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Journal of Neurochemistry

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https://www.readbyqxmd.com/read/28099989/effects-of-a-dietary-ketone-ester-on-hippocampal-glycolytic-and-tca-cycle-intermediates-and-amino-acids-in-a-3xtgad-mouse-model-of-alzheimer-s-disease
#1
Robert J Pawlosky, Martin F Kemper, Yoshihero Kashiwaya, M Todd King, Mark P Mattson, Richard L Veech
In patients with Alzheimer's disease (AD) and in a triple transgenic (3xTgAD) mouse model of AD low glucose metabolism in the brain precedes loss of memory and cognitive decline. The metabolism of ketones in the brain by-passes glycolysis and therefore may correct several deficiencies that are associated with glucose hypometabolism. A dietary supplement composed of an ester of D-β-hydroxybutyrate and R-1,3 butane diol referred to as ketone ester (KE) was incorporated into a rodent diet and fed to 3xTgAD mice for 8 months...
January 18, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28095639/early-involvement-of-lysosome-dysfunction-in-the-degeneration-of-cerebral-cortical-neurons-caused-by-the-lipid-peroxidation-product-4-hydroxynonenal
#2
Shi Zhang, Erez Eitan, Mark P Mattson
Free radical-mediated oxidative damage to proteins, lipids and DNA occurs in neurons during acute brain injuries and in neurodegenerative disorders. Membrane lipid peroxidation contributes to neuronal dysfunction and death, in part by disrupting neuronal ion homeostasis and cellular bioenergetics. Emerging findings suggest that 4-hydroxynonenal (HNE), an aldehyde produced during lipid peroxidation, impairs the function of various proteins involved in neuronal homeostasis. Here we tested the hypothesis that HNE impairs the cellular system that removes damaged proteins and organelles, the autophagy - lysosome pathway in rat primary cortical neurons...
January 17, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28092095/noradrenergic-transmission-in-the-central-medial-thalamic-nucleus-modulates-the-electroencephalographic-activity-and-emergence-from-propofol-anesthesia-in-rats
#3
Bao Fu, Tian Yu, Jie Yuan, Xingrui Gong, Mazhong Zhang
At present, the mechanisms by which general anesthetics causing loss of consciousness remain unclear. The central medial thalamic nucleus (CMT) is a rarely studied component of the midline thalamic complex, which is deemed to be a part of the nonspecific arousal system. Despite the fact that CMT participates in modulating arousal and receives excitatory noradrenergic projections from locus coeruleus (LC), it remains unknown whether the noradrenergic pathway in the CMT takes part in modulating the arousal system...
January 16, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28075498/tamoxifen-and-its-active-metabolites-inhibit-dopamine-transporter-function-independently-of-the-estrogen-receptors
#4
Sarah R Mikelman, Bipasha Guptaroy, Margaret Gnegy
As one of the primary mechanisms by which dopamine signaling is regulated, the dopamine transporter (DAT) is an attractive pharmacological target for the treatment of diseases based in dopaminergic dysfunction. In this work we demonstrate for the first time that the commonly prescribed breast cancer therapeutic tamoxifen and its major metabolites, 4-hydroxytamoxifen and endoxifen, inhibit DAT function. Tamoxifen inhibits [(3) H]dopamine uptake into hDAT-N2A cells via an uncompetitive or mixed mechanism. Endoxifen, an active metabolite of tamoxifen, asymmetrically inhibits DAT function in hDAT-N2A cells, showing a preference for the inhibition of amphetamine-stimulated dopamine efflux as compared to dopamine uptake...
January 11, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28074610/an-in%C3%A2-vitro-model-yields-importin-new-insights-into-chronic-traumatic-encephalopathy-damaged-astrocytes-stop-thrombospondin-to-the-injury-an-editorial-highlight-for-defective-synthesis-and-release-of-astrocytic-thrombospondin-1-mediates-the-neuronal-tdp-43
#5
EDITORIAL
Sausan M Jaber, Brian M Polster
Read the highlighted article 'Defective synthesis and release of astrocytic thrombospondin-1 mediates the neuronal TDP-43 proteinopathy, resulting in defects in neuronal integrity associated with chronic traumatic encephalopathy: in vitro studies' on doi: 10.1111/jnc.13867.
January 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28072466/chronic-pain-and-impaired-glial-glutamate-transporter-function-in-lupus-prone-mice-are-ameliorated-by-blocking-csf-1-receptors
#6
Xisheng Yan, Dylan W Maixner, Fen Li, Han-Rong Weng
Systemic lupus erythematosus (SLE) is a multi-organ disease of unknown etiology in which the normal immune responses are directed against the body's own healthy tissues. Patients with SLE often suffer from chronic pain. Currently, no animal studies have been reported about the mechanisms underlying pain in SLE. In this study, the development of chronic pain in MRL lupus-prone (MRL/lpr) mice, a well-established lupus mouse model, was characterized for the first time. We found that female MRL/lpr mice developed thermal hyperalgesia at the age of 13 weeks, and mechanical allodynia at the age of 16 weeks...
January 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28072465/splicing-regulation-and-dysregulation-of-cholinergic-genes-expressed-at-the-neuromuscular-junction
#7
REVIEW
Kinji Ohno, Mohammad Alinoor Rahman, Mohammad Nazim, Farhana Nasrin, Yingni Lin, Jun-Ichi Takeda, Akio Masuda
We humans have evolved by acquiring diversity of alternative RNA metabolisms including alternative means of splicing and transcribing non-coding genes, and not by acquiring new coding genes. Tissue-specific and developmental stage-specific alternative RNA splicing is achieved by tightly regulated spatiotemporal regulation of expressions and activations of RNA-binding proteins that recognize their cognate splicing cis-elements on nascent RNA transcripts. Genes expressed at the neuromuscular junction (NMJ) are also alternatively spliced...
January 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28072455/src-and-phospho-fak-kinases-are-activated-by-allopregnanolone-promoting-schwann-cells-motility-morphology-and-myelination
#8
Simona Melfi, Maria Magdalena Montt Guevara, Veronica Bonalume, Massimiliano Ruscica, Alessandra Colciago, Tommaso Simoncini, Valerio Magnaghi
Schwann cells' (SCs) development and maturation require coordinate and complementary interaction among several signals and intracellular pathways. Among factors controlling these processes, the signalling intermediates Src tyrosine kinase and focal adhesion kinase (FAK) are relevant for SCs' fate, participating in regulation of SC adhesion, motility and migration. Recently, the progesterone metabolite allopregnanolone (ALLO) was proved to be synthesized by SCs, whereas it acts autocrinally on SC motility and proliferation, which are crucial processes for nerve development, maturation and regeneration...
January 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28072454/non-neuronal-acetylcholine-involved-in-reproduction-in-mammals-and-honeybees
#9
REVIEW
Ignaz Wessler, Charles James Kirkpatrick
Bacteria and archaea synthesize acetylcholine (ACh). Thus it can be postulated that ACh was created by nature roughly 3 billion years ago. Therefore, the wide expression of ACh in nature (i.e. in bacteria, archaea, unicellular organisms, plants, fungi, non-vertebrates and vertebrates and the abundance of non-neuronal cells of mammals) is not surprising. The term non-neuronal ACh and non-neuronal cholinergic system have been introduced to describe the auto- and paracrine, i.e. local regulatory actions of cells not innervated by neuronal cholinergic fibers to communicate among themselves...
January 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28072448/identification-of-altered-brain-metabolites-associated-with-tnap-activity-in-a-mouse-model-of-hypophosphatasia-using-untargeted-nmr-based-metabolomics-analysis
#10
Thomas Cruz, Marie Gleizes, Stéphane Balayssac, Etienne Mornet, Grégory Marsal, José Luis Millán, Myriam Malet-Martino, Lionel G Nowak, Véronique Gilard, Caroline Fonta
Tissue Nonspecific Alkaline Phosphatase (TNAP) is a key player of bone mineralization and TNAP gene (ALPL) mutations in human are responsible for hypophosphatasia (HPP), a rare heritable disease affecting the mineralization of bones and teeth. Moreover, TNAP is also expressed by brain cells and the severe forms of HPP are associated with neurological disorders, including epilepsy and brain morphological anomalies. However TNAP's role in the nervous system remains poorly understood. In order to investigate its neuronal functions, we aimed to identify without any a priori the metabolites regulated by TNAP in the nervous tissue...
January 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28058727/exppning-how-acetylcholine-improves-gait-in-parkinson-s-disease-an-editorial-highlight-for-deletion-of-the-vesicular-acetylcholine-transporter-from-pedunculopontine-laterodorsal-tegmental-neurons-modifies-gait
#11
EDITORIAL
Björn Falkenburger
Gait impairment is one of the most intractable symptoms of Parkinson's disease, responding poorly to dopaminergic medication. Promising therapeutic strategies include deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) and enhancing cholinergic neurotransmission by acetylcholine esterase inhibitors. This Editorial discusses an elegant study by Janickova and coworkers in the current issue of the Journal of Neurochemistry, in which the authors engineered mice lacking cholinergic transmission selectively in the PPN and demonstrate that cholinergic neurons of the PPN are critical for gait...
January 6, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28054357/linking-amyotrophic-lateral-sclerosis-and-spinal-muscular-atrophy-through-rna-transcriptome-homeostasis-a-genomics-perspective
#12
REVIEW
Margarida Gama-Carvalho, Marina L Garcia-Vaquero, Francisco R Pinto, Florence Besse, Joachim Weis, Aaron Voigt, Jörg B Schulz, Javier De Las Rivas
In this review we present our most recent understanding of key biomolecular processes that underlie two motor neuron degenerative disorders, Amyotrophic Lateral Sclerosis (ALS) and Spinal Muscular Atrophy (SMA). We focus on the role of four multifunctional proteins involved in RNA metabolism (TDP-43, FUS, SMN and Senataxin) that play a causal role in these diseases. Recent results have led to a novel scenario of intricate connections between these four proteins, bringing transcriptome homeostasis into the spotlight as a common theme in motor neuron degeneration...
January 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28054340/fingolimod-confers-neuroprotection-through-activation-of-rac1-after-experimental-germinal-matrix-hemorrhage-in-rat-pups
#13
William B Rolland, Paul R Krafft, Tim Lekic, Damon Klebe, Julia LeGrand, Abby Jones Weldon, Liang Xu, John H Zhang
Fingolimod, a sphingosine-1-phosphate receptor (S1PR) agonist, is clinically available to treat multiple sclerosis and is showing promise in treating stroke. We investigated if fingolimod provides long-term protection from experimental neonatal germinal matrix hemorrhage (GMH), aiming to support a potential mechanism of acute fingolimod-induced protection. GMH was induced in P7 rats by infusion of collagenase (0.3 U) into the right ganglionic eminence. Animals euthanized at four weeks post-GMH received low or high dose fingolimod (0...
January 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28035674/the-blood-brain-barrier-fatty-acid-transport-protein-1-fatp1-slc27a1-supplies-docosahexaenoic-acid-to-the-brain-and-insulin-facilitates-transport
#14
Yusuke Ochiai, Yasuo Uchida, Sumio Ohtsuki, Masanori Tachikawa, Sanshiro Aizawa, Tetsuya Terasaki
We purposed to clarify the contribution of fatty acid transport protein 1 (FATP1/SLC27A1) to the supply of docosahexaenoic acid (DHA) to the brain across the blood-brain barrier in this study. Transport experiments showed that the uptake rate of [(14) C]-DHA in human FATP1-expressing HEK293 cells was significantly greater than that in empty vector-transfected (mock) HEK293 cells. The steady-state intracellular DHA concentration was nearly 2-fold smaller in FATP1-expressing than in mock cells, suggesting that FATP1 works as not only an influx, but also an efflux transporter for DHA...
December 30, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28032911/alanine-substitutions-in-the-gxxxg-motif-alter-c99-cleavage-by-%C3%AE-secretase-but-not-its-dimerization
#15
Hidekazu Higashide, Seiko Ishihara, Mika Nobuhara, Yasuo Ihara, Satoru Funamoto
The amyloid β (Aβ) protein is a major component of senile plaques, one of the neuropathological hallmarks of Alzheimer's disease (AD). Amyloidogenic processing of amyloid precursor protein (APP) by β- and γ-secretases leads to production of Aβ. APP contains tandem triple repeats of the GXXXG motif in its extracellular juxtamembrane and transmembrane regions. It is reported that the GXXXG motif is related to protein-protein interactions, but it remains controversial whether the GXXXG motif in APP is involved in substrate dimerization and whether dimerization affects γ-secretase-dependent cleavage...
December 29, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28029694/type-i-interferons-mediate-the-neuroinflammatory-response-and-neurotoxicity-induced-by-rotenone
#16
Bevan S Main, Moses Zhang, Kate M Brody, Francis J Kirby, Peter J Crack, Juliet M Taylor
Evidence from post-mortem human brains, animal studies and cell culture models has implicated neuroinflammation in the aetiology of chronic neuropathologies including Alzheimer's and Parkinson's diseases. Although the neuroinflammatory response is considered detrimental in contributing to these pathologies, the underlying mechanisms are still not well understood. The type-I interferons (IFNs) have been well characterised in the periphery and are known to initiate/modulate the immune response. Recently, they have been implicated in aging and we have also demonstrated increased type-I IFN expression in post-mortem human Alzheimer's and Parkinson's disease brains...
December 28, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28029679/usp14-inhibitor-attenuates-cerebral-ischemia-reperfusion-induced-neuronal-injury-in-mice
#17
Jia-Wei Min, Lanhai Lü, Jessica Freeling, Doug Martin, Hongmin Wang
Stroke is associated with over-production of misfolded and aggregating proteins. However, it remains largely unclear whether enhanced removal of protein aggregates following ischemic stroke is neuroprotective. Deubiquitinating enzymes (DUBs) are a large group of proteases that regulate protein degradation. The ubiquitin-specific protease 14 (USP14) is a DUB that is associated with the proteasome and negatively regulates proteasome activity. In this study, we examined the effect of IU1, a specific small molecule inhibitor of USP14, on mouse focal cerebral ischemic stroke-induced neuronal injury in mice...
December 28, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28027414/roles-of-p62-in-bdnf-dependent-autophagy-suppression-and-neuroprotection-against-mitochondrial-dysfunction-in-rat-cortical-neurons
#18
Chia-Lin Wu, Chien-Hui Chen, Chi-Shin Hwang, Shang-Der Chen, Wei-Chao Hwang, Ding-I Yang
Previously we have reported that preconditioning of primary rat cortical neurons with brain-derived neurotrophic factor (BDNF) may exert neuroprotective effects against 3-nitropropionic acid (3-NP), a mitochondrial complex II inhibitor. However, the underlying mechanisms, especially potential involvements of autophagy, remain elusive. In this work, we tested the hypothesis that BDNF may suppress 3-NP-induced autophagy to exert its neuroprotective effects by inducing the expression of p62/sequestosome-1 in primary cortical neurons...
December 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28027400/elevated-intracellular-na-concentrations-in-developing-spinal-neurons
#19
Casie Lindsly, Carlos Gonzalez-Islas, Peter Wenner
Over 25 years ago it was first reported that intracellular chloride levels (Cl(-)in ) were higher in developing neurons than in maturity. This finding has had significant implications for understanding the excitability of developing networks and recognizing the underlying causes of hyperexcitability associated with disease and neural injury. While there is some evidence that intracellular sodium levels (Na(+)in ) change during the development of non-neural cells, it has largely been assumed that Na(+)in is the same in developing and mature neurons...
December 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28027399/activation-of-bdnf-trkb-signaling-in-the-pedunculopontine-tegmental-nucleus-ppt-a-novel-mechanism-for-the-homeostatic-regulation-of-rem-sleep
#20
Abigail K Barnes, Richa Koul-Tiwari, Jennifer M Garner, Phillip A Geist, Subimal Datta
REM sleep dysregulation is a symptom of many neuropsychiatric disorders, yet the mechanisms of REM sleep homeostatic regulation are not fully understood. We have shown that, after REM sleep deprivation, the pedunculopontine tegmental nucleus (PPT) plays a critical role in the generation of recovery REM sleep. In the present study, we used multidisciplinary techniques to show a causal relationship between BDNF-TrkB signaling in the PPT and the development of REM sleep homeostatic drive. Rats were randomly assigned to conditions of unrestricted sleep or selective REM sleep deprivation (RSD) with PPT microinjections of vehicle control or a dose of a TrkB receptor inhibitor (2, 3, or 4 nmol K252a or 4 nmol ANA-12)...
December 27, 2016: Journal of Neurochemistry
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