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Molecular and Cellular Neurosciences

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https://www.readbyqxmd.com/read/29128320/exercise-decreases-bace-and-app-levels-in-the-hippocampus-of-a-rat-model-of-alzheimer-s-disease
#1
Karim A Alkadhi, An T Dao
We investigated the effect of treadmill exercise training on the levels of Alzheimer's disease (AD)-related protein molecules in the DG and CA1 areas of a rat model of AD, i.c.v. infusion of Aβ1-42 peptide, 2weeks (250pmol/day). Aβ infusion markedly increased protein levels of amyloid precursor protein (APP), the secretase beta-site APP cleaving enzyme-1 (BACE-1) and Aβ in the CA1 and DG areas. The results also revealed that 4weeks of treadmill exercise prevented the increase in the levels of APP, BACE-1 and Aβ proteins in both hippocampal areas...
November 9, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29128319/a-proteomic-investigation-into-mechanisms-underpinning-corticosteroid-effects-on-neural-stem-cells
#2
Rawaa S Al-Mayyahi, Luke D Sterio, Joanne B Connolly, Christopher F Adams, Wa'il A Al-Tumah, Jon Sen, Richard D Emes, Sarah R Hart, Divya M Chari
Corticosteroids (CSs) are widely used clinically, for example in pediatric respiratory distress syndrome, and immunosuppression to prevent rejection of stem cell transplant populations in neural cell therapy. However, such treatment can be associated with adverse effects such as impaired neurogenesis and myelination, and increased risk of cerebral palsy. There is increasing evidence that CSs can adversely influence key biological properties of neural stem cells (NSCs) but the molecular mechanisms underpinning such effects are largely unknown...
November 8, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29104140/low-dose-%C3%AE-secretase-inhibition-increases-secretion-of-a%C3%AE-peptides-and-intracellular-oligomeric-a%C3%AE
#3
Lotta Agholme, Marcus Clarin, Eleni Gkanatsiou, Petronella Kettunen, Jasmine Chebli, Gunnar Brinkmalm, Kaj Blennow, Petra Bergström, Erik Portelius, Henrik Zetterberg
γ-Secretase inhibitors have been considered promising drug candidates against Alzheimer's disease (AD) due to their ability to reduce amyloid-β (Aβ) production. However, clinical trials have been halted due to lack of clinical efficacy and/or side effects. Recent in vitro studies suggest that low doses of γ-secretase inhibitors may instead increase Aβ production. Using a stem cell-derived human model of cortical neurons and low doses of the γ-secretase inhibitor DAPT, the effects on a variety of Aβ peptides were studied using mass spectrometry...
November 8, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29122705/age-related-changes-in-striatal-enriched-protein-tyrosine-phosphatase-levels-regulation-by-bdnf
#4
Silvia Cases, Ana Saavedra, Shiraz Tyebji, Albert Giralt, Jordi Alberch, Esther Pérez-Navarro
Recent results indicate that STriatal-Enriched protein tyrosine Phosphatase (STEP) levels are regulated by brain-derived neurotrophic factor (BDNF), whose expression changes during postnatal development and aging. Here, we studied STEP ontogeny in mouse brain and changes in STEP with age with emphasis on the possible regulation by BDNF. We found that STEP expression increased during the first weeks of life, reaching adult levels by 2-3weeks of age in the striatum and cortex, and by postnatal day (P) 7 in the hippocampus...
November 6, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29122704/comparing-the-different-response-of-pns-and-cns-injured-neurons-to-mesenchymal-stem-cell-treatment
#5
Marianna Monfrini, Maddalena Ravasi, Daniele Maggioni, Elisabetta Donzelli, Giovanni Tredici, Guido Cavaletti, Arianna Scuteri
Mesenchymal stem cells (MSCs) are adult bone marrow-derived stem cells actually proposed indifferently for the therapy of neurological diseases of both the Central (CNS) and the Peripheral Nervous System (PNS), as a panacea able to treat so many different diseases by their immunomodulatory ability and supportive action on neuronal survival. However, the identification of the exact mechanism of MSC action in the different diseases, although mandatory to define their real and concrete utility, is still lacking...
November 6, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29113959/age-related-epigenetic-changes-in-hippocampal-subregions-of-four-animal-models-of-alzheimer-s-disease
#6
Roy Lardenoije, Daniël L A van den Hove, Monique Havermans, Anne van Casteren, Kevin X Le, Roberta Palmour, Cynthia A Lemere, Bart P F Rutten
Both aging and Alzheimer's disease (AD) are associated with widespread epigenetic changes, with most evidence suggesting global hypomethylation in AD. It is, however, unclear how these age-related epigenetic changes are linked to molecular aberrations as expressed in animal models of AD. Here, we investigated age-related changes of epigenetic markers of DNA methylation and hydroxymethylation in a range of animal models of AD, and their correlations with amyloid plaque load. Three transgenic mouse models, including the J20, APP/PS1dE9 and 3xTg-AD models, as well as Caribbean vervets (a non-transgenic non-human primate model of AD) were investigated...
November 4, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29109020/an-immortalized-microglial-cell-line-mocha-derived-from-rat-cochlea
#7
G M Seigel, S Manohar, Y Y Bai, D Ding, R Salvi
Microglia are glial-immune cells that are essential for the function and survival of the central nervous system. Microglia not only protect neural tissues from immunological insults, but also play a critical role in neural development and repair. However, little is known about the biology of microglia in the cochlea, the auditory portion of the inner ear. In this study, we detected TMEM119+, CD11b+, CD45+ and Iba1+ populations of cells in the rat cochlea, particularly in Rosenthal's canal, inner sulcus and stria vascularis...
November 3, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29107098/corticosteroid-induced-dendrite-loss-and-behavioral-deficiencies-can-be-blocked-by-activation-of-abl2-arg-kinase
#8
Lauren P Shapiro, Mitchell H Omar, Anthony J Koleske, Shannon L Gourley
Stressor exposure induces neuronal remodeling in specific brain regions. Given the persistence of stress-related illnesses, key next steps in determining the contributions of neural structure to mental health are to identify cell types that fail to recover from stressor exposure and to identify "trigger points" and molecular underpinnings of stress-related neural degeneration. We evaluated dendrite arbor structure on hippocampal CA1 pyramidal neurons before, during, and following prolonged exposure to one key mediator of the stress response - corticosterone (cortisol in humans)...
October 26, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29079539/study-of-the-in-vitro-modulation-exerted-by-the-antidepressant-drug-escitalopram-on-the-expression-of-candidate-micrornas-and-their-target-genes
#9
Elisabetta Maffioletti, Alessandro Salvi, Isabel Conde, Carlo Maj, Massimo Gennarelli, Giuseppina De Petro, Luisella Bocchio-Chiavetto
Recent studies indicated a role of microRNAs (miRNAs, small non-coding RNAs which regulate the expression of target genes by acting on mRNAs) in several neural processes, in the pathogenetic mechanisms of neuropsychiatric diseases and in the action of psychotropic drugs. A modulation induced by the antidepressant drug escitalopram on the expression levels of 30 miRNAs was highlighted in the blood of patients suffering from major depressive disorder. With the aim to investigate the effects of escitalopram in an in vitro model, we performed an analysis of the effects produced by escitalopram on the profiles of the 6 miRNAs found to be more significantly modulated in the above-mentioned study (miR-130b, miR-26a and -26b, let-7f, miR-770-5p, miR-34c-5p) in human U87 glioblastoma cells...
October 25, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29066292/rem2-signaling-affects-neuronal-structure-and-function-in-part-by-regulation-of-gene-expression
#10
Katelyn Kenny, Leandro Royer, Anna R Moore, Xiao Chen, Michael T Marr, Suzanne Paradis
The central nervous system has the remarkable ability to convert changes in the environment in the form of sensory experience into long-term alterations in synaptic connections and dendritic arborization, in part through changes in gene expression. Surprisingly, the molecular mechanisms that translate neuronal activity into changes in neuronal connectivity and morphology remain elusive. Rem2, a member of the Rad/Rem/Rem2/Gem/Kir (RGK) subfamily of small Ras-like GTPases, is a positive regulator of synapse formation and negative regulator of dendritic arborization...
October 21, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29055697/cocaine-alters-homer1-natural-antisense-transcript-in-the-nucleus-accumbens
#11
Gregory C Sartor, Samuel K Powell, Dmitry Velmeshev, David Y Lin, Marco Magistri, Hannah J Wiedner, Andrea M Malvezzi, Nadja S Andrade, Mohammad A Faghihi, Claes Wahlestedt
Natural antisense transcripts (NATs) are an abundant class of long noncoding RNAs that have recently been shown to be key regulators of chromatin dynamics and gene expression in nervous system development and neurological disorders. However, it is currently unclear if NAT-based mechanisms also play a role in drug-induced neuroadaptations. Aberrant regulation of gene expression is one critical factor underlying the long-lasting behavioral abnormalities that characterize substance use disorder, and it is possible that some drug-induced transcriptional responses are mediated, in part, by perturbations in NAT activity...
October 18, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29017814/pituitary-adenylate-cyclase-activating-polypeptide-induces-long-term-transcription-dependent-plasticity-and-remodeling-at-autonomic-synapses
#12
Eric R Starr, Joseph F Margiotta
Pituitary adenylate cyclase activating polypeptide (PACAP) is a multifunctional neuropeptide, widely expressed in the nervous system (Vaudry et al., 2009; Starr and Margiotta, 2016). At neuronal synapses where transmission is mediated by nicotinic acetylcholine receptors (nAChRs) transient PACAP exposure increases the frequency and amplitude (FS and AS) of spontaneous excitatory postsynaptic currents (sEPSCs) within minutes. This short-term (ST) plasticity requires high-affinity PACAP receptor (PAC1R) signaling via adenylate cyclase (AC), cyclic AMP (cAMP), Protein kinase A (PKA) and obligatory nAChR-dependent stimulation of nitric oxide (NO) synthesis to retrogradely increase presynaptic ACh release (Pugh et al...
October 7, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28989002/chi3l1-and-chi3l2-overexpression-in-motor-cortex-and-spinal-cord-of-sals-patients
#13
C Sanfilippo, A Longo, F Lazzara, D Cambria, G Distefano, M Palumbo, A Cantarella, L Malaguarnera, M Di Rosa
BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive neurodegenerative disease characterized by the degeneration and death of upper (UMN) and lower (LMN) motor neurons. In the last decade, it has been shown that Chitinases are an important prognostic indicator of neuro-inflammatory damage induced by microglia and astrocytes. MATERIALS AND METHODS: We analyzed microarray datasets obtained from the Array Express in order to verify the expression levels of CHI3L1 and CHI3L2 in motor cortex biopsies of sALS patients with different survival times...
October 6, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28974382/dual-effect-of-serotonin-on-the-dendritic-growth-of-cultured-hippocampal-neurons-involvement-of-5-ht1a-and-5-ht7-receptors
#14
P S Rojas, F Aguayo, D Neira, M Tejos, E Aliaga, J P Muñoz, C S Parra, J L Fiedler
Serotonin acts through its receptors (5-HTRs) to shape brain networks during development and modulates essential functions in mature brain. The 5-HT1AR is mainly located at soma of hippocampal neurons early during brain development and its expression gradually shifts to dendrites during postnatal development. The 5-HT7R expressed early during hippocampus development, shows a progressive reduction in its expression postnatally. Considering these changes during development, we evaluated in cultured hippocampal neurons whether the 5-HT1AR and 5-HT7R change their expression, modulate dendritic growth, and activate signaling pathways such as ERK1/2, AKT/GSK3β and LIMK/cofilin, which may sustain dendrite outgrowth by controlling cytoskeleton dynamics...
September 30, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28966131/ras-grf2-regulates-nestin-positive-stem-cell-density-and-onset-of-differentiation-during-adult-neurogenesis-in-the-mouse-dentate-gyrus
#15
Carmela Gómez, David Jimeno, Alberto Fernández-Medarde, Rósula García-Navas, Nuria Calzada, Eugenio Santos
Various parameters of neurogenesis were analyzed in parallel in the two neurogenic areas (the Dentate Gyrus[DG] and the Subventricular Zone[SVZ]/Rostral Migratory Stream[RMS]/Main Olfactory Bulb[MOB] neurogenic system) of adult WT and KO mouse strains for the Ras-GRF1/2 genes (Ras-GRF1-KO, Ras-GRF2-KO, Ras-GRF1/2-DKO). Significantly reduced numbers of doublecortin[DCX]-positive cells were specifically observed in the DG, but not the SVZ/RMS/MOB neurogenic region, of Ras-GRF2-KO and Ras-GRF1/2-DKO mice indicating that this novel Ras-GRF2-dependent phenotype is spatially restricted to a specific neurogenic area...
September 28, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28942046/chronic-ethanol-exposure-increases-inhibition-of-optically-targeted-phasic-dopamine-release-in-the-nucleus-accumbens-core-and-medial-shell-ex-vivo
#16
James R Melchior, Sara R Jones
Dopamine signaling encodes reward learning and motivated behavior through modulation of synaptic signaling in the nucleus accumbens, and aberrations in these processes are thought to underlie obsessive behaviors associated with alcohol abuse. The nucleus accumbens is divided into core and shell sub-regions with overlapping but also divergent contributions to behavior. Here we optogenetically targeted dopamine projections to the accumbens allowing us to isolate stimulation of dopamine terminals ex vivo. We applied 5 pulse (phasic) light stimulations to probe intrinsic differences in dopamine release parameters across regions...
September 20, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28939329/potential-deficit-from-decreased-cerebellar-granule-cell-migration-in-serine-racemase-deficient-mice-is-reversed-by-increased-expression-of-glun2b-and-elevated-levels-of-nmdar-agonists
#17
He Zhang, Liping Song, Yuhua Chang, Mengjuan Wu, Xiuli Kuang, Haiyan Jiang, Shengzhou Wu
Inward migration of cerebellar granule cells (CGCs) after birth is critical for lamination in the cerebellar cortex. N-methyl-d-aspartate (NMDA) subtype of glutamate receptor (NMDAR) tethering CGCs into Bergmann glial fibers mediates the inward movement during the glial-dependent migratory phase. Activation of NMDAR depends on simultaneous binding of the GluN2 subunit by glutamate, and of the GluN1 subunit by d-serine or glycine; d-serine is believed to be an endogenous ligand of NMDAR. We hypothesized that lamination of the cerebellar cortex may be compromised in Srr (the gene for serine racemase (SR)) mutated mice (Srrnull) because of significantly low levels of d-serine per se...
September 20, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28923595/attentional-deficits-and-altered-neuronal-activation-in-medial-prefrontal-and-posterior-parietal-cortices-in-mice-with-reduced-dopamine-transporter-levels
#18
Anita Cybulska-Klosowicz, Marta Laczkowska, Renata Zakrzewska, Aleksandra Kaliszewska
The executive control function of attention is regulated by the dopaminergic (DA) system. Dopamine transporter (DAT) likely plays a role in controlling the influence of DA on cognitive processes. We examined the effects of DAT depletion on cognitive processes related to attention. Mice with the DAT gene genetically deleted (DAT+/- heterozygotes) were compared to wild type (WT) mice on the Attentional Set-Shifting Task (ASST). Changes in neuronal activity during the ASST were shown with early growth response genes 1 and 2 (egr-1 and egr-2) immunohistochemistry in the medial prefrontal cortex (mPFC) and in the posterior parietal cortex (PPC)...
September 18, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28889993/a-subpopulation-of-activated-retinal-macrophages-selectively-migrated-to-regions-of-cone-photoreceptor-stress-but-had-limited-effect-on-cone-death-in-a-mouse-model-for-type-2-leber-congenital-amaurosis
#19
Peter H Tang, Mark J Pierson, Neal D Heuss, Dale S Gregerson
BACKGROUND: Studies of antigen presentation in retina using mice that expressed green fluorescent protein (GFP) from a transgenic CD11c promoter found that retinal GFP(hi) cells possessed antigen presentation function. Subsequent studies found that these high GFP(hi) cells preferentially localized to sites of retinal injury, consistent with their APC function. Interest in the roles of macrophages in degenerative CNS diseases led us to study the GFP(hi) cells in a retinal model of neurodegeneration...
September 8, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28889992/astrocytic-expression-of-the-cxcl12-receptor-cxcr7-ackr3-is-a-hallmark-of-the-diseased-but-not-developing-cns
#20
Malte Puchert, Fabian Pelkner, Gregor Stein, Doychin N Angelov, Johannes Boltze, Daniel-Christoph Wagner, Francesca Odoardi, Alexander Flügel, Wolfgang J Streit, Jürgen Engele
Based on our previous demonstration of CXCR7 as the major mediator of CXCL12 signaling in cultured astrocytes, we have now compared astrocytic expression of the CXCL12 receptors, CXCR7 and CXCR4, during CNS development and disease. In addition, we asked whether disease-associated conditions/factors affect expression of CXCL12 receptors in astrocytes. In the late embryonic rat brain, CXCR7(+)/GFAP(+) cells were restricted to the ventricular/subventricular zone while CXCR4 was widely absent from GFAP-positive cells...
September 8, 2017: Molecular and Cellular Neurosciences
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