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Haruo Okado
The mechanisms regulating the formation of the cerebral cortex have been well studied. In the developing cortex, Rp58 (also known Znf238, Znp238, and Zbtb18), which encodes a sequence-specific transcriptional repressor, is expressed in glutamatergic projection neurons and progenitor cells. Targeted deletion of Rp58 leads to dysplasia of the neocortex and hippocampus, a reduction in the number of mature cortical neurons, and defects in laminar organization due to abnormal neuronal migration within the cortical plate...
March 1, 2018: Brain Research
Xing-Guang Liang, Chao Tan, Cheng-Kun Wang, Rong-Rong Tao, Yu-Jie Huang, Kui-Fen Ma, Kohji Fukunaga, Ming-Zhu Huang, Feng Han
OBJECTIVE: The cholinergic deficit is thought to underlie progressed cognitive decline in Alzheimer Disease. The lineage reprogramming of somatic cells into cholinergic neurons may provide strategies toward cell-based therapy of neurodegenerative diseases. METHODS AND RESULTS: Here, we found that a combination of neuronal transcription factors, including Ascl1, Myt1l, Brn2, Tlx3, and miR124 (5Fs) were capable of directly converting human brain vascular pericytes (HBVPs) into cholinergic neuronal cells...
February 17, 2018: CNS Neuroscience & Therapeutics
Maria M Gridina, Natalia M Matveeva, Veniamin S Fishman, Aleksei G Menzorov, Helen A Kizilova, Nikolay A Beregovoy, Igor I Kovrigin, Inna E Pristyazhnyuk, Igor P Oscorbin, Maxim L Filipenko, Anna A Kashevarova, Nikolay A Skryabin, Tatyana V Nikitina, Elena A Sazhenova, Ludmila P Nazarenko, Igor N Lebedev, Oleg L Serov
Copy number variations (CNVs) of the human CNTN6 gene caused by megabase-scale microdeletions or microduplications in the 3p26.3 region are often the cause of neurodevelopmental disorders, including intellectual disability and developmental delay. Surprisingly, patients with different copy numbers of this gene display notable overlapping of neuropsychiatric symptoms. The complexity of the study of human neuropathologies is associated with the inaccessibility of brain material. This problem can be overcome through the use of reprogramming technologies that permit the generation of induced pluripotent stem (iPS) cells from fibroblasts and their subsequent in vitro differentiation into neurons...
January 11, 2018: Molecular Neurobiology
Qingqing Liu, Qi Qin, Hongxue Sun, Di Zhong, Ran An, Yushuang Tian, Hongping Chen, Jing Jin, Haining Wang, Guozhong Li
AIMS: The aim of the study is to evaluate the neuroprotective effects of olfactory ensheathing cells (OECs) with the overexpression of nuclear receptor-related factor 1 (Nurr1) and neurogenin 2 (Ngn2) in experimental models of Parkinson's disease (PD) and to elucidate the potential mechanism underlying the neuroprotective effects of OECs-Nurr1-Ngn2. MATERIALS AND METHODS: In vitro study, OECs-Nurr1-Ngn2 conditioned medium (CM) was added to MPP+-treated PC12 cells for 24h, and then the viability of PC12 cells, oxidative stress and apoptosis were detected...
December 29, 2017: Life Sciences
Simone Ferreira Lemes, Anelise Cristina Parras de Souza, Tanyara Baliani Payolla, Milena Diorio Versutti, Albina de Fátima da Silva Ramalho, Cristiano Mendes-da-Silva, Camilla Mendes Souza, Marciane Milanski, Adriana Souza Torsoni, Marcio Alberto Torsoni
Studies show that maternal consumption of a high-fat diet (HFD) can impair the formation of hypothalamic neuronal circuits in mouse offspring. This damage can be mediated by Notch1/Hes5 signaling activation, leading to repression of proneural factors such as Mash1 and Ngn2/3, which are essential for neuronal differentiation and neurogenesis. Thus, we aimed to investigate the effects of maternal HFD consumption during gestation and lactation on the Notch1/Mash1 pathway in the hypothalamus and arcuate nucleus (ARC) of mouse offspring (neonates and 28 days old)...
February 10, 2018: Neuroscience
Xian Zhang, Rui Su, Zhengyang Cheng, Wanbo Zhu, Yelin Li, Yongzhong Wang, Jian Du, Yihong Cai, Qingli Luo, Jilong Shen, Li Yu
BACKGROUND: Congenital infection of Toxoplasma gondii is an important factor causing birth defects. The neural stem cells (NSCs) are found to be one of the target cells for the parasite during development of the brain. As a key virulence factor of the parasite that hijacks host cellular functions, ROP18 has been demonstrated to mediate the inhibition of host innate and adaptive immune responses through specific binding different host immunity related molecules. However, its pathogenic actions in NSCs remain elusive...
November 23, 2017: Parasites & Vectors
Simone Mesman, Marten P Smidt
The basic helix-loop-helix (bHLH) protein family has previously been shown to be involved in the development of mesodiencephalic dopaminergic (mdDA) neurons in the murine midbrain. Specifically, Ngn2 and Mash1 are known to have a role in the specification of neural progenitors in the ventricular zone (VZ) of the midbrain towards an mdDA neuronal cell-fate. Furthermore, other members of the bHLH protein family, the E-box factors, are expressed in the developing midbrain and are thought to have a role in neuronal differentiation...
2017: Frontiers in Molecular Neuroscience
Ki Chan Kim, Chang Soon Choi, Edson Luck T Gonzales, Darine Froy N Mabunga, Sung Hoon Lee, Se Jin Jeon, Ram Hwangbo, Minha Hong, Jong Hoon Ryu, Seol-Heui Han, Geon Ho Bahn, Chan Young Shin
The valproic acid (VPA)-induced animal model is one of the most widely utilized environmental risk factor models of autism. Autism spectrum disorder (ASD) remains an insurmountable challenge among neurodevelopmental disorders due to its heterogeneity, unresolved pathological pathways and lack of treatment. We previously reported that VPA-exposed rats and cultured rat primary neurons have increased Pax6 expression during post-midterm embryonic development which led to the sequential upregulation of glutamatergic neuronal markers...
October 2017: Experimental Neurobiology
Haoyu Wang, Wenrui Ban, Tao Wang, Zhuo Li, Xiaoqian Dang
The aim of this study was to perform neural differentiation of mesenchymal stem cells derived from Wharton's jelly of human umbilical cord (HUMSCs) and explore the role of miR-20b and miR-106a, which may regulate Neurogenin-2 (Ngn2) expression during the neural differentiation. HUMSCs were cultured and induced in vitro. The cells were stained for nestin and microtubule-associated protein 2 (MAP2) by immunofluorescence. The interactional binding sites between the 3'-untranslated region (3'-UTR) of Ngn2 mRNA and miR-20b or miR-106a were predicted by bioinformatics and identified by a dual-luciferase assay...
December 13, 2017: Neuroreport
Manisha Singh, Anupama Kakkar, Rinkey Sharma, O P Kharbanda, Nitika Monga, Manish Kumar, Shantanu Chowdhary, Balram Airan, Sujata Mohanty
To understand the process of neurogenesis, generation of functional dopaminergic (DAergic) neurons from human mesenchymal stem cells (hMSCs) is important. BDNF has been reported to be responsible for inducing neuronal maturation and functionality. Previously, we have reported the efficient generation of neurons from human bone marrow derived MSCs using FGF2 alone. We hypothesize that hMSCs from various tissues [(bone marrow (BM), adipose tissue (AD) and dental pulp (DP)], if treated with BDNF on 9(th) day of induction, alongwith FGF2 will generate functional DAergic neurons...
September 4, 2017: Scientific Reports
Vladimir V Salmin, Yulia K Komleva, Natalia V Kuvacheva, Andrey V Morgun, Elena D Khilazheva, Olga L Lopatina, Elena A Pozhilenkova, Konstantin A Shapovalov, Yulia A Uspenskaya, Alla B Salmina
Impairment of hippocampal adult neurogenesis in aging or degenerating brain is a well-known phenomenon caused by the shortage of brain stem cell pool, alterations in the local microenvironment within the neurogenic niches, or deregulation of stem cell development. Environmental enrichment (EE) has been proposed as a potent tool to restore brain functions, to prevent aging-associated neurodegeneration, and to cure neuronal deficits seen in neurodevelopmental and neurodegenerative disorders. Here, we report our data on the effects of environmental enrichment on hippocampal neurogenesis in vivo and neurosphere-forming capacity of hippocampal stem/progenitor cells in vitro...
2017: Frontiers in Aging Neuroscience
Anupama Dey, Parisa Farzanehfar, Elena V Gazina, Tim D Aumann
The birth of new neurons, or neurogenesis, in the adult midbrain is important for progressing dopamine cell-replacement therapies for Parkinson's disease. Most studies suggest newborn cells remain undifferentiated or differentiate into glia within the adult midbrain. However, some studies suggest nestin+neural precursor cells (NPCs) have a propensity to generate new neurons here. We sought to confirm this by administering tamoxifen to adult NesCreER(T2)/R26eYFP transgenic mice, which permanently labelled adult nestin-expressing cells and their progeny with enhanced yellow fluorescent protein (eYFP)...
August 2017: Stem Cell Research
Long Yan, Yue Li, Zixiao Shi, Xiaoyin Lu, Jiao Ma, Baoyang Hu, Jianwei Jiao, Hongmei Wang
The zinc finger E-box-binding transcription factor Zeb1 plays a pivotal role in the epithelial-mesenchymal transition. Numerous studies have focused on the molecular mechanisms by which Zeb1 contributes to this process. However, the functions of Zeb1 beyond the epithelial-mesenchymal transition remain largely elusive. Using a transdifferentiation system to convert mouse embryonic fibroblasts (MEFs) into functional neurons via the neuronal transcription factors achaete-scute family bHLH (basic helix-loop-helix) transcription factor1 (Ascl1), POU class 3 homeobox 2 (POU3F2/Brn2), and neurogenin 2 (Neurog2, Ngn2) (ABN), we found that Zeb1 was up-regulated during the early stages of transdifferentiation...
August 4, 2017: Journal of Biological Chemistry
Parisa Farzanehfar, Malcolm K Horne, Tim D Aumann
Generation of new dopamine (DA) neurons in the adult midbrain is a controversial issue in development of better treatments for Parkinson's disease (PD). Previous research suggests Nestin-expressing neural precursor cells (NPCs) have a propensity to differentiate into neurons here, including DA neurons. In the present study we sought confirmation of this by studying gene expression in single Nestin-expressing cells and their progeny/ontogeny within the adult mouse midbrain. Cells were identified by administering a pulse of Tamoxifen to adult Nestin-CreER(T2)×R26eYFP transgenic mice...
May 1, 2017: Neuroscience Letters
Mitsunori D Arai, Bo Zhan, Atsuko Maruyama, Akiko Matsui-Harada, Kazuhiro Horinouchi, Shoji Komai
Neural stem cell (NSC) transplantation is a promising therapeutic modality for various nervous-system disorders; however, poor survival and differentiation of the transplanted NSCs limit their therapeutic efficacy. This study elucidated the effect of additive rehabilitative therapy with enriched environment (EE) and of achaete-scute homolog 1 (Mash1) and neurogenin2 (Ngn2) transduction on the fate of NSCs (P28-P35) transplanted into the primary somatosensory cortex (PSC) of mice. NSCs transplanted into the PSC differentiated into neurons and astrocytes and exhibited typical excitatory and synaptic response in mice housed in standard cages or in the EE...
February 15, 2017: Journal of the Neurological Sciences
Kohei Homma, Sumiko Usui, Makoto Kaneda
Fluorescent reporter gene knock-in induced pluripotent stem cell (iPSC) lines have been used to evaluate the efficiency of differentiation into specific cell lineages. Here, we report a knock-in strategy for the generation of human iPSC reporter lines in which a 2A peptide sequence and a red fluorescent protein (E2-Crimson) gene were inserted at the termination codon of the cone-rod homeobox (Crx) gene, a photoreceptor-specific transcriptional factor gene. The knock-in iPSC lines were differentiated into fluorescence-expressing cells in 3D retinal differentiation culture, and the fluorescent cells also expressed Crx specifically in the nucleus...
March 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Silvia Velasco, Mahmoud M Ibrahim, Akshay Kakumanu, Görkem Garipler, Begüm Aydin, Mohamed Ahmed Al-Sayegh, Antje Hirsekorn, Farah Abdul-Rahman, Rahul Satija, Uwe Ohler, Shaun Mahony, Esteban O Mazzoni
Direct cell programming via overexpression of transcription factors (TFs) aims to control cell fate with the degree of precision needed for clinical applications. However, the regulatory steps involved in successful terminal cell fate programming remain obscure. We have investigated the underlying mechanisms by looking at gene expression, chromatin states, and TF binding during the uniquely efficient Ngn2, Isl1, and Lhx3 motor neuron programming pathway. Our analysis reveals a highly dynamic process in which Ngn2 and the Isl1/Lhx3 pair initially engage distinct regulatory regions...
February 2, 2017: Cell Stem Cell
J Xu, B J Hartley, P Kurup, A Phillips, A Topol, M Xu, C Ononenyi, E Foscue, S-M Ho, T D Baguley, N Carty, C S Barros, U Müller, S Gupta, P Gochman, J Rapoport, J A Ellman, C Pittenger, B Aronow, A C Nairn, M W Nestor, P J Lombroso, K J Brennand
The brain-specific tyrosine phosphatase, STEP (STriatal-Enriched protein tyrosine Phosphatase) is an important regulator of synaptic function. STEP normally opposes synaptic strengthening by increasing N-methyl D-aspartate glutamate receptor (NMDAR) internalization through dephosphorylation of GluN2B and inactivation of the kinases extracellular signal-regulated kinase 1/2 and Fyn. Here we show that STEP61 is elevated in the cortex in the Nrg1(+/-) knockout mouse model of schizophrenia (SZ). Genetic reduction or pharmacological inhibition of STEP prevents the loss of NMDARs from synaptic membranes and reverses behavioral deficits in Nrg1(+/-) mice...
October 18, 2016: Molecular Psychiatry
Kwaku Dad Abu-Bonsrah, Dongcheng Zhang, Donald F Newgreen
Chickens are an invaluable model for studying human diseases, physiology and especially development, but have lagged in genetic applications. With the advent of Programmable Engineered Nucleases, genetic manipulation has become efficient, specific and rapid. Here, we show that the CRISPR/Cas9 system can precisely edit the chicken genome. We generated HIRA, TYRP1, DICER, MBD3, EZH2, and 6 other gene knockouts in two chicken cell lines using the CRISPR/Cas9 system, with no off-target effects detected. We also showed that very large deletions (>75 kb) could be achieved...
October 3, 2016: Scientific Reports
Gabriel Rusanescu, Jianren Mao
Unilateral peripheral nerve chronic constriction injury (CCI) has been widely used as a research model of human neuropathic pain. Recently, CCI has been shown to induce spinal cord adult neurogenesis, which may contribute to the chronic increase in nociceptive sensitivity. Here, we show that CCI also induces rapid and profound asymmetrical anatomical rearrangements in the adult rodent cerebellum and pons. This remodelling occurs throughout the hindbrain, and in addition to regions involved in pain processing, also affects other sensory modalities...
February 2017: Journal of Cellular and Molecular Medicine
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