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https://www.readbyqxmd.com/read/29766029/seizure-suppressant-and-neuroprotective-effects-of-encapsulated-bdnf-producing-cells-in-a-rat-model-of-temporal-lobe-epilepsy
#1
Chiara Falcicchia, Giovanna Paolone, Dwaine F Emerich, Francesca Lovisari, William J Bell, Tracie Fradet, Lars U Wahlberg, Michele Simonato
Brain-derived neurotrophic factor (BDNF) may represent a therapeutic for chronic epilepsy, but evaluating its potential is complicated by difficulties in its delivery to the brain. Here, we describe the effects on epileptic seizures of encapsulated cell biodelivery (ECB) devices filled with genetically modified human cells engineered to release BDNF. These devices, implanted into the hippocampus of pilocarpine-treated rats, highly decreased the frequency of spontaneous seizures by more than 80%. These benefits were associated with improved cognitive performance, as epileptic rats treated with BDNF performed significantly better on a novel object recognition test...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29701954/neuronal-calcium-recording-with-an-engineered-tev-protease
#2
Brianna K O'Neill, Scott T Laughlin
Technologies for measuring the transient Ca2+ spikes that accompany neural signaling have revolutionized our understanding of the brain. Nevertheless, microscopic visualization of Ca2+ spikes on the timescale of neural activity across large brain regions or in thick specimens remains a significant challenge. The recent development of stable integrators of Ca2+ , instead of transient reporters, provides an avenue to investigate neural signaling in otherwise challenging systems. Here we describe an engineered Ca2+ -sensing enzyme consisting of a split Tobacco Etch Virus (TEV) protease with each half tethered to a calmodulin or M13 Ca2+ binding domain...
April 27, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29690872/identification-of-a-neuronal-population-in-the-telencephalon-essential-for-fear-conditioning-in-zebrafish
#3
Pradeep Lal, Hideyuki Tanabe, Maximiliano L Suster, Deepak Ailani, Yuri Kotani, Akira Muto, Mari Itoh, Miki Iwasaki, Hironori Wada, Emre Yaksi, Koichi Kawakami
BACKGROUND: Fear conditioning is a form of learning essential for animal survival and used as a behavioral paradigm to study the mechanisms of learning and memory. In mammals, the amygdala plays a crucial role in fear conditioning. In teleost, the medial zone of the dorsal telencephalon (Dm) has been postulated to be a homolog of the mammalian amygdala by anatomical and ablation studies, showing a role in conditioned avoidance response. However, the neuronal populations required for a conditioned avoidance response via the Dm have not been functionally or genetically defined...
April 25, 2018: BMC Biology
https://www.readbyqxmd.com/read/29675450/engineered-human-gastrointestinal-cultures-to-study-the-microbiome-and-infectious-diseases
#4
REVIEW
Sarah E Blutt, Sue E Crawford, Sasirekha Ramani, Winnie Y Zou, Mary K Estes
New models to study the intestine are key to understanding intestinal diseases and developing novel treatments. Intestinal organ-like culture systems (organoids and enteroids) have substantially advanced the study of the human gastrointestinal tract. Stem cell-derived cultures produce self-organizing structures that contain the multiple differentiated intestinal epithelial cell types including enterocytes, goblet, Paneth, and enteroendocrine cells. Understanding host-microbial interactions is one area in which these cultures are expediting major advancements...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29666700/oil-palm-phenolics-inhibit-the-in-vitro-aggregation-of-%C3%AE-amyloid-peptide-into-oligomeric-complexes
#5
Robert P Weinberg, Vera V Koledova, Hyeari Shin, Jennifer H Park, Yew Ai Tan, Anthony J Sinskey, Ravigadevi Sambanthamurthi, ChoKyun Rha
Alzheimer's disease is a severe neurodegenerative disease characterized by the aggregation of amyloid- β peptide (A β ) into toxic oligomers which activate microglia and astrocytes causing acute neuroinflammation. Multiple studies show that the soluble oligomers of A β 42 are neurotoxic and proinflammatory, whereas the monomers and insoluble fibrils are relatively nontoxic. We show that A β 42 aggregation is inhibited in vitro by oil palm phenolics (OPP), an aqueous extract from the oil palm tree (Elaeis guineensis) ...
2018: International Journal of Alzheimer's Disease
https://www.readbyqxmd.com/read/29614429/engineered-viral-vectors-for-functional-interrogation-deconvolution-and-manipulation-of-neural-circuits
#6
REVIEW
Sabrina Sun, David V Schaffer
Optimization of traditional replication-competent viral tracers has granted access to immediate synaptic partners of target neuronal populations, enabling the dissection of complex brain circuits into functional neural pathways. The excessive virulence of most conventional tracers, however, impedes their utility in revealing and genetically perturbing cellular function on long time scales. As a promising alternative, the natural capacity of adeno-associated viral (AAV) vectors to safely mediate persistent and robust gene expression has stimulated strong interest in adapting them for sparse neuronal labeling and physiological studies...
March 31, 2018: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29588398/the-light-chain-defines-the-duration-of-action-of-botulinum-toxin-serotype-a-subtypes
#7
Sabine Pellett, Marite Bradshaw, William H Tepp, Christina L Pier, Regina C M Whitemarsh, Chen Chen, Joseph T Barbieri, Eric A Johnson
Botulinum neurotoxin (BoNT) is the causative agent of botulism and a widely used pharmaceutical to treat a variety of neurological diseases. BoNTs are 150-kDa protein toxins organized into heavy chain (HC) and light chain (LC) domains linked by a disulfide bond. The HC selectively binds to neurons and aids cell entry of the enzymatically active LC. There are seven immunological BoNT serotypes (A to G); each serotype includes genetic variants, termed subtypes. Only two subtypes, BoNT/A1 and BoNT/B1, are currently used as therapeutics...
March 27, 2018: MBio
https://www.readbyqxmd.com/read/29561583/multifunctional-fibers-as-tools-for-neuroscience-and-neuroengineering
#8
Andres Canales, Seongjun Park, Antje Kilias, Polina Anikeeva
Multifunctional devices for modulation and probing of neuronal activity during free behavior facilitate studies of functions and pathologies of the nervous system. Probes composed of stiff materials, such as metals and semiconductors, exhibit elastic and chemical mismatch with the neural tissue, which is hypothesized to contribute to sustained tissue damage and gliosis. Dense glial scars have been found to encapsulate implanted devices, corrode their surfaces, and often yield poor recording quality in long-term experiments...
March 21, 2018: Accounts of Chemical Research
https://www.readbyqxmd.com/read/29535911/small-cell-lung-cancer-tumors-and-preclinical-models-display-heterogeneity-of-neuroendocrine-phenotypes
#9
Wei Zhang, Luc Girard, Yu-An Zhang, Tomohiro Haruki, Mahboubeh Papari-Zareei, Victor Stastny, Hans K Ghayee, Karel Pacak, Trudy G Oliver, John D Minna, Adi F Gazdar
Background: Small cell lung cancer (SCLC) is a deadly, high grade neuroendocrine (NE) tumor without recognized morphologic heterogeneity. However, over 30 years ago we described a SCLC subtype with "variant" morphology which did not express some NE markers and exhibited more aggressive growth. Methods: To quantitate NE properties of SCLCs, we developed a 50-gene expression-based NE score that could be applied to human SCLC tumors and cell lines, and genetically engineered mouse (GEM) models...
February 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29526002/migration-of-q-cells-in-caenorhabditis-elegans
#10
Yongping Chai, Zhiwen Zhu, Guangshuo Ou
During C. elegans larval development, the Q neuroblasts produce their lineage by three rounds of divisions along with continuous cell migrations. Their neuronal progeny is dispersed from the pharynx to the anus. This in vivo system to study cell migration is appealing for several reasons. The lineage development is stereotyped; functional analysis and genomic screens are rendered easy and powerful thanks to powerful tools; transgenic manipulations and genome engineering are efficient and can be conveniently combined with live-cell imaging...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29512130/conditional-manipulation-of-gene-function-in-human-cells-with-optimized-inducible-shrna
#11
Alessandro Bertero, Loukia Yiangou, Stephanie Brown, Daniel Ortmann, Matthias Pawlowski, Ludovic Vallier
The difficulties involved in conditionally perturbing complex gene expression networks represent major challenges toward defining the mechanisms controlling human development, physiology, and disease. We developed an OPTimized inducible KnockDown (OPTiKD) platform that addresses the limitations of previous approaches by allowing streamlined, tightly-controlled, and potent loss-of-function experiments for both single and multiple genes. The method relies on single-step genetic engineering of the AAVS1 genomic safe harbor with an optimized tetracycline-responsive cassette driving one or more inducible short hairpin RNAs (shRNAs)...
February 28, 2018: Current Protocols in Stem Cell Biology
https://www.readbyqxmd.com/read/29497380/triple-gene-therapy-for-stroke-a-proof-of-concept-in-vivo-study-in-rats
#12
Mikhail E Sokolov, Farid V Bashirov, Vage A Markosyan, Tatyana V Povysheva, Filip O Fadeev, Andrey A Izmailov, Maxim S Kuztetsov, Zufar Z Safiullov, Maxim M Shmarov, Boris S Naroditskyi, András Palotás, Rustem R Islamov
Natural brain repair after stroke is extremely limited, and current therapeutic options are even more scarce with no clinical break-through in sight. Despite restricted regeneration in the central nervous system, we have previously proved that human umbilical cord blood mono-nuclear cells (UCB-MC) transduced with adenoviral vectors carrying genes encoding vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF), and neural cell adhesion molecule (NCAM) successfully rescued neurons in amyotrophic lateral sclerosis and spinal cord injury...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29485996/characterization-of-knockin-mice-at-the-rosa26-tac1-and-plekhg1-loci-generated-by-homologous-recombination-in-oocytes
#13
Youmei Wu, María José Luna, Lauren S Bonilla, Nicholas J P Ryba, James M Pickel
Design and engineering of complex knockin mice has revolutionized the in vivo manipulation of genetically defined cells. Recently development of the bacterial clustered regularly interspersed short palindromic repeats (CRISPR) associated protein 9 (Cas9) system for single site cleavage of mammalian genomes has opened the way for rapid generation of knockin mice by targeting homology directed repair to selected cleavage sites. We used this approach to generate new lines of mice that will be useful for a variety of aspects of neuroscience research...
2018: PloS One
https://www.readbyqxmd.com/read/29485402/alterations-of-in-vivo-ca1-network-activity-in-dp-16-1yey-down-syndrome-model-mice
#14
Matthieu Raveau, Denis Polygalov, Roman Boehringer, Kenji Amano, Kazuhiro Yamakawa, Thomas J McHugh
Down syndrome, the leading genetic cause of intellectual disability, results from an extra-copy of chromosome 21. Mice engineered to model this aneuploidy exhibit Down syndrome-like memory deficits in spatial and contextual tasks. While abnormal neuronal function has been identified in these models, most studies have relied on in vitro measures. Here, using in vivo recording in the Dp(16)1Yey model, we find alterations in the organization of spiking of hippocampal CA1 pyramidal neurons, including deficits in the generation of complex spikes...
February 27, 2018: ELife
https://www.readbyqxmd.com/read/29483642/a-robotic-multidimensional-directed-evolution-approach-applied-to-fluorescent-voltage-reporters
#15
Kiryl D Piatkevich, Erica E Jung, Christoph Straub, Changyang Linghu, Demian Park, Ho-Jun Suk, Daniel R Hochbaum, Daniel Goodwin, Eftychios Pnevmatikakis, Nikita Pak, Takashi Kawashima, Chao-Tsung Yang, Jeffrey L Rhoades, Or Shemesh, Shoh Asano, Young-Gyu Yoon, Limor Freifeld, Jessica L Saulnier, Clemens Riegler, Florian Engert, Thom Hughes, Mikhail Drobizhev, Balint Szabo, Misha B Ahrens, Steven W Flavell, Bernardo L Sabatini, Edward S Boyden
We developed a new way to engineer complex proteins toward multidimensional specifications using a simple, yet scalable, directed evolution strategy. By robotically picking mammalian cells that were identified, under a microscope, as expressing proteins that simultaneously exhibit several specific properties, we can screen hundreds of thousands of proteins in a library in just a few hours, evaluating each along multiple performance axes. To demonstrate the power of this approach, we created a genetically encoded fluorescent voltage indicator, simultaneously optimizing its brightness and membrane localization using our microscopy-guided cell-picking strategy...
April 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/29472486/single-cell-bioluminescence-imaging-of-deep-tissue-in-freely-moving-animals
#16
Satoshi Iwano, Mayu Sugiyama, Hiroshi Hama, Akiya Watakabe, Naomi Hasegawa, Takahiro Kuchimaru, Kazumasa Z Tanaka, Megumu Takahashi, Yoko Ishida, Junichi Hata, Satoshi Shimozono, Kana Namiki, Takashi Fukano, Masahiro Kiyama, Hideyuki Okano, Shinae Kizaka-Kondoh, Thomas J McHugh, Tetsuo Yamamori, Hiroyuki Hioki, Shojiro Maki, Atsushi Miyawaki
Bioluminescence is a natural light source based on luciferase catalysis of its substrate luciferin. We performed directed evolution on firefly luciferase using a red-shifted and highly deliverable luciferin analog to establish AkaBLI, an all-engineered bioluminescence in vivo imaging system. AkaBLI produced emissions in vivo that were brighter by a factor of 100 to 1000 than conventional systems, allowing noninvasive visualization of single cells deep inside freely moving animals. Single tumorigenic cells trapped in the mouse lung vasculature could be visualized...
February 23, 2018: Science
https://www.readbyqxmd.com/read/29418019/new-developments-in-genetic-rat-models-of-parkinson-s-disease
#17
REVIEW
Rose B Creed, Matthew S Goldberg
Preclinical research on Parkinson's disease has relied heavily on mouse and rat animal models. Initially, PD animal models were generated primarily by chemical neurotoxins that induce acute loss of dopaminergic neurons in the substantia nigra. On the discovery of genetic mutations causally linked to PD, mice were used more than rats to generate laboratory animals bearing PD-linked mutations because mutagenesis was more difficult in rats. Recent advances in technology for mammalian genome engineering and optimization of viral expression vectors have increased the use of genetic rat models of PD...
February 8, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29397558/glutamate-excitotoxicity-linked-to-spermine-oxidase-overexpression
#18
Stefano Pietropaoli, Alessia Leonetti, Chiara Cervetto, Arianna Venturini, Roberta Mastrantonio, Giulia Baroli, Tiziana Persichini, Marco Colasanti, Guido Maura, Manuela Marcoli, Paolo Mariottini, Manuela Cervelli
Excitotoxic stress has been associated with several different neurological disorders, and it is one of the main causes of neuronal degeneration and death. To identify new potential proteins that could represent key factors in excitotoxic stress and to study the relationship between polyamine catabolism and excitotoxic damage, a novel transgenic mouse line overexpressing spermine oxidase enzyme in the neocortex (Dach-SMOX) has been engineered. These transgenic mice are more susceptible to excitotoxic injury and display a higher oxidative stress, highlighted by 8-Oxo-2'-deoxyguanosine increase and activation of defense mechanisms, as demonstrated by the increase of nuclear factor erythroid 2-related factor 2 (Nrf-2) in the nucleus...
February 3, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29378824/chromosomal-instability-during-neurogenesis-in-huntington-s-disease
#19
Albert Ruzo, Gist F Croft, Jakob J Metzger, Szilvia Galgoczi, Lauren J Gerber, Cecilia Pellegrini, Hanbin Wang, Maria Fenner, Stephanie Tse, Adam Marks, Corbyn Nchako, Ali H Brivanlou
Huntington's disease (HD) is a fatal neurodegenerative disease caused by expansion of CAG repeats in the Huntingtin gene ( HTT ). Neither its pathogenic mechanisms nor the normal functions of HTT are well understood. To model HD in humans, we engineered a genetic allelic series of isogenic human embryonic stem cell (hESC) lines with graded increases in CAG repeat length. Neural differentiation of these lines unveiled a novel developmental HD phenotype: the appearance of giant multinucleated telencephalic neurons at an abundance directly proportional to CAG repeat length, generated by a chromosomal instability and failed cytokinesis over multiple rounds of DNA replication...
January 29, 2018: Development
https://www.readbyqxmd.com/read/29371319/altered-baseline-and-nicotine-mediated-behavioral-and-cholinergic-profiles-in-chat-cre-mouse-lines
#20
Edison Chen, Valeria Lallai, Yasmine Sherafat, Nickolas P Grimes, Anna N Pushkin, J P Fowler, Christie D Fowler
The recent development of transgenic rodent lines expressing cre recombinase in a cell-specific manner, along with advances in engineered viral vectors, has permitted in-depth investigations into circuit function. However, emerging evidence has begun to suggest that genetic modifications may introduce unexpected caveats. In the current studies, we sought to extensively characterize male and female mice from both the ChAT(BAC) -Cre mouse line, created with the bacterial artificial chromosome (BAC) method, and ChAT(IRES) -Cre mouse line, generated with the internal ribosome entry site (IRES) method...
February 28, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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