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https://www.readbyqxmd.com/read/28645186/igf-i-gene-therapy-in-aging-rats-modulates-hippocampal-genes-relevant-to-memory-function
#1
Joaquín Pardo, Martin C Abba, Ezequiel Lacunza, Olalekan M Ogundele, Isabel Paiva, Gustavo R Morel, Tiago F Outeiro, Rodolfo G Goya
In rats, learning and memory performance decline during normal aging, which makes this rodent species a suitable model to evaluate therapeutic strategies. In aging rats, insulin-like growth factor-I (IGF-I), is known to significantly improve spatial memory accuracy as compared to control counterparts. A constellation of gene expression changes underlie the hippocampal phenotype of aging but no studies on the effects of IGF-I on the hippocampal transcriptome of old rodents have been documented. Here, we assessed the effects of IGF-I gene therapy on spatial memory performance in old female rats and compared them with changes in the hippocampal transcriptome...
June 22, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28645106/phorbol-esters-dppa-dpa-promote-furin-expression-involving-transcription-factor-cebp%C3%AE-in-neuronal-cells
#2
Jing-Si Zha, Bing-Lin Zhu, Lu Liu, Yu-Jie Lai, Yan Long, Xiao-Tong Hu, Xiao-Juan Deng, Xue-Feng Wang, Zhen Yan, Guo-Jun Chen
Using high-throughput small molecule screening targeting furin gene, we identified that phorbol esters dPPA (12-Deoxyphorbol 13-phenylacetate 20-acetate) and dPA (12-Deoxyphorbol 13-acetate) significantly increased furin protein and mRNA expression in SH-SY5Y cells. This effect was prevented by PKC (protein kinase C) inhibitor calphostin C but not Ro318220, suggesting that the C1 domain, rather than the catalytic domain of PKC plays an important role. Luciferase assay revealed that nucleotides -7925 to -7426 were sufficient to mediate dPPA/dPA enhancement of furin P1 promoter activity...
June 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28645069/controlled-single-bubble-cavitation-collapse-results-in-jet-induced-injury-in-brain-tissue
#3
Saranya Canchi, Karen Kelly, Yu Hong, Michael A King, Ghatu Subhash, Malisa Sarntinoranont
Multiscale damage due to cavitation is considered as a potential mechanism of traumatic brain injury (TBI) associated with explosion. In this study, we employed a TBI relevant hippocampal ex vivo slice model to induce bubble cavitation. Placement of single reproducible seed bubbles allowed control of size, number, and tissue location to visualize and measure deformation parameters. Maximum strain value was measured at 45 µs after bubble collapse, presented with a distinct contour and coincided temporally and spatially with the liquid jet...
June 15, 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/28645005/application-of-stem-cell-derived-neuronal-cells-to-evaluate-neurotoxic-chemotherapy
#4
Claudia Wing, Masaaki Komatsu, Shannon M Delaney, Matthew Krause, Heather E Wheeler, M Eileen Dolan
The generation of induced pluripotent stem cells (iPSCs) and differentiation to cells composing major organs has opened up the possibility for a new model system to study adverse toxicities associated with chemotherapy. Therefore, we used human iPSC-derived neurons to study peripheral neuropathy, one of the most common adverse effects of chemotherapy and cause for dose reduction. To determine the utility of these neurons in investigating the effects of neurotoxic chemotherapy, we measured morphological differences in neurite outgrowth, cell viability as determined by ATP levels and apoptosis through measures of caspase 3/7 activation following treatment with clinically relevant concentrations of platinating agents (cisplatin, oxaliplatin and carboplatin), taxanes (paclitaxel, docetaxel and nab-paclitaxel), a targeted proteasome inhibitor (bortezomib), an antiangiogenic compound (thalidomide), and 5-fluorouracil, a chemotherapeutic that does not cause neuropathy...
June 15, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28644911/interictal-oscillations-and-focal-epileptic-disorders
#5
Maxime Lévesque, Pariya Salami, Zahra Shiri, Massimo Avoli
Neuronal network oscillations represent a main feature of the brain activity recorded in the EEG under normal and pathological conditions such as epilepsy. Specific oscillations occur between seizures in patients and in animal models of focal epilepsy, and thus they are termed interictal. According to their shape and intrinsic signal frequency, interictal oscillations are classified as spikes and high frequency oscillations (HFOs). Interictal spikes are recorded in the "wideband" EEG signal and consist of large-amplitude events that usually last less than 1 s; HFOs, in contrast, are extracted by amplifying the appropriately filtered EEG signal, and are usually categorized as ripples (80-200 Hz) and fast ripples (250-500 Hz)...
June 23, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28644906/cholinesterases-in-normal-and-alzheimer-s-disease-primary-olfactory-gyrus
#6
Hayam Hamodat, Meghan K Cash, John D Fisk, Sultan Darvesh
AIMS: Alzheimer's disease (AD) is characterized by cholinergic dysfunction and deposition of β-amyloid (Aβ) plaques and tau neurofibrillary tangles (NFTs) in the brain. Olfactory abnormalities often precede cognitive symptoms in AD, indicating early involvement of pathology in olfactory structures. The cholinergic system is important not only in cognition but also in modulation of the olfactory system. The primary olfactory gyrus (POG) is comprised of the olfactory tract, anterior olfactory nucleus (AON) and olfactory area (OA)...
June 23, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/28644902/sirt6-alters-adult-hippocampal-neurogenesis
#7
Eitan Okun, Daniel Marton, Daniel Cohen, Kathleen Griffioen, Yariv Kanfi, Tomer Illouz, Ravit Madar, Haim Y Cohen
Sirtuins are pleiotropic NAD+ dependent histone deacetylases involved in metabolism, DNA damage repair, inflammation and stress resistance. SIRT6, a member of the sirtuin family, regulates the process of normal aging and increases the lifespan of male mice over-expressing Sirt6 by 15%. Neurogenesis, the formation of new neurons within the hippocampus of adult mammals, involves several complex stages including stem cell proliferation, differentiation, migration and network integration. During aging, the number of newly generated neurons continuously declines, and this is correlated with a decline in neuronal plasticity and cognitive behavior...
2017: PloS One
https://www.readbyqxmd.com/read/28644841/low-dimensional-spike-rate-models-derived-from-networks-of-adaptive-integrate-and-fire-neurons-comparison-and-implementation
#8
Moritz Augustin, Josef Ladenbauer, Fabian Baumann, Klaus Obermayer
The spiking activity of single neurons can be well described by a nonlinear integrate-and-fire model that includes somatic adaptation. When exposed to fluctuating inputs sparsely coupled populations of these model neurons exhibit stochastic collective dynamics that can be effectively characterized using the Fokker-Planck equation. This approach, however, leads to a model with an infinite-dimensional state space and non-standard boundary conditions. Here we derive from that description four simple models for the spike rate dynamics in terms of low-dimensional ordinary differential equations using two different reduction techniques: one uses the spectral decomposition of the Fokker-Planck operator, the other is based on a cascade of two linear filters and a nonlinearity, which are determined from the Fokker-Planck equation and semi-analytically approximated...
June 23, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28644840/linking-structure-and-activity-in-nonlinear-spiking-networks
#9
Gabriel Koch Ocker, Krešimir Josić, Eric Shea-Brown, Michael A Buice
Recent experimental advances are producing an avalanche of data on both neural connectivity and neural activity. To take full advantage of these two emerging datasets we need a framework that links them, revealing how collective neural activity arises from the structure of neural connectivity and intrinsic neural dynamics. This problem of structure-driven activity has drawn major interest in computational neuroscience. Existing methods for relating activity and architecture in spiking networks rely on linearizing activity around a central operating point and thus fail to capture the nonlinear responses of individual neurons that are the hallmark of neural information processing...
June 23, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28644712/comparative-analysis-of-behavioral-and-transcriptional-variation-underlying-co2-sensory-neuron-function-and-development-in-drosophila
#10
Jia Wern Pan, Joi McLaughlin, Haining Yang, Charles Leo, Paula Rambarat, Sumie Okuwa, Anaïs Monroy-Eklund, Sabrina Clark, Corbin D Jones, Pelin Cayirlioglu Volkan
Carbon dioxide is an important environmental cue for many insects, regulating many behaviors including some that have direct human impacts. To further improve our understanding of how this system varies among closely related insect species, we examined both the behavioral response to CO2 as well as the transcriptional profile of key developmental regulators of CO2 sensory neurons in the olfactory system across the Drosophila genus. We found that CO2 generally evokes repulsive behavior across most of the Drosophilids we examined, but this behavior has been lost or reduced in several lineages...
June 23, 2017: Fly
https://www.readbyqxmd.com/read/28644439/activation-of-cell-surface-grp78-decreases-endoplasmic-reticulum-stress-and-neuronal-death
#11
Morgane Louessard, Isabelle Bardou, Eloïse Lemarchand, Audrey M Thiebaut, Jérôme Parcq, Jérôme Leprince, Anne Terrisse, Valérie Carraro, Pierre Fafournoux, Alain Bruhat, Cyrille Orset, Denis Vivien, Carine Ali, Benoit D Roussel
The unfolded protein response (UPR) is an endoplasmic reticulum (ER) -related stress conserved pathway that aims to protect cells from being overwhelmed. However, when prolonged, UPR activation converts to a death signal, which relies on its PERK-eIF2α branch. Overactivation of the UPR has been implicated in many neurological diseases, including cerebral ischaemia. Here, by using an in vivo thromboembolic model of stroke on transgenic ER stress-reporter mice and neuronal in vitro models of ischaemia, we demonstrate that ischaemic stress leads to the deleterious activation of the PERK branch of the UPR...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644437/more-alive-than-dead-non-apoptotic-roles-for-caspases-in-neuronal-development-plasticity-and-disease
#12
REVIEW
Amrita Mukherjee, Darren W Williams
Nervous systems are arguably the most fascinating and complex structures in the known universe. How they are built, changed by experience and then degenerate are some of the biggest questions in biology. Regressive phenomena, such as neuron pruning and programmed cell death, have a key role in the building and maintenance of the nervous systems. Both of these cellular mechanisms deploy the caspase family of protease enzymes. In this review, we highlight the non-apoptotic function of caspases during nervous system development, plasticity and disease, particularly focussing on their role in structural remodelling...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644430/the-clinical-landscape-for-sma-in-a-new-therapeutic-era
#13
REVIEW
K Talbot, E F Tizzano
Despite significant advances in basic research, the treatment of degenerative diseases of the nervous system remains one of the greatest challenges for translational medicine. The childhood onset motor neuron disorder spinal muscular atrophy (SMA) has been viewed as one of the more tractable targets for molecular therapy, due to a detailed understanding of the molecular genetic basis of the disease. In SMA, inactivating mutations in the SMN1 gene can be partially compensated for by limited expression of SMN protein from a variable number of copies of the SMN2 gene, which provides both a molecular explanation for phenotypic severity and a target for therapy...
June 23, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28644417/herpes-simplex-virus-establishment-maintenance-and-reactivation-in-vitro-modeling-of-latency
#14
REVIEW
Nikki M Thellman, Steven J Triezenberg
All herpes viruses establish lifelong infections (latency) in their host, and herpes simplex viruses (HSVs) are highly prevalent worldwide. Recurrence of HSV infections contributes to significant disease burden in people and on rare occasion can be fatal. Cell culture models that recapitulate latent infection provide valuable insight on the host processes regulating viral establishment and maintenance of latency. More robust and rapid than infections in live animal studies, advancements in neuronal culture techniques have made the systematic analysis of viral reactivation mechanisms feasible...
June 23, 2017: Pathogens
https://www.readbyqxmd.com/read/28644111/visual-dot-interaction-with-short-term-memory
#15
Faustin Armel Etindele Sosso
AIM: Many neurodegenerative diseases have a memory component. Brain structures related to memory are affected by environmental stimuli, and it is difficult to dissociate effects of all behavior of neurons. MATERIALS & METHODS: Here, visual cortex of mice was stimulated with gratings and dot, and an observation of neuronal activity before and after was made. Bandwidth, firing rate and orientation selectivity index were evaluated. RESULTS: A primary communication between primary visual cortex and short-term memory appeared to show an interesting path to train cognitive circuitry and investigate the basics mechanisms of the neuronal learning...
June 23, 2017: Neurodegenerative Disease Management
https://www.readbyqxmd.com/read/28644021/synthesis-of-11-o-debenzoyltashironin-neurotrophic-sesquiterpenes-cause-hyperexcitation
#16
Masaki Ohtawa, Michael J Krambis, Rok Cerne, Jeffrey M Schkeryantz, Jeffrey Witkin, Ryan A Shenvi
11-O-Debenzoyltashironin (1) is a member of the neurotrophic sesquiterpenes, trace plant metabolites that enhance neurite outgrowth in cultured neurons. Here we report its synthesis in six steps from a butenolide heterodimer via its likely biosynthetic precursor, 3,6-dideoxy-10-hydroxypseudoanisatin, here identified as the chain tautomer of 1. Access to the tashironin chemotype fills a gap in a comparison set of convulsive and neurotrophic sesquiterpenes, which we hypothesized to share a common target. Here we show that both classes mutually hyperexcite rat cortical neurons, consistent with antagonism of inhibitory channels...
June 23, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28644012/sigma-2-receptor-tmem97-agonists-produce-long-lasting-anti-neuropathic-pain-effects-in-mice
#17
James J Sahn, Galo L Mejia, Pradipta R Ray, Stephen F Martin, Theodore John Price
Neuropathic pain is an important medical problem with few effective treatments. The sigma 1 receptor (σ1R) is a potential target for neuropathic pain therapeutics, and antagonists for this receptor are effective in preclinical models and are currently in phase II clinical trials. Relatively little is known about the σ2R, which has recently been identified as transmembrane protein 97 (Tmem97). We generated a series of σ1R and σ2R/Tmem97 agonists and antagonists and tested them for efficacy in the mouse spared nerve injury (SNI) model...
June 23, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28643952/asn194lys-mutation-in-rvg29-peptide-increases-gfp-transgene-delivery-by-endocytosis-to-neuroblastoma-and-astrocyte-cells
#18
Sheila Adela Villa-Cedillo, Humberto Rodríguez-Rocha, Laura Mireya Zavala-Flores, Roberto Montes-de-Oca-Luna, Aracely García-García, Maria de Jesus Loera-Arias, Odila Saucedo-Cárdenas
OBJECTIVES: A cell-penetrating peptide-based delivery system could target specific types of cells for therapeutic genes delivery. To increase the gene delivery efficiency into neuronal phenotype cells, we introduced an Asn194Lys mutation to RVG29 peptide derived from rabies virus glycoprotein and added a nuclear localization signal to enhance its nuclear import. METHODS: Mutant RVG or wild-type RVG peptide, a karyophilic peptide (KP) and a plasmid encoding green fluorescent protein (pGL) were bound by electrostatic charges to form four different kinds of RVG complexes...
June 23, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28643927/co2-low-level-laser-therapy-has-an-early-but-not-delayed-pain-effect-during-experimental-tooth-movement
#19
T Deguchi, D G Kim, H Kamioka
OBJECTIVES: To test the hypothesis that the use of low-level laser therapy (LLLT) reduces elevated pain by controlling the release of neurochemicals during orthodontic tooth movement. SETTING AND SAMPLE POPULATION: Department of Orthodontics and Dentofacial Orthopedics, Okayama University. Sixty-five Sprague Dawley rats were subjected to tooth movement and LLLT. MATERIALS AND METHODS: Adult Sprague Dawley rats were used in this study. Groups included day 0 controls, irradiation only controls and with or without irradiation sacrificed at 1, 3, 5, 7 and 14 days after tooth movement (n=5 each, total n=65)...
June 2017: Orthodontics & Craniofacial Research
https://www.readbyqxmd.com/read/28643873/increased-expression-of-immuno-proteasome-subunits-during-epileptogenesis-is-attenuated-by-inhibition-of-the-mammalian-target-of-rapamycin-pathway
#20
Diede W M Broekaart, Jackelien van Scheppingen, Karlijne W Geijtenbeek, Mark R J Zuidberg, Jasper J Anink, Johannes C Baayen, Angelika Mühlebner, Eleonora Aronica, Jan A Gorter, Erwin A van Vliet
OBJECTIVE: Inhibition of the mammalian target of rapamycin (mTOR) pathway reduces epileptogenesis in various epilepsy models, possibly by inhibition of inflammatory processes, which may include the proteasome system. To study the role of mTOR inhibition in the regulation of the proteasome system, we investigated (immuno)proteasome expression during epileptogenesis, as well as the effects of the mTOR inhibitor rapamycin. METHODS: The expression of constitutive (β1, β5) and immunoproteasome (β1i, β5i) subunits was investigated during epileptogenesis using immunohistochemistry in the electrical post-status epilepticus (SE) rat model for temporal lobe epilepsy (TLE)...
June 23, 2017: Epilepsia
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