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Journal of Neurochemistry

V H Azocar, G Sepúlveda, C Ruiz, C Aguilera, E Andrés, J A Fuentealba
Kappa opioid receptors (KOR) control dopamine (DA) levels in the striatum and contribute significantly to the progression of drug addiction. Repeated exposure to psychostimulants has been associated with up-regulated KOR activity and increased DA levels in dorsal striatum. However, it has not been tested if both processes are linked. In this work, we studied if a mechanism mediated by KOR is contributing to the increase of DA levels in the dorsolateral striatum (DLS) after amphetamine (AMPH) sensitization. The AMPH sensitization was assessed after single or repeated once-a-day AMPH injections (1mg/kg)...
October 13, 2018: Journal of Neurochemistry
Yogita Kanan, Mahmood Khan, Valeria E Lorenc, Da Long, Rishi Chadha, Jason Sciamanna, Ken Green, Peter A Campochiaro
Metipranolol is a β-adrenergic receptor antagonist that is given orally for the treatment of hypertension and also applied topically to the cornea for treating glaucoma. It also inhibits nitrosative stress which has previously been shown to be the cause of cone photoreceptor death in retinitis pigmentosa (RP). In this study, we tested the hypothesis that metipranolol protects photoreceptor structure and function in the mouse model rd10. At P35, compared with vehicle-treated rd10 mice in which rod degeneration was nearly complete, rd10 mice given daily subcutaneous injections of 40 mg/kg of metipranolol had reduction in markers of nitrosative stress, fewer TUNEL-positive cells, increased outer nuclear layer (ONL) thickness, and substantially more staining for rhodopsin...
October 13, 2018: Journal of Neurochemistry
Rajesh Kushwaha, Juhi Mishra, Anand Prakash Gupta, Keerti Gupta, Jitendra Vishwakarma, Naibedya Chattopadhyay, Jiaur Rahaman Gayen, Mohan Kamthan, Sanghamitra Bandyopadhyay
The anti-diabetic drug and peroxisome proliferator-activated receptor-gamma (PPARγ) agonist, rosiglitazone, alters astrocyte activation; however, its mechanism remains less-known. We hypothesized participation of epidermal growth factor receptor (EGFR), known to control astrocyte reactivity. We first detected that rosiglitazone promoted glial fibrillary acidic protein (GFAP) expression in primary astrocytes as well as the mouse cerebral cortex, associated with increased EGFR activation. Screening for EGFR ligands revealed a rosiglitazone-mediated increase of heparin-binding epidermal growth factor (HB-EGF) in astrocytes, resulting in HB-EGF release into culture medium and mouse cerebrospinal fluid too...
October 12, 2018: Journal of Neurochemistry
Deepti Sharma, Kalpana Kumari Barhwal, Surya Narayan Biswal, Anup Kumar Srivastava, Pushpendar Bhardwaj, Ashish Kumar, Om Prakash Chaurasia, Sunil Kumar Hota
Brain derived neurotrophic factor (BDNF) which is primarily associated with neuronal survivability, differentiation and synaptic plasticity has been reported to mediate neurodegeneration in hypoxia through its p75 Neurotrophin receptors (p75NTR). The molecular events promoting BDNF mediated pro-death signalling in hypoxia however still remains an enigma. The present study attempts towards deciphering the signalling cascades involved in alteration of BDNF isoforms and its cognate receptor subtypes leading to neurodegeneration in hypoxia...
October 11, 2018: Journal of Neurochemistry
Pedro Cisternas, Juan M Zolezzi, Milka Martinez, Viviana I Torres, G William Wong, Nibaldo C Inestrosa
Dysregulated Wnt signaling is linked to major neurodegenerative diseases, including Alzheimer disease (AD). In mouse models of AD, activation of the canonical Wnt signaling pathway improves learning/memory, but the mechanism for this remains unclear. The decline in brain function in AD patients correlates with reduced glucose utilization by neurons. Here, we test whether improvements in glucose metabolism mediate the neuroprotective effects of Wnt in AD mouse model. APPswe/PS1dE9 transgenic mice were used to model AD, Andrographolide or Lithium was used to activate Wnt signaling, and cytochalasin B was used to block glucose uptake...
October 9, 2018: Journal of Neurochemistry
S Fujita, T Hirota, R Sakiyama, M Baba, I Ieiri
Oxaliplatin is widely used as a key drug in the treatment of colorectal cancer. However, its administration is associated with the dose-limiting adverse effect, peripheral neuropathy. Platinum accumulation in the dorsal root ganglion (DRG) is the major mechanism responsible for oxaliplatin-induced neuropathy. Some drug transporters have been identified as platinum complex transporters in kidney or tumor cells, but not yet in DRG. In the present study, we investigated oxaliplatin transporters and their contribution to peripheral neuropathy...
October 8, 2018: Journal of Neurochemistry
Sonya Dave, Lihua Chen, Chunjiang Yu, Melanie Seaton, Christina E Khodr, Lena Al-Harthi, Xiu-Ti Hu
Methamphetamine (Meth) is a potent and commonly-abused psychostimulant. Meth alters neuron and astrocyte activity; yet the underlying mechanism(s) is not fully understood. Here we assessed the impact of acute Meth on human fetal astrocytes (HFAs) using whole-cell patch-clamping. We found that HFAs displayed a large voltage-gated K+ efflux (IK v ) through Kv /Kv -like channels during membrane depolarization, and a smaller K+ influx (Ikir ) via inward-rectifying Kir /Kir -like channels during membrane hyperpolarization...
October 8, 2018: Journal of Neurochemistry
Katarzyna Kuter, Łukasz Olech, Urszula Głowacka, Martyna Paleczna
Glial pathology precedes symptoms of Parkinson's disease (PD) and multiple other neurodegenerative diseases. Prolonged impairment of astrocytic functions could increase the vulnerability of dopaminergic neurons in the substantia nigra (SN), accelerate their degeneration and affect ability to compensate for partial degeneration at the presymptomatic stages of the disease. The aim of this study was to investigate the astrocyte depletion in the SN, its impact on the dopaminergic system functioning and multiple markers of energy metabolism during the early stages of neurodegeneration and compensation...
October 8, 2018: Journal of Neurochemistry
Ka Wan Li, Andrea B Ganz, August B Smit
Dementias are prevalent brain disorders in the aged population. Dementias pose major socio-medical burden, but currently there is no cure available. Novel proteomics approaches hold promise to identify alterations of the brain proteome that could provide clues on disease etiology, and identify candidate proteins to develop further as a biomarker. In this review, we focus on recent proteomics findings from brains affected with Alzheimer's Disease, Parkinson Disease Dementia, Frontotemporal Dementia, and Amyotrophic Lateral Sclerosis...
October 5, 2018: Journal of Neurochemistry
Che-Lin Hu, Mara Nydes, Kara L Shanley, Itzy E Morales Pantoja, Tamara A Howard, Oscar A Bizzozero
Glutathione peroxidase 4 (GPx4) is the only enzyme capable of reducing toxic lipid hydroperoxides in biological membranes to the corresponding alcohols using GSH as the electron donor. GPx4 is the major inhibitor of ferroptosis, a non-apoptotic and iron-dependent programmed cell death pathway, which has been shown to occur in various neurological disorders with severe oxidative stress. In this study, we investigate whether GPx4 expression is altered in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE)...
October 5, 2018: Journal of Neurochemistry
Annelise Francisco, Juliana A Ronchi, Claudia D C Navarro, Tiago R Figueira, Roger F Castilho
Among mitochondrial NADP-reducing enzymes, nicotinamide nucleotide transhydrogenase (NNT) establishes an elevated matrix NADPH/NADP+ by catalyzing the reduction of NADP+ at the expense of NADH oxidation coupled to inward proton translocation across the inner mitochondrial membrane. Here, we characterize NNT activity and mitochondrial redox balance in the brain using a congenic mouse model carrying the mutated Nnt gene from the C57BL/6J strain. The absence of NNT activity resulted in lower total NADPH sources activity in the brain mitochondria of young mice, an effect that was partially compensated in aged mice...
October 3, 2018: Journal of Neurochemistry
Nicole Amberg, Susanne Laukoter, Simon Hippenmeyer
The cerebral cortex is composed of a large variety of distinct cell-types including projection neurons, interneurons and glial cells which emerge from distinct neural stem cell (NSC) lineages. The vast majority of cortical projection neurons and certain classes of glial cells are generated by radial glial progenitor cells (RGPs) in a highly orchestrated manner. Recent studies employing single cell analysis and clonal lineage tracing suggest that NSC and RGP lineage progression are regulated in a profound deterministic manner...
October 1, 2018: Journal of Neurochemistry
Daniele Bottai, Raffaella Adami, Riccardo Ghidoni
Until a few years ago, the majority of cell functions were envisioned as the result of protein and DNA activity. The cell membranes were considered as a mere structure of support and/or separation. In the last years, the function of cell membranes has, however, received more attention and their components of lipid nature have also been depicted as important cell mediators and the membrane organization was described as an important determinant for membrane-anchored proteins activity. In particular, due to their high diversity, glycosphingolipids offer a wide possibility of regulation...
September 30, 2018: Journal of Neurochemistry
Ian F Harrison, Nicholas M Powell, David T Dexter
Histone hypoacetylation is associated with dopaminergic neurodegeneration in Parkinson's disease (PD), due to an imbalance in the activities of the enzymes responsible for histone (de)acetylation. Correction of this imbalance, with histone deacetylase (HDAC) inhibiting agents, could be neuroprotective. We therefore hypothesise that nicotinamide, being a selective inhibitor of HDAC class III as well as having modulatory effects on mitochondrial energy metabolism, would be neuroprotective in the lactacystin rat model of PD, which recapitulates the formation of neurotoxic accumulation of altered proteins within the substantia nigra to cause progressive dopaminergic cell death...
September 30, 2018: Journal of Neurochemistry
Matti Myllykoski, Maria A Eichel, Ramona B Jung, Sørge Kelm, Hauke B Werner, Petri Kursula
The close association of myelinated axons and their myelin sheaths involves numerous intercellular molecular interactions. For example, myelin-associated glycoprotein (MAG) mediates myelin-to-axon adhesion and signalling via molecules on the axonal surface. However, knowledge about intracellular binding partners of myelin proteins, including MAG, has remained limited. The two splice isoforms of MAG, S- and L-MAG, display distinct cytoplasmic domains and spatiotemporal expression profiles. We used yeast 2-hybrid screening to identify interaction partners of L-MAG and found the dynein light chain DYNLL1 (also termed DLC8)...
September 27, 2018: Journal of Neurochemistry
Keietsu Kikuchi, Daisuke Ihara, Mamoru Fukuchi, Hiroki Tanabe, Yuta Ishibashi, Junya Tsujii, Masaaki Tsuda, Marisa Kaneda, Hiroyuki Sakagami, Hiroyuki Okuno, Haruhiko Bito, Yuya Yamazaki, Mitsuru Ishikawa, Akiko Tabuchi
The expression of immediate early genes (IEGs) is thought to be an essential molecular basis of neuronal plasticity for higher brain function. Many IEGs contain serum response element (SRE) in their transcriptional regulatory regions and their expression is controlled by serum response factor (SRF). SRF is known to play a role in concert with transcriptional cofactors. However, little is known about how SRF cofactors regulate IEG expression during the process of neuronal plasticity. We hypothesized that one of the SRF-regulated neuronal IEGs, activity-regulated cytoskeleton-associated protein (Arc; also termed Arg3...
September 23, 2018: Journal of Neurochemistry
J Koppel, H Jimenez, L Adrien, E Chang, A K Malhotra, P Davies
In Alzheimer's disease (AD), the phosphorylation of tau is a critical event preceding the formation of neurofibrillary tangles. Previous work exploring the impact of a dopamine blocking antipsychotic on tau phosphorylation in a tau transgenic model suggested that extracellular dopamine may play a regulatory role in the phosphorylation state of tau. In order to test this hypothesis, and in order to develop a mouse model of impaired dopamine metabolism and tauopathy, an extant P301L transgenic tau model of AD and a novel P301L/catechol-O-methyltransferase deleted model (DM mouse) were treated with the norepinephrine reuptake inhibitor reboxetine, and prefrontal dopamine concentrations and the phosphorylated state of tau was quantified...
September 20, 2018: Journal of Neurochemistry
Ann Brinkmalm, Erik Portelius, Gunnar Brinkmalm, Josef Pannee, Rahil Dahlén, Johan Gobom, Kaj Blennow, Henrik Zetterberg
Neurodegenerative dementias constitute a broad group of diseases in which abnormally folded proteins accumulate in specific brain regions and result in tissue reactions that eventually cause neuronal dysfunction and degeneration. Depending on where in the brain this happens, symptoms appear which may be used to classify the disorders on clinical grounds. However, brain changes in neurodegenerative dementias start to accumulate many years prior to symptom onset and there is a poor correlation between the clinical picture and what pathology that is the most likely to cause it...
September 20, 2018: Journal of Neurochemistry
Omar de Faria, David Gonsalvez, Madeline Nicholson, Junhua Xiao
Myelin, the multilayered membrane surrounding many axons in the nervous system, increases the speed by which electrical signals travel along axons and facilitates neuronal communication between distant regions of the nervous system. However, how neuronal signals influence the myelinating process in the central nervous system (CNS) is still largely unclear. Recent studies have significantly advanced this understanding, identifying important roles for neuronal activity in controlling oligodendrocyte development and their capacity of producing myelin in both developing and mature CNS...
September 17, 2018: Journal of Neurochemistry
Li Zhou, M Ibrahim Hossain, Maya Yamazaki, Manabu Abe, Rie Natsume, Kohtaro Konno, Shun Kageyama, Masaaki Komatsu, Masahiko Watanabe, Kenji Sakimura, Hirohide Takebayashi
Purkinje cell degeneration (pcd) was first identified in a spontaneous mouse mutant showing cerebellar ataxia. In addition to cerebellar Purkinje cells (PCs), retinal photoreceptors, mitral cells in the olfactory bulb, and a discrete subpopulation of thalamic neurons also degenerate in the mutant brains. The gene responsible for the pcd mutant is Nna1, also known as ATP/GTP binding protein 1 or cytosolic carboxypeptidase like 1, which encodes a zinc carboxypeptidase protein. To investigate pathogenesis of the pcd mutation in detail, we generated a conditional Nna1 allele targeting the carboxypeptidase domain at C-terminus...
September 17, 2018: Journal of Neurochemistry
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