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https://www.readbyqxmd.com/read/28198703/implantable-optoelectronic-probes-for-in-vivo-optogenetics
#1
Ege Iseri, Duygu Kuzum
More than a decade has passed since optics and genetics came together and lead to the emerging technologies of optogenetics. The advent of light-sensitive opsins made it possible to optically trigger the neurons into activation or inhibition by using visible light. The importance of spatiotemporally isolating a segment of a neural network and controlling nervous signaling in a precise manner has driven neuroscience researchers and engineers to invest great efforts in designing high precision in-vivo implantable devices...
February 15, 2017: Journal of Neural Engineering
https://www.readbyqxmd.com/read/28191903/efficient-genome-editing-in-the-mouse-brain-by-local-delivery-of-engineered-cas9-ribonucleoprotein-complexes
#2
Brett T Staahl, Madhurima Benekareddy, Claire Coulon-Bainier, Ashwin A Banfal, Stephen N Floor, Jennifer K Sabo, Cole Urnes, Gabriela Acevedo Munares, Anirvan Ghosh, Jennifer A Doudna
We demonstrate editing of post-mitotic neurons in the adult mouse brain following injection of Cas9 ribonucleoprotein (RNP) complexes in the hippocampus, striatum and cortex. Engineered variants of Cas9 with multiple SV40 nuclear localization sequences enabled a tenfold increase in the efficiency of neuronal editing in vivo. These advances indicate the potential of genome editing in the brain to correct or inactivate the underlying genetic causes of neurological diseases.
February 13, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28158225/visualizing-the-enteric-nervous-system-using-genetically-engineered-double-reporter-mice-comparison-with-immunofluorescence
#3
Yanfen Jiang, Hui Dong, Lars Eckmann, Elaine M Hanson, Katherine C Ihn, Ravinder K Mittal
BACKGROUND AND AIMS: The enteric nervous system (ENS) plays a crucial role in the control of gastrointestinal motility, secretion and absorption functions. Immunohistochemistry has been widely used to visualize neurons of the ENS for more than two decades. Genetically engineered mice that report specific proteins can also be used to visualize neurons of the ENS. The goal of our study was to develop a mouse that expresses fluorescent neuronal nitric oxide synthase (nNOS) and choline acetyltransferase (ChAT), the two proteins expressed in 95% of the ENS neurons...
2017: PloS One
https://www.readbyqxmd.com/read/28137877/camkii-modulates-sodium-current-in-neurons-from-epileptic-scn2a-mutant-mice
#4
Christopher H Thompson, Nicole A Hawkins, Jennifer A Kearney, Alfred L George
Monogenic epilepsies with wide-ranging clinical severity have been associated with mutations in voltage-gated sodium channel genes. In the Scn2a(Q54) mouse model of epilepsy, a focal epilepsy phenotype is caused by transgenic expression of an engineered NaV1.2 mutation displaying enhanced persistent sodium current. Seizure frequency and other phenotypic features in Scn2a(Q54) mice depend on genetic background. We investigated the neurophysiological and molecular correlates of strain-dependent epilepsy severity in this model...
January 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28133476/neuronal-activity-controls-the-development-of-interneurons-in-the-somatosensory-cortex
#5
Rachel Babij, Natalia De Marco Garcia
BACKGROUND: Neuronal activity in cortical areas regulates neurodevelopment by interacting with defined genetic programs to shape the mature central nervous system. Electrical activity is conveyed to sensory cortical areas via intracortical and thalamocortical neurons, and includes oscillatory patterns that have been measured across cortical regions. OBJECTIVE: In this work, we review the most recent findings about how electrical activity shapes the developmental assembly of functional circuitry in the somatosensory cortex, with an emphasis on interneuron maturation and integration...
December 2016: Frontiers in Biology
https://www.readbyqxmd.com/read/28132681/human-mesenchymal-stem-cells-genetically-engineered-to-overexpress-brain-derived-neurotrophic-factor-improve-outcomes-in-huntington-s-disease-mouse-models
#6
Kari Pollock, Heather Dahlenburg, Haley Nelson, Kyle D Fink, Whitney Cary, Kyle Hendrix, Geralyn Annett, Audrey Torrest, Peter Deng, Joshua Gutierrez, Catherine Nacey, Karen Pepper, Stefanos Kalomoiris, Johnathon D Anderson, Jeannine McGee, William Gruenloh, Brian Fury, Gerhard Bauer, Alexandria Duffy, Theresa Tempkin, Vicki Wheelock, Jan A Nolta
Huntington's disease (HD) is a fatal degenerative autosomal dominant neuropsychiatric disease that causes neuronal death and is characterized by progressive striatal and then widespread brain atrophy. Brain-derived neurotrophic factor (BDNF) is a lead candidate for the treatment of HD, as it has been shown to prevent cell death and to stimulate the growth and migration of new neurons in the brain in transgenic mouse models. BDNF levels are reduced in HD postmortem human brain. Previous studies have shown efficacy of mesenchymal stem/stromal cells (MSC)/BDNF using murine MSCs, and the present study used human MSCs to advance the therapeutic potential of the MSC/BDNF platform for clinical application...
May 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28104683/panin-neuroendocrine-cells-promote-tumorigenesis-via-neuronal-crosstalk
#7
Smrita Sinha, Ya-Yuan Fu, Adrien Grimont, Maren Ketcham, Kelly J Lafaro, Joseph A Saglimbeni, Gokce Askan, Jennifer M Bailey, Jerry P Melchor, Yi Zhong, Min Geol Joo, Olivera Grbovic-Huezo, In-Hong Yang, Olca Basturk, Lindsey Baker, Youngkyu Park, Robert C Kurtz, David A Tuveson, Steven D Leach, Pankaj Pasricha
Nerves are a notable feature of the tumor microenvironment in some epithelial tumors, but their role in the malignant progression of pancreatic ductal adenocarcinoma (PDAC) is uncertain. Here we identify dense innervation in the microenvironment of precancerous pancreatic lesions, known as pancreatic intraepithelial neoplasms (PanIN), and describe a unique subpopulation of neuroendocrine PanIN cells that express the neuropeptide substance P (SP) receptor Neurokinin 1-R (NK1-R). Using organoid culture, we demonstrated that sensory neurons promoted the proliferation of PanIN organoids via SP-NK1-R signaling and Stat3 activation...
January 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28097054/hydrogel-scaffolds-promote-neural-gene-expression-and-structural-reorganization-in-human-astrocyte-cultures
#8
V Bleu Knight, Elba E Serrano
Biomaterial scaffolds have the potential to enhance neuronal development and regeneration. Understanding the genetic responses of astrocytes and neurons to biomaterials could facilitate the development of synthetic environments that enable the specification of neural tissue organization with engineered scaffolds. In this study, we used high throughput transcriptomic and imaging methods to determine the impact of a hydrogel, PuraMatrix™, on human glial cells in vitro. Parallel studies were undertaken with cells grown in a monolayer environment on tissue culture polystyrene...
2017: PeerJ
https://www.readbyqxmd.com/read/28058503/genetic-manipulation-of-specific-neural-circuits-by-use-of-a-viral-vector-system
#9
REVIEW
Kenta Kobayashi, Shigeki Kato, Kazuto Kobayashi
To understand the mechanisms underlying higher brain functions, we need to analyze the roles of specific neuronal pathways or cell types forming the complex neural networks. In the neuroscience field, the transgenic approach has provided a useful gene engineering tool for experimental studies of neural functions. The conventional transgenic technique requires the appropriate promoter regions that drive a neuronal type-specific gene expression, but the promoter sequences specifically functioning in each neuronal type are limited...
January 5, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/27993709/divergence-and-inheritance-of-neocortical-heterotopia-in-inbred-and-genetically-engineered-mice
#10
Alyssa R Toia, Joshua A Cuoco, Anthony W Esposito, Jawad Ahsan, Alok Joshi, Bruce J Herron, German Torres, Valerie J Bolivar, Raddy L Ramos
Cortical function emerges from the intrinsic properties of neocortical neurons and their synaptic connections within and across lamina. Neurodevelopmental disorders affecting migration and lamination of the neocortex result in cognitive delay/disability and epilepsy. Molecular layer heterotopia (MLH), a dysplasia characterized by over-migration of neurons into layer I, are associated with cognitive deficits and neuronal hyperexcitability in humans and mice. The breadth of different inbred mouse strains that exhibit MLH and inheritance patterns of heterotopia remain unknown...
January 18, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/27984692/probing-deep-brain-circuitry-new-advances-in-in-vivo-calcium-measurement-strategies
#11
Kasey S Girven, Dennis R Sparta
The study of neuronal ensembles in awake and behaving animals is a critical question in contemporary neuroscience research. Through the examination of calcium fluctuations, which are correlated with neuronal activity, we are able to better understand complex neural circuits. Recently, the development of technologies including two-photon microscopy, miniature microscopes, and fiber photometry has allowed us to examine calcium activity in behaving subjects over time. Visualizing changes in intracellular calcium in vivo has been accomplished utilizing GCaMP, a genetically encoded calcium indicator...
February 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27976757/efficient-and-versatile-crispr-engineering-of-human-neurons-in-culture-to-model-neurological-disorders
#12
Ruth R Shah, Justyna Cholewa-Waclaw, Faith C J Davies, Katie M Paton, Ronan Chaligne, Edith Heard, Catherine M Abbott, Adrian P Bird
The recent identification of multiple new genetic causes of neurological disorders highlights the need for model systems that give experimental access to the underlying biology. In particular, the ability to couple disease-causing mutations with human neuronal differentiation systems would be beneficial. Gene targeting is a well-known approach for dissecting gene function, but low rates of homologous recombination in somatic cells (including neuronal cells) have traditionally impeded the development of robust cellular models of neurological disorders...
November 15, 2016: Wellcome Open Res
https://www.readbyqxmd.com/read/27974554/thymidine-kinase-negative-herpes-simplex-virus-1-can-efficiently-establish-persistent-infection-in-neural-tissues-of-nude-mice
#13
Chih-Yu Huang, Hui-Wen Yao, Li-Chiu Wang, Fang-Hsiu Shen, Sheng-Min Hsu, Shun-Hua Chen
: Herpes simplex virus 1 (HSV-1) establishes latency in neural tissues of immunocompetent mice but persists in both peripheral and neural tissues of lymphocyte-deficient mice. Thymidine kinase (TK) is believed to be essential for HSV-1 to persist in neural tissues of immunocompromised mice, because infectious virus of a mutant with defects in both TK and UL24 is detected only in peripheral tissues, but not in neural tissues, of severe combined immunodeficiency mice (T. Valyi-Nagy, R. M...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27974499/human-sod1-als-mutations-in-a-drosophila-knock-in-model-cause-severe-phenotypes-and-reveal-dosage-sensitive-gain-and-loss-of-function-components
#14
Aslı Şahin, Aaron Held, Kirsten Bredvik, Paxton Major, Toni-Marie Achilli, Abigail G Kerson, Kristi Wharton, Geoff Stilwell, Robert Reenan
Amyotrophic Lateral Sclerosis (ALS) is the most common adult-onset motor neuron disease and familial forms can be caused by numerous dominant mutations of the copper-zinc superoxide dismutase 1 (SOD1) gene. Substantial efforts have been invested in studying SOD1-ALS transgenic animal models; yet, the molecular mechanisms by which ALS-mutant SOD1 protein acquires toxicity are not well understood. ALS-like phenotypes in animal models are highly dependent on transgene dosage. Thus, issues of whether the ALS-like phenotypes of these models stem from overexpression of mutant alleles or from aspects of the SOD1 mutation itself are not easily deconvolved...
February 2017: Genetics
https://www.readbyqxmd.com/read/27874828/sf-1-expression-in-the-hypothalamus-is-required-for-beneficial-metabolic-effects-of-exercise
#15
Teppei Fujikawa, Carlos M Castorena, Mackenzie Pearson, Christine M Kusminski, Newaz Ahmed, Pavan K Battiprolu, Ki Woo Kim, Syann Lee, Joseph A Hill, Philipp E Scherer, William L Holland, Joel K Elmquist
Exercise has numerous beneficial metabolic effects. The central nervous system (CNS) is critical for regulating energy balance and coordinating whole body metabolism. However, a role for the CNS in the regulation of metabolism in the context of the exercise remains less clear. Here, using genetically engineered mice we assessed the requirement of steroidogenic factor-1 (SF-1) expression in neurons of the ventromedial hypothalamic nucleus (VMH) in mediating the beneficial effects of exercise on metabolism. We found that VMH-specific deletion of SF-1 blunts (a) the reductions in fat mass, (b) improvements in glycemia, and (c) increases in energy expenditure that are associated with exercise training...
November 22, 2016: ELife
https://www.readbyqxmd.com/read/27867348/better-targeting-better-efficiency-for-wide-scale-neuronal-transduction-with-the-synapsin-promoter-and-aav-php-b
#16
Kasey L Jackson, Robert D Dayton, Benjamin E Deverman, Ronald L Klein
Widespread genetic modification of cells in the central nervous system (CNS) with a viral vector has become possible and increasingly more efficient. We previously applied an AAV9 vector with the cytomegalovirus/chicken beta-actin (CBA) hybrid promoter and achieved wide-scale CNS transduction in neonatal and adult rats. However, this method transduces a variety of tissues in addition to the CNS. Thus we studied intravenous AAV9 gene transfer with a synapsin promoter to better target the neurons. We noted in systematic comparisons that the synapsin promoter drives lower level expression than does the CBA promoter...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27851729/in-vivo-genome-editing-via-crispr-cas9-mediated-homology-independent-targeted-integration
#17
Keiichiro Suzuki, Yuji Tsunekawa, Reyna Hernandez-Benitez, Jun Wu, Jie Zhu, Euiseok J Kim, Fumiyuki Hatanaka, Mako Yamamoto, Toshikazu Araoka, Zhe Li, Masakazu Kurita, Tomoaki Hishida, Mo Li, Emi Aizawa, Shicheng Guo, Song Chen, April Goebl, Rupa Devi Soligalla, Jing Qu, Tingshuai Jiang, Xin Fu, Maryam Jafari, Concepcion Rodriguez Esteban, W Travis Berggren, Jeronimo Lajara, Estrella Nuñez-Delicado, Pedro Guillen, Josep M Campistol, Fumio Matsuzaki, Guang-Hui Liu, Pierre Magistretti, Kun Zhang, Edward M Callaway, Kang Zhang, Juan Carlos Izpisua Belmonte
Targeted genome editing via engineered nucleases is an exciting area of biomedical research and holds potential for clinical applications. Despite rapid advances in the field, in vivo targeted transgene integration is still infeasible because current tools are inefficient, especially for non-dividing cells, which compose most adult tissues. This poses a barrier for uncovering fundamental biological principles and developing treatments for a broad range of genetic disorders. Based on clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) technology, here we devise a homology-independent targeted integration (HITI) strategy, which allows for robust DNA knock-in in both dividing and non-dividing cells in vitro and, more importantly, in vivo (for example, in neurons of postnatal mammals)...
December 1, 2016: Nature
https://www.readbyqxmd.com/read/27833556/increased-motor-impairing-effects-of-the-neuroactive-steroid-pregnanolone-in-mice-with-targeted-inactivation-of-the-gabaa-receptor-%C3%AE-2-subunit-in-the-cerebellum
#18
Elli Leppä, Anni-Maija Linden, Maria I Aller, Peer Wulff, Olga Vekovischeva, Bernhard Luscher, Hartmut Lüddens, William Wisden, Esa R Korpi
Endogenous neurosteroids and neuroactive steroids have potent and widespread actions on the brain via inhibitory GABAA receptors. In recombinant receptors and genetic mouse models their actions depend on the α, β, and δ subunits of the receptor, especially on those that form extrasynaptic GABAA receptors responsible for non-synaptic (tonic) inhibition, but they also act on synaptically enriched γ2 subunit-containing receptors and even on αβ binary receptors. Here we tested whether behavioral sensitivity to the neuroactive steroid agonist 5β-pregnan-3α-ol-20-one is altered in genetically engineered mouse models that have deficient GABAA receptor-mediated synaptic inhibition in selected neuronal populations...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27822501/inhibition-of-ikk%C3%AE-reduces-ethanol-consumption-in-c57bl-6j-mice
#19
Jay M Truitt, Yuri A Blednov, Jillian M Benavidez, Mendy Black, Olga Ponomareva, Jade Law, Morgan Merriman, Sami Horani, Kelly Jameson, Amy W Lasek, R Adron Harris, R Dayne Mayfield
Proinflammatory pathways in neuronal and non-neuronal cells are implicated in the acute and chronic effects of alcohol exposure in animal models and humans. The nuclear factor-κB (NF-κB) family of DNA transcription factors plays important roles in inflammatory diseases. The kinase IKKβ mediates the phosphorylation and subsequent proteasomal degradation of cytosolic protein inhibitors of NF-κB, leading to activation of NF-κB. The role of IKKβ as a potential regulator of excessive alcohol drinking had not previously been investigated...
September 2016: ENeuro
https://www.readbyqxmd.com/read/27816769/in-vivocharacterization-of-the-aspartyl-trna-synthetase-dars-homing-in-on-the-leukodystrophy-hbsl
#20
Dominik Fröhlich, Alexandra K Suchowerska, Ziggy H T Spencer, Georg von Jonquieres, Claudia B Klugmann, Andre Bongers, Fabien Delerue, Holly Stefen, Lars M Ittner, Thomas Fath, Gary D Housley, Matthias Klugmann
BACKGROUND: The recently diagnosed leukodystrophy Hypomyelination with Brain stem and Spinal cord involvement and Leg spasticity (HBSL) is caused by mutations of the cytoplasmic aspartyl-tRNA synthetase geneDARS. The physiological role of DARS in translation is to accurately pair aspartate with its cognate tRNA. Clinically, HBSL subjects show a distinct pattern of hypomyelination and develop progressive leg spasticity, variable cognitive impairment and epilepsy. To elucidate the underlying pathomechanism, we comprehensively assessed endogenous DARS expression in mice...
January 2017: Neurobiology of Disease
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