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Journal of Neurochemistry

Angelika Więckowska, Olga Gajewska-Woźniak, Anna Głowacka, Benjun Ji, Kamil Grycz, Julita Czarkowska-Bauch, Małgorzata Skup
Complete thoracic spinal cord transection (SCT) impairs excitatory cholinergic inputs to ankle extensor (Soleus; Sol) but not to flexor (Tibialis Anterior; TA) α-motoneurons (MNs) modifiable by locomotor training applied post-transection. The purpose of this study was to investigate whether Sol and TA MNs adapt to changes in cholinergic environment by differential regulation of their muscarinic receptors M2 (M2R). We examined Chrm2 (M2R gene) transcript level, high-affinity [3 H]QNB ligand binding, distribution and density of M2R immunolabeling in lumbar (L) segments in intact and SCT rats, with or without inclusion of 5-week treadmill locomotor training...
August 13, 2018: Journal of Neurochemistry
Cui Liu, Yan Xue, Mei-Fang Liu, Ying Wang, Zi-Ran Liu, Hui-Ling Diao, Lei Chen
Orexin is a member of neuropeptides which is involved in the central motor control. The substantia nigra pars compacta (SNc) is an important nucleus participating in motor control under both physiological and pathological conditions. Morphological studies reveal that orexinergic neurons located in lateral hypothalamus innervate the SNc. Both orexin-1 receptors (OX1 R) and orexin-2 receptors (OX2 R) are expressed in the SNc. To investigate the effects of orexins on SNc, single unit in vivo extracellular recordings and behavioral tests were performed in the present study...
August 13, 2018: Journal of Neurochemistry
Lakshya Bajaj, Parisa Lotfi, Rituraj Pal, Alberto di Ronza, Jaiprakash Sharma, Marco Sardiello
This review focuses on the pathways that regulate lysosome biogenesis and that are implicated in numerous degenerative storage diseases, including lysosomal storage disorders and late-onset neurodegenerative diseases. Lysosomal proteins are synthesized in the endoplasmic reticulum and trafficked to the endolysosomal system through the secretory route. Several receptors have been characterized that execute post-Golgi trafficking of lysosomal proteins. Some of them recognize their cargo proteins based on specific amino acid signatures, others based on a particular glycan modification that is exclusively found on lysosomal proteins...
August 9, 2018: Journal of Neurochemistry
Munal Babu Kandel, Saki Yamamoto, Ryosuke Midorikawa, Jyoji Morise, Yoshihiko Wakazono, Shogo Oka, Kogo Takamiya
The AMPA-type glutamate receptor (AMPA-R) plays a primary role in principal excitatory synaptic transmission and many neuronal functions including synaptic plasticity that underlie learning and memory. N-glycosylation is one of the major post-translational modifications of membrane proteins, but its specific roles in neurons remain largely unknown. AMPA-R subunits are N-glycosylated at their extracellular domains during their biosynthesis in the lumen of the endoplasmic reticulum and Golgi system. Six N-glycosylation sites are presumed to exist in the extracellular domain of GluA1, which is a member of the AMPA-R subunits...
August 9, 2018: Journal of Neurochemistry
Ryan D Mills, Lung-Yu Liang, Daisy Sio-Seng Lio, Yee-Foong Mok, Terrence D Mulhern, George Cao, Michael Griffin, Vijaya Kenche, Janetta G Culvenor, Heung-Chin Cheng
The Parkinson's disease (PD)-causative leucine-rich repeat kinase 2 (LRRK2) belongs to the Roco family of G-proteins comprising a Ras-of-complex (Roc) domain followed by a C-terminal of Roc (COR) domain in tandem (called Roc-COR domain). Two prokaryotic Roc-COR domains have been characterized as "G proteins activated by guanine nucleotide-dependent dimerization" (GADs), which require dimerization for activation of their GTPase activity and bind guanine nucleotides with relatively low affinities. Additionally, LRRK2 Roc domain in isolation binds guanine nucleotides with relatively low affinities...
August 8, 2018: Journal of Neurochemistry
Michael E Cahill, Caleb Browne, Junshi Wang, Peter J Hamilton, Yan Dong, Eric J Nestler
The nucleus accumbens (NAc) is a critical brain reward region that mediates the rewarding effects of drugs of abuse, including those of morphine and other opiates. Drugs of abuse induce widespread alterations in gene transcription and dendritic spine morphology in medium spiny neurons (MSNs) of the NAc that ultimately influence NAc excitability and hence reward-related behavioral responses. Growing evidence indicates that within the NAc small GTPases are common intracellular targets of drugs of abuse where these molecules regulate drug-mediated transcriptional and spine morphogenic effects...
August 2, 2018: Journal of Neurochemistry
Barbara Schweitzer, Jörg B Schulz
The Open Science Framework (OSF) has the mission to increase openness, integrity, and reproducibility in research. The Journal of Neurochemistry became a signatory of their Transparency and Openness guidelines in 2016, which provides eight modular standards (Citation standards, Data Transparency, Analytic Methods/Code Transparency, Research Materials Transparency, Design and Analysis Transparency, Study Pre-registration, Analysis Plan Transparency, Replication) with increasing levels of stringency. Furthermore, OSF recommends and offers a collection of practices intended to make scientific processes and results more transparent and available in a standardized way for reuse to people outside the research team...
August 1, 2018: Journal of Neurochemistry
Ali E Sifat, Bhuvaneshwar Vaidya, Mohammad A Kaisar, Luca Cucullo, Thomas J Abbruscato
Previous studies in our laboratory have shown that nicotine exposure decreases glucose transport across the blood-brain barrier (BBB) in ischemia-reperfusion conditions. We hypothesize that nicotine can also dysregulate brain parenchymal glucose utilization by altering glucose transporters with effects on sensitivity to ischemic stroke. In this study, we investigated the effects of nicotine exposure on neuronal glucose utilization using an in vitro ischemic stroke model. We also tested the effects of e-Cig vaping on ischemic brain glucose utilization using an acute brain slice technique...
July 31, 2018: Journal of Neurochemistry
Young-Hun Jeong, Jung-Hyun Choi, Dohyun Lee, Sangjune Kim, Kyong-Tai Kim
Vaccinia-related kinase 2 (VRK2) is a serine/threonine kinase that belongs to the casein kinase 1 family. VRK2 has long been known for its relationship with to neurodegenerative disorders such as schizophrenia. However, the role of VRK2 and the substrates associated with it are unknown. Dysbindin is known as one of the strong risk factors for schizophrenia. The expression of dysbindin is indeed significantly reduced in schizophrenia patients. Moreover, dysbindin is involved in neurite outgrowth and regulation of N-methyl-D-aspartate receptor (NMDAR) signaling...
July 31, 2018: Journal of Neurochemistry
Simona Scheggi, Maria Graziella De Montis, Carla Gambarana
Dopamine-and cAMP-regulated phosphoprotein (Mr 32 kDa, DARPP-32) is an integrator of multiple neuronal signals and plays a crucial role particularly in mediating the dopaminergic component of the systems involved in the evaluation of stimuli and the ensuing elaboration of complex behavioral responses (e.g., responses to reinforcers and stressors). Dopamine neurons can fire tonically or phasically in distinct timescales and in specific brain regions to code different behaviorally relevant information. Dopamine signaling is mediated mainly through the regulation of adenylyl cyclase activity, stimulated by D1-like or inhibited by D2-like receptors, respectively, that modulates cAMP-dependent protein kinase (PKA) function...
July 25, 2018: Journal of Neurochemistry
Wojciech Michno, Patrick M Wehrli, Kaj Blennow, Henrik Zetterberg, Jörg Hanrieder
Recent advances in the understanding of basic pathological mechanisms in various neurological diseases depend directly on the development of novel bioanalytical technologies that allow sensitive and specific chemical imaging at high resolution in cells and tissues. Mass spectrometry based molecular imaging (IMS) has gained increasing popularity in biomedical research for mapping spatial distribution of molecular species in situ. The technology allows for comprehensive, untargeted delineation of in situ distribution profiles of metabolites, lipids, peptides and proteins...
July 24, 2018: Journal of Neurochemistry
Matthew W Granger, Hui Liu, Caitlin F Fowler, Alexandre P Blanchard, Matthew Taylor, Samantha P M Sherman, Hongbin Xu, Weidong Le, Steffany A L Bennett
Changes in glycerophosphocholine metabolism are observed in Alzheimer's Disease (AD); however, it is not known whether these metabolic disruptions are linked to cognitive decline. Here, using unbiased lipidomic approaches and direct biochemical assessments, we profiled Land's cycle lipid remodelling in the hippocampus, frontal cortex, and temporal-parietal-entorhinal cortices of human amyloid beta precursor protein (ΑβPP) overexpressing mice. We identified a cortex-specific hypo-metabolic signature at symptomatic onset and a cortex-specific hyper-metabolic signature of Land's cycle glycerophosphocholine remodeling over the course of progressive behavioural decline...
July 24, 2018: Journal of Neurochemistry
Erik I Hallin, Maria S Eriksen, Sergei Baryshnikov, Oleksii Nikolaienko, Sverre Grødem, Tomohisa Hosokawa, Yasunori Hayashi, Clive R Bramham, Petri Kursula
The activity-regulated cytoskeleton-associated protein (ARC) is critical for long-term synaptic plasticity and memory formation. Acting as a protein interaction hub, ARC regulates diverse signalling events in postsynaptic neurons. A protein interaction site is present in the ARC C-terminal domain (CTD), a bilobar structure homologous to the retroviral Gag capsid domain. We hypothesized that detailed knowledge of the 3-dimensional molecular structure of monomeric full-length ARC is crucial to understand its function; therefore, we set out to determine the structure of ARC to understand its various functional modalities...
July 20, 2018: Journal of Neurochemistry
Yoshitaka Hayashi, Hideo Jinnou, Kazunobu Sawamoto, Seiji Hitoshi
In the adult mammalian brain, neural stem cells (NSCs) reside in two neurogenic regions, the walls of the lateral ventricles and the subgranular zone of the hippocampus, which generate new neurons for the olfactory bulb and dentate gyrus, respectively. These adult NSCs retain their self-renewal ability and capacity to differentiate into neurons and glia as demonstrated by in vitro studies. However, their contribution to tissue repair in disease and injury is limited, lending credence to the claim by prominent neuropathologist Ramón y Cajal that "once development was ended, the founts of growth and regeneration of the axons and dendrites dried up irrevocably"...
July 20, 2018: Journal of Neurochemistry
Juliana G Doria, Jessica M de Souza, Flavia R Silva, Isabella G Olmo, Toniana G Carvalho, Juliana Alves-Silva, Talita H Ferreira-Vieira, Jessica T Santos, Claudymara Q S Xavier, Nathalia C Silva, Esther M A Maciel, P Jeffrey Conn, Fabiola M Ribeiro
Huntington's Disease (HD) is an autosomal dominant neurodegenerative disorder, characterized by involuntary body movements, cognitive impairment and psychiatric disorder. The metabotropic glutamate receptor 5 (mGluR5) plays an important role in HD and we have recently demonstrated that mGluR5 positive allosteric modulators (PAMs) can ameliorate pathology and the phenotypic signs of a mouse model of HD. In the present study, we investigated the molecular mechanisms involved in mGluR5 PAMs effect on memory. Our results demonstrate that sub-chronic treatment with the mGluR5 PAM VU0409551 was effective in reversing the memory deficits exhibited by BACHD mice, a mouse model for HD...
July 20, 2018: Journal of Neurochemistry
Dustin Chernick, Stephanie Ortiz-Valle, Angela Jeong, Suresh Kumar Swaminathan, Karunya Kandimalla, G William Rebeck, Ling Li
The apolipoprotein (apo) E ε4 allele is the primary genetic risk factor for late-onset Alzheimer's disease (AD). ApoE in the brain is produced primarily by astrocytes; once secreted from these cells, apoE binds lipids and forms high-density lipoprotein (HDL)-like particles. Accumulation of amyloid-β protein (Aβ) in the brain is a key hallmark of AD, and is thought to initiate a pathogenic cascade leading to neurodegeneration and dementia. The level and lipidation state of apoE affect Aβ aggregation and clearance pathways...
July 20, 2018: Journal of Neurochemistry
Stevie van der Mierden, Sergey A Savelyev, Joanna IntHout, Rob B M de Vries, Cathalijn H C Leenaars
Microdialysis is a method to study the extracellular space in vivo, based on the principle of diffusion. It can be used to measure various small molecules including the neuroregulator adenosine. Baseline levels of the compounds measured with microdialysis vary over studies. We systematically reviewed the literature to investigate the full range of reported baseline concentrations of adenosine and AMP in microdialysates. We performed a meta-regression analysis to study the influence of flow rate, probe membrane surface area, species, brain area, and anaesthesia versus freely behaving, on the adenosine concentration...
July 19, 2018: Journal of Neurochemistry
Kazuo Kunisawa, Takeshi Shimizu, Itaru Kushima, Branko Aleksic, Daisuke Mori, Yasuyuki Osanai, Kenta Kobayashi, Anna M Taylor, Manzoor A Bhat, Akiko Hayashi, Hiroko Baba, Norio Ozaki, Kazuhiro Ikenaka
Myelinated axons segregate the axonal membrane into four defined regions: the node of Ranvier, paranode, juxtaparanode and internode. The paranodal junction consists of specific component proteins, such as neurofascin155 (NF155) on the glial side, and Caspr and Contactin on the axonal side. Although paranodal junctions are thought to play crucial roles in rapid saltatory conduction and nodal assembly, the role of their interaction with neurons is not fully understood. In a previous study, conditional NF155 knockout in oligodendrocytes led to disorganization of the paranodal junctions...
July 19, 2018: Journal of Neurochemistry
Anne Sebastiani, Frederik Greve, Christina Gölz, Carola Y Förster, Hermann Koepsell, Serge C Thal
Acute cerebral lesions are associated with dysregulation of brain glucose homeostasis. Previous studies showed that knockdown of Na+ -D-glucose cotransporter SGLT1 impaired outcome after middle cerebral artery occlusion and that widely expressed intracellular RS1 (RSC1A1) is involved in transcriptional and posttranslational downregulation of SGLT1. In the present study, we investigated whether SGLT1 is upregulated during traumatic brain injury (TBI) and whether removal of RS1 in mice (RS1-KO) influences SGLT1 expression and outcome...
July 19, 2018: Journal of Neurochemistry
Stefano Meletti, Chiara Lucchi, Giulia Monti, Giada Giovannini, Roberta Bedin, Tommaso Trenti, Cecilia Rustichelli, Giuseppe Biagini
Neurosteroids such as allopregnanolone may play a role in epilepsy as positive modulators of inhibitory currents mediated by γ-aminobutyric acid type A (GABAA ) receptor. Indeed, these molecules have been consistently shown to be anticonvulsants in animal models, but their role is still unclear in patients. For this reason, we investigated neurosteroids in the cerebrospinal fluid (CSF) of patients with status epilepticus (SE) by liquid chromatography tandem-mass spectrometry. Patients were retrospectively identified within subjects who received a lumbar puncture in the 2007-2017 period...
July 13, 2018: Journal of Neurochemistry
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