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Journal of Neurochemistry

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https://www.readbyqxmd.com/read/27926996/small-molecule-modulator-of-sigma-2-receptor-is-neuroprotective-and-reduces-cognitive-deficits-and-neuro-inflammation-in-experimental-models-of-alzheimer-s-disease
#1
Bitna Yi, James J Sahn, Pooneh Memar Ardestani, Andrew K Evans, Luisa Scott, Jessica Z Chan, Sangeetha Iyer, Ashley Crisp, Gabriella Zuniga, Jonathan Pierce-Shimomura, Stephen F Martin, Mehrdad Shamloo
Accumulating evidence suggests that modulating the sigma 2 receptor (Sig2R) can provide beneficial effects for neurodegenerative diseases. Herein, we report the identification of a novel class of Sig2R binding ligands and their cellular and in vivo activity in experimental models of Alzheimer's disease (AD). We report that SAS-0132 and DKR-1051, selective ligands of Sig2R, modulate intracellular Ca(2+) levels in human SK-N-SH neuroblastoma cells. The Sig2R antagonists SAS-0132 and JVW-1009 are neuroprotective in a C...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27926984/involvement-of-chemokine-cxcl11-in-the-development-of-morphine-tolerance-in-rats-with-cancer-induced-bone-pain
#2
Genhua Guo, Yawen Peng, Bingrui Xiong, Daiqiang Liu, Huilian Bu, Xuebi Tian, Hui Yang, Zhen Wu, Fei Cao, Feng Gao
Morphine is viewed as one of the classical treatments for intractable pain, but its role is limited by side effects, including analgesic tolerance. A few chemokines have been reported to be engaged in the mechanisms of morphine tolerance. However, the exact roles of CXCL11 in chronic morphine tolerance remain unknown. In this study, Walker 256 mammary gland carcinoma cells were inoculated into the tibia of rats to provoke cancer-induced bone pain (CIBP). Then morphine was intrathecally administered twice daily for 7 consecutive days to induce drug tolerance...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27926982/trpv4-channels-mediate-na-k-cl-co-transporter-induced-brain-edema-after-traumatic-brain-injury
#3
Kwok-Tung Lu, Tai-Chun Huang, Ya-Hsin Tsai, Yi-Ling Yang
Na(+) -K(+) -2Cl(-) co-transporter (NKCC1) plays an important role in traumatic brain injury (TBI)-induced brain edema via the mitogen-activated protein kinases (MAPK) cascade. The transient receptor potential vanilloid type 4 (TRPV4) channel participates in neurogenic inflammation, pain transmission and edema. In this study, we investigated the relationship between NKCC1 and TRPV4 and the related signaling pathways in TBI-induced brain edema and neuronal damage. TBI was induced by the calibrated weight-drop device...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27926980/role-and-regulation-of-p27-in-neuronal-apoptosis
#4
Surbhi Jaiswal, Pushkar Sharma
It is necessary for the cell cycle machinery of neurons to be suppressed to promote differentiation and maintenance of their terminally differentiated state. Reactivation of the cell cycle in response to neurotoxic insults leads to neuronal cell death and some cell cycle related proteins contribute to the process. p27 kip1 (p27), an inhibitor of Cyclin Dependent Kinases (CDKs), prevents unwarranted CDK activation. In the present study, we have elucidated a novel mechanism via which p27 promotes apoptosis of neurons stimulated by neurotoxic amyloid peptide Aβ42 (Amyloid β1-42 peptide)...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27925207/acetate-metabolism-does-not-reflect-astrocytic-activity-contributes-directly-to-gaba-synthesis-and-is-increased-by-silent-information-regulator-1-activation
#5
Benjamin D Rowlands, Matthias Klugmann, Caroline D Rae
[(13) C]acetate is known to label metabolites preferentially in astrocytes rather than neurons and it has consequently been used as a marker for astrocytic activity. Recent discoveries suggest that control of acetate metabolism and its contributions to the synthesis of metabolites in brain is not as simple as first thought. Here, using a Guinea pig brain cortical tissue slice model metabolizing [1-(13) C]D-glucose and [1,2-(13) C]acetate, we investigated control of acetate metabolism and the degree to which it reflects astrocytic activity...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27925201/vascular-inter-regulation-of-inflammation-molecular-and-cellular-targets-for-cns-therapy
#6
REVIEW
Marta Machado-Pereira, Tiago Santos, Liliana Bernardino, Raquel Ferreira
Angiogenesis and inflammation are clearly interconnected and interdependent processes that are dysregulated in a series of systemic and brain pathologies. Herein, key aspects regarding endothelial cell function and tissue remodelling that are particularly affected or aggravated by inflammation are presented. Most importantly, the cellular and molecular mechanisms involved in the vascular regulation of the inflammatory processes occurring in several brain disorders and how they impact on disease/injury progression are detailed, highlighting potential targets for therapy...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27925199/dopamine-dependent-effects-on-basal-and-glutamate-stimulated-network-dynamics-in-cultured-hippocampal-neurons
#7
Yan Li, Xin Chen, Rhonda Dzakpasu, Katherine Conant
Oscillatory activity occurs in cortical and hippocampal networks with specific frequency ranges thought to be critical to working memory, attention, differentiation of neuronal precursors, and memory trace replay. Synchronized activity within relatively large neuronal populations is influenced by firing and bursting frequency within individual cells, and the latter is modulated by changes in intrinsic membrane excitability and synaptic transmission. Published work suggests that dopamine (DA), a potent modulator of learning and memory, acts on dopamine receptor 1-like dopamine receptors (D1Rs) to influence the phosphorylation and trafficking of glutamate receptor subunits, along with long-term potentiation (LTP) of excitatory synaptic transmission in striatum and prefrontal cortex...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27891578/dual-specificity-phosphatase-15-regulates-erk-activation-in-schwann-cells
#8
José F Rodríguez-Molina, Camila Lopez-Anido, Ki H Ma, Chongyu Zhang, Tyler Olson, Katharina N Muth, Matthias Weider, John Svaren
Schwann cells and oligodendrocytes are the myelinating cells of the peripheral and central nervous system, respectively. Despite having different myelin components and different transcription factors driving their terminal differentiation there are shared molecular mechanisms between the two. Sox10 is one common transcription factor required for several steps in development of myelinating glia. However, other factors are divergent as Schwann cells need the transcription factor Egr2/Krox20 and oligodendrocytes require Myrf...
November 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27889927/sp2-is-the-only-glutamine-rich-specificity-protein-with-minor-impact-on-development-and-differentiation-in-myelinating-glia
#9
Amélie Wegener, Melanie Küspert, Elisabeth Sock, Sjaak Philipsen, Guntram Suske, Michael Wegner
Oligodendrocytes and Schwann cells are the myelinating glia of the vertebrate nervous system and by generation of myelin sheaths allow rapid saltatory conduction. Previous in vitro work had pointed to a role of the C2H2 zinc finger Specificity proteins Sp1 and Sp3 as major regulators of glial differentiation and myelination. Here, we asked whether such a role is also evident in vivo using mice with specific deletions of Sp1 or Sp3 in myelinating glia. We also studied glia-specific conditional Sp2- and constitutive Sp4-deficient mice to include all related glutamine-rich Sp factors into our analysis...
November 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27889925/deletion-of-the-vesicular-acetylcholine-transporter-from-pedunculopontine-laterodorsal-tegmental-neurons-modifies-gait
#10
Helena Janickova, Kaie Rosborough, Mohammed Al-Onaizi, Ornela Kljakic, Monica S Guzman, Robert Gros, Marco A M Prado, Vania F Prado
Postural instability and gait disturbances, common disabilities in the elderly and frequently present in Parkinson's disease (PD), have been suggested to be related to dysfunctional cholinergic signalling in the brainstem. We investigated how long-term loss of cholinergic signalling from mesopontine nuclei influence motor behaviours. We selectively eliminated the vesicular acetylcholine transporter (VAChT) in pedunculopontine and laterodorsal tegmental nuclei cholinergic neurons to generate mice with selective mesopontine cholinergic deficiency (VAChT(E)(n1-Cre-flox/flox) )...
November 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27889917/the-neuronal-insulin-receptor-in-its-environment
#11
REVIEW
Matthias Gralle
Insulin is known mainly for its effects in peripheral tissues, such as liver, skeletal muscles and adipose tissue, where the activation of the insulin receptor (IR) has both short-term and long-term effects. Insulin and the IR are also present in the brain, and since there is evidence that neuronal insulin signaling regulates synaptic plasticity and that it is impaired in disease, this pathway might be key to protection or reversal of symptoms, especially in Alzheimer's disease. However, there are controversies about the importance of neuronal IR, partly because biophysical data on its activation and signaling are much less complete than for peripheral IR...
November 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27889915/constitutive-regulation-of-the-glutamate-aspartate-transporter-eaat1-by-calcium-calmodulin-dependent-protein-kinase-ii
#12
Aarti R Chawla, Derrick E Johnson, Agnes S Zybura, Benjamin P Leeds, Ross M Nelson, Andy Hudmon
Glutamate clearance by astrocytes is an essential part of normal excitatory neurotransmission. Failure to adapt or maintain low levels of glutamate in the central nervous system is associated with multiple acute and chronic neurodegenerative diseases. The primary excitatory amino acid transporters in human astrocytes are EAAT1 and EAAT2 (GLAST and GLT-1 respectively in rodents). While the inhibition of calcium/calmodulin-dependent kinase (CaMKII), a ubiquitously-expressed serine/threonine protein kinase, results in diminished glutamate uptake in cultured primary rodent astrocytes (Ashpole et al...
November 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27889911/multiregional-analysis-of-global-5-methylcytosine-and-5-hydroxymethylcytosine-throughout-the-progression-of-alzheimer-s-disease
#13
Elizabeth M Ellison, Erin L Abner, Mark A Lovell
Epigenetic modifications to cytosine are known to alter transcriptional states and deregulate gene expression in cancer, embryonic development, and most recently in neurodegeneration. To test the hypothesis that global levels of cytosine modification are altered throughout the progression of Alzheimer's disease, 5-methylcytosine (5-mC) and 5-hydroxmethylcytosine (5-hmC) were quantified using gas chromatography/mass spectrometry (GC/MS) and stable labeled internal standards of cytosine, 5-mC, and 5-hmC. Cytosine modifications were quantified in DNA extracted from tissue specimens of four brain regions (cerebellum, inferior parietal lobe, superior and middle temporal gyrus, and hippocampus/parahippocampal gyrus) of cognitively normal control (NC) subjects and subjects with mild cognitive impairment (MCI), preclinical Alzheimer's disease (PCAD), late onset Alzheimer's disease (LOAD), frontotemporal lobar degeneration (FTLD) and dementia with Lewy bodies (DLB)...
November 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27889907/activation-of-nur77-in-microglia-attenuates-proinflammatory-mediators-production-and-protects-dopaminergic-neurons-from-inflammation-induced-cell-death
#14
Tian-Ya Liu, Xiao-Ying Yang, Long-Tai Zheng, Guang-Hui Wang, Xue-Chu Zhen
Microglia-mediated neuroinflammation plays a critical role in the pathological development of Parkinson's disease (PD). Orphan nuclear receptor Nur77 (Nur77) is abundant in neurons, while its role in microglia-mediated neuroinflammation remains unclear. The present data demonstrated that the expression of Nur77 in microglia was reduced accompanied with microglia activation in response to lipopolysaccharide (LPS) in vitro and in experimental MPTP-PD mouse model. Nur77 overexpression or application of Nur77 agonist CsnB suppressed the expression of proinflammatory genes, such as iNOS, COX-2, IL-1β, and TNF-α in the activated microglia, while silenced Nur77 exaggerated the inflammatory responses in microglia...
November 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27874976/etidronate-rescues-cognitive-deficits-through-improving-synaptic-transmission-and-suppressing-apoptosis-in-2-vessel-occlusion-model-rats
#15
Wen Li, Huijuan Yuan, Yao Yu, Yuen-Ki Cheong, Guogang Ren, Zhuo Yang
Vascular dementia (VD) is a neurodegenerative disorder caused by the reduction of cerebral blood flow. It shows a progressive cognitive impairment. In our previous study, we found that etidronate (ET) showed neuroprotective effects against glutamate-injured PC12 cells. Thus in this study, we aimed to observe the effects of ET on learning and memory impairment and the related mechanism in 2-vessel occlusion (2VO) model rats. Rats were administered a permanent bilateral common carotid artery occlusion to induce VD model...
November 22, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27874975/structural-and-functional-brain-alterations-in-a-murine-model-of-angiotensin-ii-induced-hypertension
#16
Anja Meissner, Jens Minnerup, Guadalupe Soria Rodriguez, Anna M Planas
Hypertension is a main risk factor for the development of cerebral small vessel disease (cSVD) - a major contributor to stroke and the most common cause of vascular dementia. Despite the increasing socio-economic importance arising from cSVD, currently only a few specific treatment strategies with proven efficacy are known. Fundamental to the lack of specific treatments is poor understanding of the disease pathogenesis and a lack of appropriate animal models resembling all symptoms of the human disease. However, chronic hypertensive rat models have been shown to bear similarities to most key features of cSVD...
November 22, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27859239/7-th-isn-special-neurochemistry-conference-synaptic-function-and-dysfunction-in-brain-diseases
#17
Carlos B Duarte, Ana Luisa Carvalho
This article is part of a mini review series: "Synaptic Function and Dysfunction in Brain Diseases".
November 16, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27861901/chloride-co-transporters-as-possible-therapeutic-targets-for-stroke
#18
REVIEW
Miguel A S Martín-Aragón Baudel, Amy V Poole, Mark G Darlison
Stroke is one of the major causes of death and disability worldwide. The major type of stroke is an ischaemic one, which is caused by a blockage that interrupts blood flow to the brain. There are currently very few pharmacological strategies to reduce the damage and social burden triggered by this pathology. The harm caused by the interruption of blood flow to the brain unfolds in the subsequent hours and days, so it is critical to identify new therapeutic targets that could reduce neuronal death associated with the spread of the damage...
November 15, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27861892/the-regulator-of-calcineurin-1-increases-adenine-nucleotide-translocator-1-and-leads-to-mitochondrial-dysfunctions
#19
Hui Jiang, Chen Zhang, Yu Tang, Juan Zhao, Tan Wang, Heng Liu, Xiulian Sun
The overexpression of regulator of calcineurin 1 isoform 1 (RCAN1.1) has been implicated in mitochondrial dysfunctions of Alzheimer's disease (AD); however, the mechanism linking RCAN1.1 overexpression and the mitochondrial dysfunctions remains unknown. In this study, we use human neuroblastoma SH-SY5Y cells stably expressing RCAN1.1S and rat primary neurons infected with RCAN1.1S expression lentivirus to study the association of RCAN1 with mitochondrial functions. Our study here showed that the overexpression of RCAN1...
November 15, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27859240/the-neuroprotective-effect-of-latanoprost-acts-via-klotho-mediated-suppression-of-calpain-activation-after-optic-nerve-transection
#20
Kotaro Yamamoto, Kota Sato, Masayoshi Yukita, Masayuki Yasuda, Kazuko Omodaka, Morin Ryu, Kosuke Fujita, Koji M Nishiguchi, Shigeki Machida, Toru Nakazawa
Latanoprost was first developed for use in glaucoma therapy as an ocular hypotensive agent targeting the prostaglandin F2α (FP) receptor. Subsequently, latanoprost showed a neuroprotective effect, an additional pharmacological action. However, although it is well known that latanoprost exerts an ocular hypotensive effect via the FP receptor, it is not known whether this is also true of its neuroprotective effect. Klotho was firstly identified as the gene linked to the suppression of ageing phenotype: the defect of klotho gene in mice results ageing phenotype such as hypokinesis, arteriosclerosis and short lifespan...
November 15, 2016: Journal of Neurochemistry
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