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Molecular and Cellular Neurosciences

Tomoyuki Ueda, Masatoshi Inden, Yuta Asaka, Yuji Masaki, Hisaka Kurita, Wakako Tanaka, Eiji Yamaguchi, Akichika Itoh, Isao Hozumi
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive muscle weakness, paralysis, and death. Although its neuropathology is well investigated, currently, effective treatments are unavailable. The mechanism of ALS involves the aggregation and accumulation of several mutant proteins, including mutant copper‑zinc superoxide dismutase (SOD1), TAR DNA binding protein 43 kDa (TDP-43) and fused in sarcoma (FUS) proteins. Previous reports have shown that excessive oxidative stress, associated with mitochondrial dysfunction and mutant protein accumulation, contributes to ALS pathology...
September 4, 2018: Molecular and Cellular Neurosciences
Qian Zhang, Chengwu Li, Ting Zhang, Yaping Ge, Xiaojuan Han, Sifan Sun, Jianhua Ding, Ming Lu, Gang Hu
ATP-sensitive potassium (K-ATP) channels express in the central nervous system extensively which coupling cell metabolism and cellular electrical activity. K-ATP channels in mature substantia nigra (SN) dopaminergic (DA) neurons are composed of inwardly rectifying potassium channel (Kir) subunit 6.2 and sulfonylurea receptor 1 (SUR1). Our previous study revealed that regulating K-ATP channel exerts the protective effect on DA neurons in a mouse model of Parkinson's disease (PD). However, the detailed mechanism underlying the role of Kir6...
August 29, 2018: Molecular and Cellular Neurosciences
Annie Vu, Tyler Humphries, Sean Vogel, Adam Haberman
Expansions of polygutamine-encoding stretches in several genes cause neurodegenerative disorders including Huntington's Disease and Spinocerebellar Ataxia type 3. Expression of the human disease alleles in Drosophila melanogaster neurons recapitulates cellular features of these disorders, and has therefore been used to model the cell biology of these diseases. Here, we show that polyglutamine disease alleles expressed in Drosophila photoreceptors disrupt actin structure at rhabdomeres, as other groups have shown they do in Drosophila and mammalian dendrites...
August 24, 2018: Molecular and Cellular Neurosciences
Avery J Zucco, Valentina Dal Pozzo, Alina Afinogenova, Ronald P Hart, Orrin Devinsky, Gabriella D'Arcangelo
Tuberous Sclerosis Complex (TSC) is a disease caused by autosomal dominant mutations in the TSC1 or TSC2 genes, and is characterized by tumor susceptibility, brain lesions, seizures and behavioral impairments. The TSC1 and TSC2 genes encode proteins forming a complex (TSC), which is a major regulator and suppressor of mammalian target of rapamycin complex 1 (mTORC1), a signaling complex that promotes cell growth and proliferation. TSC1/2 loss of heterozygosity (LOH) and the subsequent complete loss of TSC regulatory activity in null cells causes mTORC1 dysregulation and TSC-associated brain lesions or other tissue tumors...
August 23, 2018: Molecular and Cellular Neurosciences
Hannes Glaß, Arun Pal, Peter Reinhardt, Jared Sterneckert, Florian Wegner, Alexander Storch, Andreas Hermann
Mutations in the VPS13A gene leading to depletion of chorein protein are causative for Chorea Acanthocytosis (ChAc), a rare devastating disease, which is characterized by neurodegeneration mainly affecting the basal ganglia as well as deformation of erythrocytes. Studies on patient blood samples highlighted a dysregulation of Actin cytoskeleton caused by downregulation of the PI3K pathway and hyper-activation of Lyn-kinase, but to what extent these mechanisms are present and relevant in the affected neurons remains elusive...
August 3, 2018: Molecular and Cellular Neurosciences
Matt C Danzi, Saloni T Mehta, Kireeti Dulla, Giulia Zunino, Daniel J Cooper, John L Bixby, Vance P Lemmon
Axon regeneration is a necessary step toward functional recovery after spinal cord injury. The AP-1 transcription factor c-Jun has long been known to play an important role in directing the transcriptional response of Dorsal Root Ganglion (DRG) neurons to peripheral axotomy that results in successful axon regeneration. Here we performed ChIPseq for Jun in mouse DRG neurons after a sciatic nerve crush or sham surgery in order to measure the changes in Jun's DNA binding in response to peripheral axotomy. We found that the majority of Jun's injury-responsive changes in DNA binding occur at putative enhancer elements, rather than proximal to transcription start sites...
August 3, 2018: Molecular and Cellular Neurosciences
Philippe Ducharme, Juan G Zarruk, Samuel David, Joanne Paquin
Ceruloplasmin (Cp) is an important extracellular regulator of iron metabolism. We showed previously that it stimulates Reelin proteolytic processing and cell aggregation in cultures of developing neurons. Reelin is a secreted protein required for the correct positioning of neurons in the brain. It is cleaved in vivo into N-terminally-derived 300K and 180K fragments through incompletely known mechanisms. One of Reelin signaling targets is the actin-binding protein cofilin, the phosphorylation of which is diminished in Reelin-deficient mice...
August 2, 2018: Molecular and Cellular Neurosciences
Daniel L Egbenya, Suleman Hussain, Yi-Chen Lai, Jun Xia, Anne E Anderson, Svend Davanger
Excitotoxicity caused by excessive stimulation of glutamate receptors, resulting in pathologically increased Ca2+ -concentrations, is a decisive factor in neurodegenerative diseases. We investigated long-term changes in synaptic contents of AMPA receptor subunits that play important roles in calcium regulation in chronic epilepsy. Such plastic changes may be either adaptive or detrimental. We used a kainic acid (KA)-based rat model of chronic temporal lobe epilepsy (TLE). Using hippocampal synaptosomes, we found significant reductions in the concentration of the AMPA receptor subunits GluA1 and GluA2, and the NMDA receptor subunit NR2B...
July 29, 2018: Molecular and Cellular Neurosciences
Blanka R Szulc, Stephen T Hilton, Arnaud J Ruiz
We have synthesized a novel small molecule based on the pyrrolidinone-containing core structure of clausenamide, which is a candidate anti-dementia drug. The synthetic route yielded multi-gram quantities of an isomeric racemate mixture in a short number of steps. When tested in hippocampal slices from young adult rats the compound enhanced AMPA receptor-mediated signalling at mossy fibre synapses, and potentiated inward currents evoked by local application of l-glutamate onto CA3 pyramidal neurons. It facilitated the induction of mossy fibre LTP, but the magnitude of potentiation was smaller than that observed in untreated slices...
July 22, 2018: Molecular and Cellular Neurosciences
Jacqueline E McDermott, Dena Goldblatt, Suzanne Paradis
To understand how proper circuit formation and function is established in the mammalian brain, it is necessary to define the genes and signaling pathways that instruct excitatory and inhibitory synapse development. We previously demonstrated that the ligand-receptor pair, Sema4D and Plexin-B1, regulates inhibitory synapse development on an unprecedentedly fast time-scale while having no effect on excitatory synapse development. Here, we report previously undescribed synaptogenic roles for Sema4A and Plexin-B2 and provide new insight into Sema4D and Plexin-B1 regulation of synapse development in rodent hippocampus...
July 4, 2018: Molecular and Cellular Neurosciences
Tomohiko Maruo, Shotaro Sakakibara, Muneaki Miyata, Yu Itoh, Souichi Kurita, Kenji Mandai, Takuya Sasaki, Yoshimi Takai
A hippocampal mossy fiber synapse has a complex structure in which presynaptic boutons attach to the dendritic trunk by puncta adherentia junctions (PAJs) and wrap multiply-branched spines, forming synaptic junctions. It was previously shown that afadin regulates the formation of the PAJs cooperatively with nectin-1, nectin-3, and N-cadherin. Afadin is a nectin-binding protein with two splice variants, l-afadin and s-afadin: l-afadin has an actin filament-binding domain, whereas s-afadin lacks it. It remains unknown which variant is involved in the formation of the PAJs or how afadin regulates it...
June 30, 2018: Molecular and Cellular Neurosciences
Alina Monteagudo, Julianne Feola, Heather Natola, Changyi Ji, Christoph Pröschel, Gail V W Johnson
Astrocytes play an indispensable role in maintaining a healthy, functional neural network in the central nervous system (CNS). A primary function of CNS astrocytes is to support the survival and function of neurons. In response to injury, astrocytes take on a reactive phenotype, which alters their molecular functions. Reactive astrocytes have been reported to be both beneficial and harmful to the CNS recovery process subsequent to injury. Understanding the molecular processes and regulatory proteins that determine the extent to which an astrocyte hinders or supports neuronal survival is important within the context of CNS repair...
June 30, 2018: Molecular and Cellular Neurosciences
Ying Wang, Xiaomei Bao, Shiyang Wu, Xiya Shen, Fan Zhang, Zhaoting Lv, Qian Wu, Changnan Xie, Huitao Liu, Jian Lin, Honglin Teng, Zhihui Huang
Olfactory ensheathing cells (OECs) migrate from olfactory epithelium towards olfactory bulb (OB), contributing to formation of the presumptive olfactory nerve layer during development. However, it remains unclear that molecular mechanism of regulation of OEC migration in OB. In the present study, we found that OECs highly expressed the receptors of semaphorin 3A (Sema3A) in vitro and in vivo, whereas Sema3A displayed a gradient expression pattern with higher in inner layer of OB and lower in outer layer of OB...
June 27, 2018: Molecular and Cellular Neurosciences
Harold D MacGillavry, Casper C Hoogenraad
No abstract text is available yet for this article.
September 2018: Molecular and Cellular Neurosciences
Nathan T Henderson, Matthew B Dalva
Synapses are specialized cell-cell junctions that underlie the function of neural circuits by mediating communication between neurons. Both the formation and function of synapses require tight coordination of signaling between pre- and post-synaptic neurons. Trans-synaptic organizing molecules are important mediators of such signaling. Here we discuss how the EphB and ephrin-B families of trans-synaptic organizing proteins direct synapse formation during early development and regulate synaptic function and plasticity at mature synapses...
September 2018: Molecular and Cellular Neurosciences
Jelena Borovac, Miquel Bosch, Kenichi Okamoto
Activity-dependent plasticity of synaptic structure and function plays an essential role in neuronal development and in cognitive functions including learning and memory. The formation, maintenance and modulation of dendritic spines are mainly controlled by the dynamics of actin filaments (F-actin) through interaction with various actin-binding proteins (ABPs) and postsynaptic signaling messengers. Induction of long-term potentiation (LTP) triggers a cascade of events involving Ca2+ signaling, intracellular pathways such as cAMP and cGMP, and regulation of ABPs such as CaMKII, Cofilin, Aip1, Arp2/3, α-actinin, Profilin and Drebrin...
September 2018: Molecular and Cellular Neurosciences
Eric Jacobi, Jakob von Engelhardt
Fast excitatory transmission at synapses of the central nervous system is mainly mediated by AMPA receptors (AMPARs). Synaptic AMPAR number and function correlates with synaptic strength. AMPARs are thus key proteins of activity-dependent plasticity in neuronal communication. Up- or down-regulation of synaptic AMPAR number is a tightly controlled dynamic process that involves export of receptors from the endoplasmic reticulum (ER) and Golgi apparatus, exocytosis and endocytosis as well as lateral diffusion of the receptors in the cell membrane...
September 2018: Molecular and Cellular Neurosciences
Nicky Scheefhals, Harold D MacGillavry
Glutamate receptors are the most abundant excitatory neurotransmitter receptors in the brain, responsible for mediating the vast majority of excitatory transmission in neuronal networks. The AMPA- and NMDA-type ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate the fast synaptic responses, while metabotropic glutamate receptors (mGluRs) are coupled to downstream signaling cascades that act on much slower timescales. These functionally distinct receptor sub-types are co-expressed at individual synapses, allowing for the precise temporal modulation of postsynaptic excitability and plasticity...
September 2018: Molecular and Cellular Neurosciences
Marie-Jeanne Papandréou, Christophe Leterrier
The cytoskeleton builds and supports the complex architecture of neurons. It orchestrates the specification, growth, and compartmentation of the axon: axon initial segment, axonal shaft, presynapses. The cytoskeleton must then maintain this intricate architecture for the whole life of its host, but also drive its adaptation to new network demands and changing physiological conditions. Microtubules are readily visible inside axon shafts by electron microscopy, whereas axonal actin study has long been focused on dynamic structures of the axon such as growth cones...
September 2018: Molecular and Cellular Neurosciences
Katharine R Smith, Peter Penzes
Ankyrins are broadly expressed adaptors that organize diverse membrane proteins into specialized domains and link them to the sub-membranous cytoskeleton. In neurons, ankyrins are known to have essential roles in organizing the axon initial segment and nodes of Ranvier. However, recent studies have revealed novel functions for ankyrins at synapses, where they organize and stabilize neurotransmitter receptors, modulate dendritic spine morphology and control adhesion to the presynaptic site. Ankyrin genes have also been highly associated with a range of neurodevelopmental and psychiatric diseases, including bipolar disorder, schizophrenia and autism, which all demonstrate overlap in their genetics, mechanisms and phenotypes...
September 2018: Molecular and Cellular Neurosciences
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