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Molecular and Cellular Neurosciences

Joseph E Pick, Edward B Ziff
A fundamental property of the brain is its ability to modify its function in response to its own activity. This ability for self-modification depends to a large extent on synaptic plasticity. It is now appreciated that for excitatory synapses, a significant part of synaptic plasticity depends upon changes in the post synaptic response to glutamate released from nerve terminals. Modification of the post synaptic response depends, in turn, on changes in the abundances of AMPA receptors in the post synaptic membrane...
March 12, 2018: Molecular and Cellular Neurosciences
T Gabriel Enge, Heath Ecroyd, Dianne F Jolley, Justin J Yerbury, Bernadett Kalmar, Anthony Dosseto
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is among the most common of the motor neuron diseases, and arguably the most devastating. During the course of this fatal neurodegenerative disorder, motor neurons undergo progressive degeneration. The currently best-understood animal models of ALS are based on the over-expression of mutant isoforms of Cu/Zn superoxide dismutase 1 (SOD1); these indicate that there is a perturbation in metal homeostasis with disease progression. Copper metabolism in particular is affected in the central nervous system (CNS) and muscle tissue...
March 7, 2018: Molecular and Cellular Neurosciences
Lina A Matschke, Susanne Rinné, Terrance P Snutch, Wolfgang H Oertel, Amalia M Dolga, Niels Decher
The physiological, intrinsic activity of noradrenergic locus coeruleus (LC) neurons is important for the control of sleep/wakefulness, cognition and autonomous body functions. Dysregulations of the LC-noradrenergic network contribute to the pathogenesis of psychiatric disorders and are key findings in early stages of neurodegenerative diseases. Therefore, identifying ion channels mediating the intrinsic pacemaking mechanism of LC neurons, which is in turn directly coupled to Ca2+ homeostasis and cell survival signaling pathways, can help to foster our understanding of the vulnerability of these neurons in neurodegenerative diseases...
March 7, 2018: Molecular and Cellular Neurosciences
Kevin S O'Connell, Nathaniel W McGregor, Christine Lochner, Robin Emsley, Louise Warnich
Considerable evidence suggests that autism spectrum disorders (ASD), schizophrenia (SCZ), bipolar disorder (BD) and obsessive-compulsive disorder (OCD) share a common molecular aetiology, despite their unique clinical diagnostic criteria. The aim of this study was therefore to determine and characterise the common and unique molecular architecture of ASD, SCZ, BD and OCD. Gene lists were obtained from previously published studies for ASD, BD, SCZ and for OCD. Genes identified to be common to all disorders, or unique to one specific disorder, were included for enrichment analyses using the web-server tool Enrichr...
March 2, 2018: Molecular and Cellular Neurosciences
Tim Vanmierlo, Jochen De Vry, Ellis Nelissen, Annerieke Sierksma, Nadia Roumans, Harry W M Steinbusch, Lawrence P Wennogle, Daniel van den Hove, Jos Prickaerts
Stress during pregnancy increases the risk to develop psychological disorders such as depression during pregnancy or in the postpartum period. According to the neurotrophin hypothesis of depression, the pathophysiology of depression is caused by reduced neurotrophic activity in the brain. However, most studies only focus on the molecular changes happening to the offspring upon gestational stress. To gain insight into the potential molecular changes happening in the stressed dams, C57Bl6/J mice were stressed during their first week of gestation...
February 28, 2018: Molecular and Cellular Neurosciences
Rumana Akhter, Suraiya Saleem, Akash Saha, Subhas Chandra Biswas
The pro-apoptotic Bcl-2 homology 3 domain only (BH3-only) proteins are central regulators of cell death in various physiological and pathological conditions, including Alzheimer's disease (AD). Bcl-2 modifying factor (Bmf) is one such BH3-only protein that is implicated in various death paradigms such as anoikis, seizures, cancer and autoimmunity. It also co-operates with other BH3-only proteins such as Bim in various death paradigms. However, its role in neurodegeneration is under-investigated. Here, we report for the first time the essential role of Bmf and its co-operativity with direct activator BH3-only proteins Bim and Puma in neuron death induced by beta-amyloid (Aβ) toxicity or NGF deprivation...
February 27, 2018: Molecular and Cellular Neurosciences
T V Povysheva, Y O Mukhamedshina, A A Rizvanov, Y A Chelyshev
The role of the Rho/ROCK/PTEN signaling pathway in the regulation of astrocyte function for consolidation/stabilization of the synapse has not been thoroughly studied. In this study, the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in GFAP-positive astrocytic processes in the ventral horns (VH) of the rat spinal cord has been evaluated in the normal condition and in a delayed period (30 days) after dosed contusion spinal cord injury (SCI) in caudal thoracic segments. In intact rats and at 30 days post-injury (dpi), semi-quantitative immunohistochemical analysis showed that there is approximately 2 folds less synaptophysin reactivity in the motoneuron perikarya than outside the perikarya, i...
February 15, 2018: Molecular and Cellular Neurosciences
Andrea Beatriz Cragnolini, Gonzalo Montenegro, Wilma J Friedman, Daniel Hugo Mascó
Astrocytes are a heterogeneous population of glial cells that react to brain insults through a process referred to as astrogliosis. Reactive astrocytes are characterized by an increase in proliferation, size, migration to the injured zone and release of a plethora of chemical mediators such as NGF and BDNF. The aim of this study was to determine whether there are brain region-associated responses of astrocytes to an injury and to the neurotrophins NGF and BDNF. We used the scratch injury model to study the closure of a wound inflicted on a monolayer of astrocytes obtained from cortex, hippocampus or striatum...
February 11, 2018: Molecular and Cellular Neurosciences
Rosanna Avola, Adriana Carol Eleonora Graziano, Giovanna Pannuzzo, Ferdaous Albouchi, Venera Cardile
The purpose of this research was to explore the behavior of aquaporins (AQPs) in an in vitro model of Parkinson's disease that is a recurrent neurodegenerative disorder caused by the gradual, progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Because of postmortem studies have provided evidences for oxidative damage and alteration of water flow and energy metabolism, we carried out an investigation about AQP4 and 9, demonstrated in the brain to maintain water and energy homeostasis...
February 8, 2018: Molecular and Cellular Neurosciences
Shohreh Majd, Zohreh Majd, Simon Koblar, John Power
Hyperphosphorylation of tau is one of the main hallmarks for Alzheimer's disease (AD) and many other tauopathies. Norepinephrine (NE), a stress-related hormone 17-β-estradiol (E2) and thought to influence tau phosphorylation (p-tau) and AD pathology. The controversy around the impact of NE and E2 requires further clarification. Moreover, the combination effect of physiological and psychological stress and estrogen alteration during menopause, which affect p-tau, has not been addressed. Exposure to E2 is believed to reduce NE release, however, the link between these two hormones and AD at cellular level was also remained unknown...
February 7, 2018: Molecular and Cellular Neurosciences
Anna-Maria Holl
The main olfactory epithelium (MOE) of an adult mouse harbors a few million mature olfactory sensory neurons (OSNs), which are traditionally defined as mature by their expression of the olfactory marker protein (OMP). Mature OSNs differentiate in situ from stem cells at the base of the MOE. The consensus view is that mature OSNs have a defined lifespan and then undergo programmed cell death, and that the adult MOE maintains homeostasis by generating new mature OSNs from stem cells. But there is also evidence for mature OSNs that are long-lived...
February 7, 2018: Molecular and Cellular Neurosciences
Gergő Vőfély, Tünde Berecz, Eszter Szabó, Kornélia Szebényi, Edit Hathy, Tamás I Orbán, Balázs Sarkadi, László Homolya, Maria C Marchetto, János M Réthelyi, Ágota Apáti
Pluripotent stem cell derived human neuronal progenitor cells (hPSC-NPCs) and their mature neuronal cell culture derivatives may efficiently be used for central nervous system (CNS) drug screening, including the investigation of ligand-induced calcium signalization. We have established hippocampal NPC cultures derived from human induced PSCs, which were previously generated by non-integrating Sendai virus reprogramming. Using established protocols these NPCs were differentiated into hippocampal dentate gyrus neurons...
February 6, 2018: Molecular and Cellular Neurosciences
Bo Wang, Shuangshuang Han
Traumatic brain injury (TBI) has been associated with an increased risk for neurodegenerative diseases, and Tau spread and accumulation might be one of the mechanisms underlying this process. Exosomes were speculated to be a vehicle for spreading Tau in neurodegenerative diseases. The present study sought to investigate the effect of exosome associated Tau after TBI. C57BL/6J mice were subjected to controlled cortical impact injury and the levels of total and phosphorylated Tau in exosomes were measured. Then we isolated exosomes from wildtype and Tau-knockout mice after TBI...
February 3, 2018: Molecular and Cellular Neurosciences
Teresa Mammone, Glyn Chidlow, Robert J Casson, John P M Wood
BACKGROUND: Glaucoma is a leading cause of irreversible blindness manifesting as an age-related, progressive optic neuropathy with associated retinal ganglion cell (RGC) loss. Mitogen-activated protein kinases (MAPKs: p42/44 MAPK, SAPK/JNK, p38 MAPK) are activated in various retinal disease models and likely contribute to the mechanisms of RGC death. Although MAPKs play roles in the development of retinal pathology, their action in the optic nerve head (ONH), where the initial insult to RGC axons likely resides in glaucoma, remains unexplored...
February 2, 2018: Molecular and Cellular Neurosciences
Christine M Toedebusch, John C Snyder, Maria R Jones, Virginia B Garcia, Gayle C Johnson, Eric L Villalón, Joan R Coates, Michael L Garcia
Toxicity within superoxide dismutase-1 (SOD1)-associated familial amyotrophic lateral sclerosis (ALS) is non-cell autonomous with direct contribution from microglia. Microglia exhibit variable expression of neuroprotective and neurotoxic molecules throughout disease progression. The mechanisms regulating microglial phenotype within ALS are not well understood. This work presents a first study to examine the specific microglial phenotypic response in close association to motor neurons in a naturally occurring disease model of ALS, canine degenerative myelopathy (DM)...
February 2, 2018: Molecular and Cellular Neurosciences
X Du, K Serena, W Hwang, A M Grech, Y W C Wu, A Schroeder, R A Hill
Brain-derived neurotrophic factor (BDNF) is known to play a critical role early in the development of cortical GABAergic interneurons. Recently our laboratory and others have shown protracted development of specific subpopulations of GABAergic interneurons extending into adolescence. BDNF expression also changes significantly across adolescent development. However the role of BDNF in regulating GABAergic changes across adolescence remains unclear. Here, we performed a week-by-week analysis of the protein expression and cell density of three major GABAergic interneurons, parvalbumin (PV), somatostatin (SST) and calretinin (Cal) in the medial prefrontal cortex from prepubescence (week 3) to adulthood (week 12)...
February 2, 2018: Molecular and Cellular Neurosciences
Chunyu Cao, Yifei Ding, Xiangjun Kong, Guangde Feng, Wei Xiang, Long Chen, Fang Yang, Ke Zhang, Mingxing Chu, Pingqing Wang, Baoyun Zhang
The hypothalamic-pituitary-gonadal (HPG) axis plays a critical role in regulating reproductive function. Gonadotropin-releasing hormone (GnRH), which is secreted by the hypothalamus, acts on pituitary gonadotrophs to stimulate luteinizing hormone (LH) and follicle-stimulating hormone (FSH) synthesis and secretion, ultimately affecting the animal's fertility. MicroRNAs are small, non-coding RNAs that are widely expressed throughout the brain and can fine-tune gene expression post-transcriptionally. Recently, growing evidence has unveiled the central position of miRNAs within a key regulatory process involving GnRH secretion and subsequent activation in the pituitary...
January 30, 2018: Molecular and Cellular Neurosciences
Markella Katidou, Xavier Grosmaitre, Jiangwei Lin, Peter Mombaerts
In the mouse, most mature olfactory sensory neurons (OSNs) express one allele of one gene from the repertoire of ~1100 odorant receptor (OR) genes, which encode G-protein coupled receptors (GPCRs). Axons of OSNs that express a given OR coalesce into homogeneous glomeruli, which reside at conserved positions in the olfactory bulb. ORs are intimately involved in ensuring the expression of one OR per OSN and the coalescence of OSN axons into glomeruli. But the mechanisms whereby ORs accomplish these diverse functions remain poorly understood...
January 30, 2018: Molecular and Cellular Neurosciences
Abeje Ambaw, Lingxing Zheng, Mitali A Tambe, Katherine E Strathearn, Glen Acosta, Scott A Hubers, Fang Liu, Seth A Herr, Jonathan Tang, Alan Truong, Elwood Walls, Amber Pond, Jean-Christophe Rochet, Riyi Shi
Growing evidence suggests that oxidative stress plays a critical role in neuronal destruction characteristic of Parkinson's disease (PD). However, the molecular mechanisms of oxidative stress-mediated dopaminergic cell death are far from clear. In the current investigation, we tested the hypothesis that acrolein, an oxidative stress and lipid peroxidation (LPO) product, is a key factor in the pathogenesis of PD. Using a combination of in vitro, in vivo, and cell free models, coupled with anatomical, functional, and behavioral examination, we found that acrolein was elevated in 6-OHDA-injected rats, and behavioral deficits associated with 6-OHDA could be mitigated by the application of the acrolein scavenger hydralazine, and mimicked by injection of acrolein in healthy rats...
January 29, 2018: Molecular and Cellular Neurosciences
Jimena Hebe Martinez, Agustina Alaimo, Roxana Mayra Gorojod, Soledad Porte Alcon, Federico Fuentes, Federico Coluccio Leskow, Mónica Lidia Kotler
Parkinson's disease is a neurodegenerative movement disorder caused by the loss of dopaminergic neurons from substantia nigra. It is characterized by the accumulation of aggregated α-synuclein as the major component of the Lewy bodies. Additional common features of this disease are the mitochondrial dysfunction and the activation/inhibition of autophagy both events associated to the intracellular accumulation of α-synuclein. The mechanism by which these events contribute to neural degeneration remains unknown...
January 27, 2018: Molecular and Cellular Neurosciences
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