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Journal of Neurochemistry

Jean-Martin Beaulieu
Read the highlighted article 'Chronic lithium treatment rectifies maladaptive dopamine release in the nucleus accumbens' on doi/10.1111/jnc.13769.
October 18, 2016: Journal of Neurochemistry
Steven W Barger
Ask any neuroscientist to name the most profound discoveries in the field in the past 60 years, and at or near the top of the list will be a phenomenon or technique related to genes and their expression. Indeed, our understanding of genetics and gene regulation has ushered in whole new systems of knowledge and new empirical approaches, many of which could not have even been imagined prior to the molecular biology boon of recent decades. Neurochemistry, in the classic sense, intersects with these concepts in the manifestation of neuropeptides, obviously dependent upon the central dogma (the established rules by which DNA sequence is eventually converted into protein primary structure) not only for their conformation but also for their levels and locales of expression...
October 17, 2016: Journal of Neurochemistry
Paul Cumming, Jürgen Gallinat
This Editorial highlights a study by Bagga and coworkers (2016) in the current issue of the Journal of Neurochemistry entitled "Mapping the alteration in brain glutamate with glutamate chemical exchange saturation transfer (GluCEST) magnetic resonance imaging in mice with MPTP-induced parkinsonism, a model of dopamine deficiency." Using their spectroscopic procedure, Bagga et al. discern unexpected relative increases in the cortical glutamate content of parkinsonian mice. Their results suggest the occurrence of a simple relationship between striatal astrogliosis and tissue glutamate content, presumably in relation to enhanced glutamate/glutamine cycling...
October 16, 2016: Journal of Neurochemistry
Krisztina Marosi, Sang Woo Kim, Keelin Moehl, Morten Scheibye-Knudsen, Aiwu Cheng, Roy Cutler, Simonetta Camandola, Mark P Mattson
During fasting and vigorous exercise, a shift of brain cell energy substrate utilization from glucose to the ketone 3-hydroxybutyrate (3OHB) occurs. Studies have shown that 3OHB can protect neurons against excitotoxicity and oxidative stress, but the underlying mechanisms are unclear. Neurons maintained in the presence of 3OHB exhibited increased oxygen consumption and ATP production, and an elevated NAD+/NADH ratio. We found that 3OHB metabolism increases mitochondrial respiration which drives changes in expression of brain derived neurotrophic factor (BDNF) in cultured cerebral cortical neurons...
October 14, 2016: Journal of Neurochemistry
A R Jayakumar, X Y Tong, N Shamaladevi, S Barcelona, G Gaidosh, A Agarwal, M D Norenberg
Transactivating DNA-binding protein-43 (TDP-43) inclusions and the accumulation of phosphorylated and ubiquitinated tau proteins (p-tau) have been identified in postmortem brain specimens from patients with chronic traumatic encephalopathy (CTE). To examine whether these proteins contribute to the development of CTE, we utilized an in vitro trauma system known to reproduce many of the findings observed in humans and experimental animals with traumatic brain injury. Accordingly, we examined the role of TDP-43 and Tau in an in vitro model of trauma, and determined whether these proteins contribute to the defective neuronal integrity associated with CNS trauma...
October 13, 2016: Journal of Neurochemistry
Paulo S Pinheiro, Sébastien Houy, Jakob B Sørensen
The molecular mechanisms for calcium-triggered membrane fusion have long been sought for, and detailed models now exist that account for at least some of the functions of the many proteins involved in the process. Key players in the fusion reaction are a group of proteins that, upon binding to calcium, trigger the merger of cargo-filled vesicles with the plasma membrane. Low-affinity, fast-kinetics calcium sensors of the synaptotagmin family - especially synaptotagmin-1 and synaptotagmin-2 - are the main calcium sensors for fast exocytosis triggering in many cell types...
October 12, 2016: Journal of Neurochemistry
Susanne Wegmann, Samantha Nicholls, Shuko Takeda, Zhanyun Fan, Bradley T Hyman
Tau is a neuronal microtubule binding protein that, in Alzheimer's disease and other neurodegenerative diseases, can form oligomeric and large fibrillar aggregates, which deposit in neurofibrillary tangles. Tau's physiological state of multimerization appears to vary across conditions, and a stable dimeric form of soluble tau has been suggested from experiments using recombinant tau in vitro. We tested if tau dimerization, or oligomerization, also occurs in cells, and if soluble tau oligomers are relevant for the release and internalization of tau...
October 12, 2016: Journal of Neurochemistry
Jacob I Ayers, Benjamin McMahon, Sabrina Gill, Herman L Lelie, Susan Fromholt, Hilda Brown, Joan Selverstone Valentine, Julian P Whitelegge, David R Borchelt
A common property of Cu/Zn superoxide dismutase 1 (SOD1), harboring mutations associated with amyotrophic lateral sclerosis (ALS), is a high propensity to misfold and form abnormal aggregates. The aggregation of mutant SOD1 has been demonstrated in vitro, with purified proteins, in mouse models, in human tissues, and in cultured cell models. In vitro translation studies have determined that SOD1 with ALS mutations is slower to mature, and thus perhaps vulnerable to off-pathway folding that could generate aggregates...
October 11, 2016: Journal of Neurochemistry
Sumita Chakrabarti, Andrew Chang, Nai-Jiang Liu, Alan R Gintzler
Caveolin-1 is the predominant structural protein of caveolae, a subset of (lipid) membrane rafts that compartmentalize cell signaling. Caveolin-1 binds most to G protein-coupled receptors and their signaling partners, thereby enhancing interactions among signaling cascade components and the relative activation of specific G protein-coupled pathways. This study reveals that chronic opioid exposure of μ-opioid receptor (MOR) expressing Chinese hamster ovary cells (MOR-CHO) and chronic in vivo morphine exposure of rat spinal cord augmented recruitment of multiple components of MOR-adenylyl cyclase (AC) stimulatory signaling by caveolin-1...
October 10, 2016: Journal of Neurochemistry
Steven F Merkel, Allison M Andrews, Evan M Lutton, Dakai Mu, Eloise Hudry, Bradley T Hyman, Casey A Maguire, Servio H Ramirez
Developing therapies for central nervous system (CNS) diseases is exceedingly difficult due to the blood-brain barrier (BBB). Notably, emerging technologies may provide promising new options for the treatment of CNS disorders. Adeno-associated virus serotype 9 (AAV9) has been shown to transduce cells in the CNS following intravascular administration in rodents, cats, pigs, and non-human primates. These results suggest that AAV9 is capable of crossing the BBB. However, mechanisms that govern AAV9 transendothelial trafficking at the BBB remain unknown...
October 8, 2016: Journal of Neurochemistry
S Cuesta, J Batuecas, M J Severin, A Funes, S B Rosso, A M Pacchioni
Cocaine addiction is a chronic relapsing disorder characterized by the loss of control over drug-seeking and taking, and continued drug use regardless of adverse consequences. Despite years of research, effective treatments for psychostimulant addiction have not been identified. Persistent vulnerability to relapse arises from a number of long lasting adaptations in the reward circuitry that mediate the enduring response to the drug. Recently, we reported that the activity of the canonical or Wnt/β-catenin pathway in the Prefrontal Cortex (PFC) is very important in the early stages of cocaine-induced neuroadaptations...
October 8, 2016: Journal of Neurochemistry
Tao Liu, Hongyu Li, Wanjin Hong, Weiping Han
ADP-ribosylation factor (ARF) family of guanine-nucleotide binding (G) proteins regulates organelle biogenesis, structure and trafficking. The functions of ARF proteins are tightly controlled by guanine nucleotide exchange factors (GEFs) containing a conserved SEC7 domain. Based on sequence similarity to BIG/GBF of the Arf-GEF family, we recently identified brefeldin A-inhibited guanine nucleotide exchange protein 3 (BIG3) as a novel ARF GEF protein with a non-functional catalytic motif in the SEC7 domain. BIG3 is mainly expressed in pancreatic islets and brain...
October 1, 2016: Journal of Neurochemistry
Nicholas V Skladnev, Varshika Ganeshan, Ji Yeon Kim, Thomas Burton, John Mitrofanis, Jonathan Stone, Daniel M Johnstone
Dietary saffron has shown promise as a neuroprotective intervention in clinical trials of retinal degeneration and dementia and in animal models of multiple CNS disorders, including Parkinson's disease. This therapeutic potential makes it important to define the relationship between dose and protection and the mechanisms involved. To explore these two issues, mice were pre-conditioned by providing an aqueous extract of saffron (0.01% w/v) as their drinking water for two, five or ten days before administration of the parkinsonian neurotoxin MPTP (50mg/kg)...
October 1, 2016: Journal of Neurochemistry
Teri M Furlong, Jhodie R Duncan, Laura H Corbit, Caroline D Rae, Benjamin D Rowlands, Anthony D Maher, Fatima A Nasrallah, Carol J Milligan, Steven Petrou, Andrew J Lawrence, Bernard W Balleine
Toluene is a commonly abused inhalant that is easily accessible to adolescents. Despite the increasing incidence of use, our understanding of its long-term impact remains limited. Here we used a range of techniques to examine the acute and chronic effects of toluene exposure on glutameteric and GABAergic function, and on indices of psychological function in adult rats after adolescent exposure. Metabolomics conducted on cortical tissue established that acute exposure to toluene produces alterations in cellular metabolism indicative of a glutamatergic and GABAergic profile...
October 1, 2016: Journal of Neurochemistry
Suliang Chen, Isaac Phang, Argyro Zoumprouli, Marios C Papadopoulos, Samira Saadoun
The management of patients having traumatic spinal cord injury would benefit from understanding and monitoring of spinal cord metabolic states. We hypothesized that the metabolism of the injured spinal cord could be visualized using Kohonen self-organizing maps. Sixteen patients with acute, severe spinal cord injuries were studied. Starting within 72 h of the injury, and for up to a week, we monitored the injury site hourly for tissue glucose, lactate, pyruvate, glutamate, and glycerol using microdialysis as well as intraspinal pressure and spinal cord perfusion pressure...
September 24, 2016: Journal of Neurochemistry
Osamu Imamura, Masaaki Arai, Minori Dateki, Kunio Takishima
Oligodendrocytes are the myelin-forming cells of the central nervous system. Oligodendrocyte loss and failure of myelin development result in serious human disorders, including multiple sclerosis. Previously, using oligodendrocyte progenitor cells, we have shown that donepezil, which is an acetylcholinesterase inhibitor developed for the treatment of Alzheimer's disease, stimulates myelin gene expression and oligodendrocyte differentiation. Here, we aimed to analyze the effects of donepezil on primary mouse embryonic neural stem cells (NSCs)...
September 24, 2016: Journal of Neurochemistry
Maarten Ooms, Bala Attili, Sofie Celen, Michel Koole, Alfons Verbruggen, Koen Van Laere, Guy Bormans
Phosphodiesterase 10A (PDE10A) is a key regulator of medium spiny neuron excitability. Therefore, it plays an important role in the regulation of motor, reward and cognitive processes. Despite the interest in PDE10A as a drug and PET imaging target, little is known about the regulation of PDE10A enzymatic activity. This study aimed to further investigate the role of cAMP in the regulation of PDE10A activity and PDE10A PET imaging. Using [(18) F]JNJ42259152 as radioligand, we investigated alterations in PDE10A binding secondary to changes in cAMP levels...
September 24, 2016: Journal of Neurochemistry
Ying Xu, Ye Tian, Yue Tian, Xingyue Li, Ping Zhao
Hypoxic-ischemic brain injury (HIBI) in neonates can lead to lifelong cognitive and memory impairment, but protective strategies are lacking at present. It has been demonstrated that autophagy plays a critical role in HIBI, while the function of autophagy in cognitive and memory impairment induced by HIBI in neonates has not been tested. In this study, we tested the impact of autophagy on the impairment of cognitive function and memory in HIBI neonatal rats by using a Morris water maze and investigated its possible mechanisms, which were established as HIBI model by ligating the left common carotid artery in neonatal rats, followed by 2-h hypoxia...
September 23, 2016: Journal of Neurochemistry
Alberto Morales-Villagrán, Kenia Pardo-Peña, Laura Medina-Ceja, Silvia López-Pérez
Glutamate measurement in microdialysis samples has primarily been determined using HPLC methods, and several attempts have been made to establish a relationship between this neurotransmitter and EEG activity during altered brain function, such as epilepsy. However, classic microdialysis methods lack high temporal resolution. In this study, a new alternative is proposed to improve the time resolution and thus obtain a better understanding of the dynamics of Glu and its relationship with epileptiform activity...
September 21, 2016: Journal of Neurochemistry
Enrique Calvo-Gallardo, Ángela López-Gil, Iago Méndez-López, Carmen Martínez-Ramírez, J Fernando Padín, Antonio G García
Adrenal chromaffin cells (CCs) have been used extensively in studies aimed at revealing the intricacies of the Ca(2+) -dependent early and late steps of regulated exocytosis. They have also served as invaluable models to study the kinetics of single-vesicle exocytotic events to infer the characteristics of opening and closing of the exocytotic fusion pore. We have here tested the hypothesis that stimulation at room temperature of CCs from mice C57BL/6 with physiological acetylcholine (ACh) and with other secretagogues (DMPP, high K(+) , muscarine, histamine, caffeine), alone or in combination, could trigger amperometric spike events with different kinetics...
September 21, 2016: Journal of Neurochemistry
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