogenesis-through-differential-effects-on-erk-and-akt-signaling
#4
N Mellios, D A Feldman, S D Sheridan, J P K Ip, S Kwok, S K Amoah, B Rosen, B A Rodriguez, B Crawford, R Swaminathan, S Chou, Y Li, M Ziats, C Ernst, R Jaenisch, S J Haggarty, M Sur
Rett syndrome (RTT) is an X-linked, neurodevelopmental disorder caused primarily by mutations in the methyl-CpG-binding protein 2 (MECP2) gene, which encodes a multifunctional epigenetic regulator with known links to a wide spectrum of neuropsychiatric disorders. Although postnatal functions of MeCP2 have been thoroughly investigated, its role in prenatal brain development remains poorly understood. Given the well-established importance of microRNAs (miRNAs) in neurogenesis, we employed isogenic human RTT patient-derived induced pluripotent stem cell (iPSC) and MeCP2 short hairpin RNA knockdown approaches to identify novel MeCP2-regulated miRNAs enriched during early human neuronal development...
April 25, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28438491/immunomodulatory-functions-of-neuronal-guidance-proteins
#5
REVIEW
Valbona Mirakaj, Peter Rosenberger
Neuronal guidance proteins (NGPs) were originally identified for their role during the embryonic development of the nervous system. Recent years have seen the discovery of NGP functions during immune responses. In this context, NGPs were demonstrated to control leukocyte migration and the release of cytokines during conditions of acute inflammation, such as lung injury or sepsis. However, NGPs also display potent actions in the resolution of inflammation, chronic inflammatory conditions, the development of atherosclerosis, and during ischemia followed by reperfusion...
April 21, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28436683/dexmedetomidine-protects-pc12-cells-from-lidocaine-induced-cytotoxicity-through-downregulation-of-col3a1-mediated-by-mir-let-7b
#6
Qiong Wang, Yingjun She, Xiaobao Bi, Baisong Zhao, Xiangcai Ruan, Yonghong Tan
Safety concerns of some local anesthetics, such as lidocaine, have been raised in recent years due to potential neurological impairment. Dexmedetomidine may protect humans from neurotoxicity, and miR-let-7b is activated by nerve injury; however, the roles of miR-let-7b and its target gene in lidocaine-induced cytotoxicity are not well known. Through bioinformatics and a luciferase reporter assay, COL3A1 was suggested as a direct target gene of miR-let-7b. Here, we confirmed by measuring mRNA and protein levels that miR-let-7b was downregulated and COL3A1 was upregulated in lidocaine-treated cells, an observation that was reversed by dexmedetomidine...
April 24, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28436420/key-role-of-15-lo-15-hete-in-angiogenesis-and-functional-recovery-in-later-stages-of-post-stroke-mice
#7
Di Wang, Yu Liu, Li Chen, Pengyan Li, Youyang Qu, Yanmei Zhu, Yulan Zhu
This study sought to clarify the effects of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid in angiogenesis and neurological functional recovery after cerebral ischaemic stroke in mice. In vivo, we performed behavioural tests to determine functional recovery after stroke. Double immunofluorescence staining of CD31 and Ki67/PCNA was performed to evaluate the effects of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid on angiogenesis in an MCAO mouse model. In vitro, we investigated the effects of 15-hydroxyeicosatetraenoic acid on BMVEC proliferation and migration...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436114/all-trans-retinoic-acid-stimulates-overexpression-of-tumor-protein-d52-tpd52-isoform-3-and-neuronal-differentiation-of-imr-32-cells
#8
Sudha Sravanti Kotapalli, Chandrashekhar Dasari, Divya Duscharla, Karthik Reddy Kami Reddy, Manjula Kasula, Ramesh Ummanni
Tumor protein D52 (TPD52), a proto-oncogene is overexpressed in a variety of epithelial carcinomas and plays an important role in cell proliferation, migration and cell death. In the present study we found that the treatment of IMR-32 neuroblastoma (NB) cells with retinoic acid (RA) stimulates an increase in expression of TPD52. TPD52 expression is detectable after 72 h, can be maintained till differentiation of NB cells suggesting that TPD52 is involved in differentiation. Here, we demonstrate that TPD52 is essential for RA to promote differentiation of NB cells...
April 24, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28433420/dna-methylation-program-in-normal-and-alcohol-induced-thinning-cortex
#9
Nail Can Öztürk, Marisol Resendiz, Hakan Öztürk, Feng C Zhou
While cerebral underdevelopment is a hallmark of fetal alcohol spectrum disorders (FASD), the mechanism(s) guiding the broad cortical neurodevelopmental deficits are not clear. DNA methylation is known to regulate early development and tissue specification through gene regulation. Here, we examined DNA methylation in the onset of alcohol-induced cortical thinning in a mouse model of FASD. C57BL/6 (B6) mice were administered a 4% alcohol (v/v) liquid diet from embryonic (E) days 7-16, and their embryos were harvested at E17, along with isocaloric liquid diet and lab chow controls...
February 20, 2017: Alcohol
https://www.readbyqxmd.com/read/28431048/letter-extensive-migration-of-young-neurons-into-the-infant-human-frontal-lobe
#10
Adriano Barreto Nogueira, Ariel Barreto Nogueira, José Carlos Esteves Veiga, Manoel Jacobsen Teixeira
No abstract text is available yet for this article.
April 20, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28430000/neuroprotective-and-regenerative-roles-of-intranasal-wnt-3a-administration-after-focal-ischemic-stroke-in-mice
#11
Zheng Zachory Wei, James Ya Zhang, Tammi M Taylor, Xiaohuan Gu, Yingying Zhao, Ling Wei
Wnt signaling is a conserved pathway involved in expansion of neural progenitors and lineage specification during development. However, the role of Wnt signaling in the post-stroke brain has not been well-elucidated. We hypothesized that Wnt-3a would play an important role for neurogenesis and brain repair. Adult male mice were subjected to a focal ischemic stroke targeting the sensorimotor cortex. Mice that received Wnt-3a (2 µg/kg/day, 1 h after stroke and once a day for the next 2 days, intranasal delivery) had reduced infarct volume compared to stroke controls...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28422131/variants-in-cplx1-in-two-families-with-autosomal-recessive-severe-infantile-myoclonic-epilepsy-and-id
#12
Silke Redler, Tim M Strom, Thomas Wieland, Kirsten Cremer, Hartmut Engels, Felix Distelmaier, Jörg Schaper, Alma Küchler, Johannes R Lemke, Stephanie Jeschke, Nicole Schreyer, Heinrich Sticht, Margarete Koch, Hermann-Josef Lüdecke, Dagmar Wieczorek
For a large number of individuals with intellectual disability (ID), the molecular basis of the disorder is still unknown. However, whole-exome sequencing (WES) is providing more and more insights into the genetic landscape of ID. In the present study, we performed trio-based WES in 311 patients with unsolved ID and additional clinical features, and identified homozygous CPLX1 variants in three patients with ID from two unrelated families. All displayed marked developmental delay and migrating myoclonic epilepsy, and one showed a cerebellar cleft in addition...
April 19, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28418837/rapamycin-promotes-differentiation-increasing-%C3%AE-iii-tubulin-neun-and-neurod-while-suppressing-nestin-expression-in-glioblastoma-cells
#13
Michela Ferrucci, Francesca Biagioni, Paola Lenzi, Stefano Gambardella, Rosangela Ferese, Maria Teresa Calierno, Alessandra Falleni, Alfonso Grimaldi, Alessandro Frati, Vincenzo Esposito, Cristina Limatola, Francesco Fornai
Glioblastoma cells feature mammalian target of rapamycin (mTOR) up-regulation which relates to a variety of effects such as: lower survival, higher infiltration, high stemness and radio- and chemo-resistance. Recently, it was demonstrated that mTOR may produce a gene shift leading to altered protein expression. Therefore, in the present study we administered different doses of the mTOR inhibitor rapamycin to explore whether the transcription of specific genes are modified. By using a variety of methods we demonstrate that rapamycin stimulates gene transcription related to neuronal differentiation while inhibiting stemness related genes such as nestin...
March 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416692/immunomodulation-accelerated-neuronal-regeneration-following-selective-rod-photoreceptor-cell-ablation-in-the-zebrafish-retina
#14
David T White, Sumitra Sengupta, Meera T Saxena, Qingguo Xu, Justin Hanes, Ding Ding, Hongkai Ji, Jeff S Mumm
Müller glia (MG) function as inducible retinal stem cells in zebrafish, completely repairing the eye after damage. The innate immune system has recently been shown to promote tissue regeneration in which classic wound-healing responses predominate. However, regulatory roles for leukocytes during cellular regeneration-i.e., selective cell-loss paradigms akin to degenerative disease-are less well defined. To investigate possible roles innate immune cells play during retinal cell regeneration, we used intravital microscopy to visualize neutrophil, macrophage, and retinal microglia responses to induced rod photoreceptor apoptosis...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28415684/the-long-noncoding-rna-linc-ned125-controls-the-expression-of-medulloblastoma-driver-genes-by-microrna-sponge-activity
#15
Pietro Laneve, Agnese Po, Annarita Favia, Ivano Legnini, Vincenzo Alfano, Jessica Rea, Valerio Di Carlo, Valeria Bevilacqua, Evelina Miele, Angela Mastronuzzi, Andrea Carai, Franco Locatelli, Irene Bozzoni, Elisabetta Ferretti, Elisa Caffarelli
Long noncoding RNAs (lncRNAs) are major regulators of physiological and disease-related gene expression, particularly in the central nervous system. Dysregulated lncRNA expression has been documented in several human cancers, and their tissue-specificity makes them attractive candidates as diagnostic/prognostic biomarkers and/or therapeutic agents. Here we show that linc-NeD125, which we previously characterized as a neuronal-induced lncRNA, is significantly overexpressed in Group 4 medulloblastomas (G4 MBs), the largest and least well characterized molecular MB subgroup...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414797/big1-is-required-for-the-survival-of-deep-layer-neurons-neuronal-polarity-and-the-formation-of-axonal-tracts-between-the-thalamus-and-neocortex-in-developing-brain
#16
Jia-Jie Teoh, Tomohiko Iwano, Masataka Kunii, Nur Atik, Erda Avriyanti, Shin-Ichiro Yoshimura, Kenta Moriwaki, Akihiro Harada
BIG1, an activator protein of the small GTPase, Arf, and encoded by the Arfgef1 gene, is one of candidate genes for epileptic encephalopathy. To know the involvement of BIG1 in epileptic encephalopathy, we analyzed BIG1-deficient mice and found that BIG1 regulates neurite outgrowth and brain development in vitro and in vivo. The loss of BIG1 decreased the size of the neocortex and hippocampus. In BIG1-deficient mice, the neuronal progenitor cells (NPCs) and the interneurons were unaffected. However, Tbr1+ and Ctip2+ deep layer (DL) neurons showed spatial-temporal dependent apoptosis...
2017: PloS One
https://www.readbyqxmd.com/read/28413838/advanced-structural-multimodal-imaging-of-a-patient-with-subcortical-band-heterotopia
#17
Lohith G Kini, Ilya M Nasrallah, Carlos Coto, Lindsay C Ferraro, Kathryn A Davis
Subcortical band heterotopia (SBH) is a disorder of neuronal migration most commonly due to mutations of the Doublecortin (DCX) gene. A range of phenotypes is seen, with most patients having some degree of epilepsy and intellectual disability. Advanced diffusion and structural magnetic resonance imaging (MRI) sequences may be useful in identifying heterotopias and dysplasias of different sizes in drug-resistant epilepsy. We describe a patient with SBH and drug-resistant epilepsy and investigate neurite density, neurite dispersion, and diffusion parameters as compared to a healthy control through the use of multiple advanced MRI modalities...
December 2016: Epilepsia Open
https://www.readbyqxmd.com/read/28413826/medial-ganglionic-eminence-progenitors-transplanted-into-hippocampus-integrate-in-a-functional-and-subtype-appropriate-manner
#18
Jui-Yi Hsieh, Scott C Baraban
Medial ganglionic eminence (MGE) transplantation rescues disease phenotypes in various preclinical models with interneuron deficiency or dysfunction, including epilepsy. While underlying mechanism(s) remains unclear to date, a simple explanation is that appropriate synaptic integration of MGE-derived interneurons elevates GABA-mediated inhibition and modifies the firing activity of excitatory neurons in the host brain. However, given the complexity of interneurons and potential for transplant-derived interneurons to integrate or alter the host network in unexpected ways, it remains unexplored whether synaptic connections formed by transplant-derived interneurons safely mirror those associated with endogenous interneurons...
March 2017: ENeuro
https://www.readbyqxmd.com/read/28412554/prompt-peripheral-nerve-regeneration-induced-by-a-hierarchically-aligned-fibrin-nanofiber-hydrogel
#19
Jinrong Du, Jianheng Liu, Shenglian Yao, Haiquan Mao, Jiang Peng, Xun Sun, Zheng Cao, Yongdong Yang, Bo Xiao, Yiguo Wang, Peifu Tang, Xiumei Wang
Fibrin plays a crucial role in peripheral nerve regeneration, which could occur spontaneously in the format of longitudinally oriented fibrin cables during the initial stage of nerve regeneration. This fibrin cable can direct migration and proliferation of Schwann cells and axonal regrowth, which is very important to nerve regeneration. In the present study, we prepared a three-dimensional hierarchically aligned fibrin nanofiber hydrogel (AFG) through electrospinning and molecular self-assembly to resemble the architecture and biological function of the native fibrin cable...
April 12, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28412371/the-anti-inflammatory-effect-of-tramadol-in-the-temporomandibular-joint-of-rats
#20
Simone Monaliza S Lamana, Marcelo H Napimoga, Ana Paula Camatta Nascimento, Fabiana F Freitas, Daniele R de Araujo, Mariana S Quinteiro, Cristina G Macedo, Carlos L Fogaça, Juliana T Clemente-Napimoga
Tramadol is a centrally acting analgesic drug able to prevent nociceptor sensitization when administered into the temporomandibular joint (TMJ) of rats. The mechanism underlying the peripheral anti-inflammatory effect of tramadol remains unknown. This study demonstrated that intra-TMJ injection of tramadol (500µg/TMJ) was able to inhibit the nociceptive response induced by 1.5% formalin or 1.5% capsaicin, suggesting that tramadol has an antinociceptive effect, acting directly on the primary nociceptive neurons activating the nitric oxide/cyclic guanosine monophosphate signaling pathway...
April 12, 2017: European Journal of Pharmacology
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