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Neuromolecular Medicine

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https://www.readbyqxmd.com/read/29335819/nmda-receptor-glun2-subtypes-control-epileptiform-events-in-the-hippocampus
#1
Pradeep Punnakkal, Deity Dominic
NMDA receptors (NMDARs) play a key role in synaptic plasticity and excitotoxicity. Subtype-specific role of NMDAR in neural disorders is an emerging area. Recent studies have revealed that mutations in NMDARs are a cause for epilepsy. Hippocampus is a known focal point for epilepsy. In hippocampus, expression of the NMDAR subtypes GluN1/GluN2A and GluN1/GluN2B is temporally regulated. However, the pharmacological significance of these subtypes is not well understood in epileptic context/models. To investigate this, epilepsy was induced in hippocampal slices by the application of artificial cerebrospinal fluid that contained high potassium but no magnesium...
January 15, 2018: Neuromolecular Medicine
https://www.readbyqxmd.com/read/29332269/behavioral-biochemical-and-molecular-characterization-of-a-parkinson-s-disease-mouse-model-using-the-neurotoxin-2-ch3-mptp-a-novel-approach
#2
Alice Laschuk Herlinger, Agihane Rodrigues Almeida, Sarah Martins Presti-Silva, Evaldo Vitor Pereira, Filipe Andrich, Rita Gomes Wanderley Pires, Cristina Martins-Silva
The neurotoxin MPTP has long been used to create a mouse model of Parkinson's disease (PD). Indeed, several MPTP analogues have been developed, including 2'-CH3-MPTP, which was shown to induce nigrostriatal DA neuronal depletion more potently than MPTP. However, no study on behavioral and molecular alterations in response to 2'-CH3-MPTP has been carried out so far. In the present work, 2'-CH3-MPTP was administered to mice (2.5, 5.0 and 10 mg/kg per injection, once a day, 5 days) and histological, biochemical, molecular and behavioral alterations were evaluated...
January 13, 2018: Neuromolecular Medicine
https://www.readbyqxmd.com/read/29307058/serum-mortalin-correlated-with-%C3%AE-synuclein-as-serum-markers-in-parkinson-s-disease-a-pilot-study
#3
Amrendra Pratap Singh, Teena Bajaj, Divya Gupta, Sundararajan Baskar Singh, Avinash Chakrawarty, Vinay Goyal, Aparajit B Dey, Sharmistha Dey
Mortalin, a mitochondrial chaperone, plays a crucial role in reducing toxicity of Lewy bodies. Earlier studies had reported that Mortalin level gets downregulated in astrocytes and other brain tissue samples in Parkinson's disease (PD). This study aims to estimate the Mortalin concentration in serum and correlate with α-synuclein (α-Syn) in PD. The concentration of Mortalin and α-Syn in serum samples of 38 PD patients and 33 control group (CG) individuals was quantified by surface plasmon resonance. The receiver operating characteristic curves were plotted to develop it as blood-based protein marker...
January 6, 2018: Neuromolecular Medicine
https://www.readbyqxmd.com/read/29305687/genetics-and-treatment-response-in-parkinson-s-disease-an-update-on-pharmacogenetic-studies
#4
REVIEW
Cristina Politi, Cinzia Ciccacci, Giuseppe Novelli, Paola Borgiani
Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by a progressive loss of dopamine neurons of the central nervous system. The disease determines a significant disability due to a combination of motor symptoms such as bradykinesia, rigidity and rest tremor and non-motor symptoms such as sleep disorders, hallucinations, psychosis and compulsive behaviors. The current therapies consist in combination of drugs acting to control only the symptoms of the illness by the replacement of the dopamine lost...
January 5, 2018: Neuromolecular Medicine
https://www.readbyqxmd.com/read/29299869/combination-therapy-with-low-dose-ivig-and-a-c1-esterase-inhibitor-ameliorates-brain-damage-and-functional-deficits-in-experimental-ischemic-stroke
#5
Xinzhi Chen, Thiruma V Arumugam, Yi-Lin Cheng, Jong-Hwan Lee, Srinivasulu Chigurupati, Mark P Mattson, Milan Basta
Acute ischemic stroke causes a high rate of deaths and permanent neurological deficits in survivors. Current interventional treatment, in the form of enzymatic thrombolysis, benefits only a small percentage of patients. Brain ischemia triggers mobilization of innate immunity, specifically the complement system and Toll-like receptors (TLRs), ultimately leading to an exaggerated inflammatory response. Here we demonstrate that intravenous immunoglobulin (IVIG), a scavenger of potentially harmful complement fragments, and C1-esterase inhibitor (C1-INH), an inhibitor of complement activation, exert a beneficial effect on the outcome of experimental brain ischemia (I) and reperfusion (R) injury induced by transient occlusion of middle cerebral artery in mice...
January 3, 2018: Neuromolecular Medicine
https://www.readbyqxmd.com/read/29218434/inhibition-of-gsk-3beta-signaling-pathway-rescues-ketamine-induced-neurotoxicity-in-neural-stem-cell-derived-neurons
#6
Jingjing Zhang, Changlei Cui, Yanhui Li, Haiyang Xu
Clinical application of anesthetic reagent, ketamine (Keta), may induce irreversible neurotoxicity in central nervous system. In this work, we utilized an in vitro model of neural stem cells-derived neurons (nSCNs) to evaluate the role of GSK-3 signaling pathway in Keta-induced neurotoxicity. Embryonic mouse-brain neural stem cells were differentiated into neurons in vitro. Keta (50 μM)-induced neurotoxicity in cultured nSCNs was monitored by apoptosis, immunohistochemical and western blot assays, respectively...
December 7, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/29098526/elevated-plasma-level-of-soluble-form-of-rage-in-ischemic-stroke-patients-with-dementia
#7
Sung-Chun Tang, Kai-Chien Yang, Chaur-Jong Hu, Hung-Yi Chiou, Chau Chung Wu, Jiann-Shing Jeng
The receptor for advanced glycation end products (RAGE) and its downstream pathways are involved in various inflammatory and immune responses. Importantly, there is soluble RAGE (sRAGE) that forms either by alternative splicing of RAGE messenger ribonucleic acid as the endogenous soluble form of RAGE (esRAGE) or by proteolytic cleavage of full-length RAGE protein. This study aimed to investigate the associations of the plasma levels of sRAGE and esRAGE in ischemic stroke (IS) patients with and without dementia...
December 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/29052076/-e-2-methoxy-4-3-4-methoxyphenyl-prop-1-en-1-yl-phenol-ameliorates-lps-mediated-memory-impairment-by-inhibition-of-stat3-pathway
#8
Ji Yeon Choi, Chul Ju Hwang, Do Yeon Lee, Sun Mi Gu, Hee Pom Lee, Dong Young Choi, Ki Wan Oh, Sang-Bae Han, Jin Tae Hong
Alzheimer's disease (AD) is pathologically characterized by an excessive accumulation of amyloid-beta (Aβ) fibrils within the brain. We tested the anti-inflammatory and anti-amyloidogenic effects of (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP), a selective signal transducer and activator of transcription 3 (STAT3) inhibitor. We examined whether MMPP (5 mg/kg in drinking water for 1 month) prevents amyloidogenesis and cognitive impairment on AD model mice induced by intraperitoneal LPS (250 μg/kg daily 7 times) injections...
December 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/29043564/the-ucp2-866g-a-polymorphism-could-be-considered-as-a-genetic-marker-of-different-functional-prognosis-in-ischemic-stroke-after-recanalization
#9
I Díaz-Maroto Cicuéndez, E Fernández-Díaz, J García-García, J Jordán, I Fernández-Cadenas, J Montaner, G Serrano-Heras, T Segura
Recent studies based on experimental animal models of stroke have suggested that uncoupling protein 2 (UCP2), an inner mitochondrial membrane protein that is thought to regulate energy metabolism and reduce reactive oxygen species generation, provides protection against reperfusion damage. We aimed to investigate whether -866G/A polymorphism in the promoter of the UCP2 gene, which enhances its transcriptional activity, is associated with functional prognosis in patients with embolic ischemic stroke after early recanalization...
December 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28918499/the-levels-of-circulating-proangiogenic-factors-in-migraineurs
#10
Slawomir Michalak, Alicja Kalinowska-Lyszczarz, Danuta Wegrzyn, Anna Thielemann, Krystyna Osztynowicz, Wojciech Kozubski
Migraine has been reported as a risk factor for ischemic stroke or cardiovascular events, and dysfunction of endothelial cells has been evidenced in migraine patients. Proangiogenic factors are potential endothelial stimulators, and their disturbances can link abnormalities of endothelium with increased risk of vascular disorders. The aim of this study was to evaluate the levels of circulating proangiogenic factors in sera of migraineurs during interictal period. Fifty-two patients aged 37.9 ± 9.6 years, fulfilling International Headache Society criteria for migraine, were included in this observational case-control study...
December 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28916896/involvement-of-il-17-in-secondary-brain-injury-after-a-traumatic-brain-injury-in-rats
#11
Tan Li, Yong-Mei Zhang, Dong Han, Rong Hua, Bing-Nan Guo, Shu-Qun Hu, Xian-Liang Yan, Tie Xu
The pro-inflammatory activity of interleukin 17, which is produced by the IL-23/IL-17 axis, has been associated with the pathogenesis of traumatic brain injury (TBI). The study investigated the potential role of IL-17 in secondary brain injury of TBI in a rat model. Our data showed that the levels of IL-17 increased from 6 h to 7 days and peaked at 3 days, in both the CNS and serum, which were consistent with the severity of secondary brain injury. The IL-23 inhibitor suberoylanilide hydroxamic acid (SAHA) treatment markedly decreased the expressions of IL-17 and apoptosis-associated proteins cleaved caspase-3 and increased the protein ratio of Bcl-2 (B cell lymphoma/leukemia-2)/Bax (Bcl-2-associated X protein)...
December 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28905220/haplotype-study-in-sca10-families-provides-further-evidence-for-a-common-ancestral-origin-of-the-mutation
#12
Giovana B Bampi, Rafael Bisso-Machado, Tábita Hünemeier, Tailise C Gheno, Gabriel V Furtado, Diego Veliz-Otani, Mario Cornejo-Olivas, Pillar Mazzeti, Maria Cátira Bortolini, Laura B Jardim, Maria Luiza Saraiva-Pereira
Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disorder characterized by progressive cerebellar ataxia and epilepsy. The disease is caused by a pentanucleotide ATTCT expansion in intron 9 of the ATXN10 gene on chromosome 22q13.3. SCA10 has shown a geographical distribution throughout America with a likely degree of Amerindian ancestry from different countries so far. Currently available data suggest that SCA10 mutation might have spread out early during the peopling of the Americas...
December 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28895049/mutation-in-gne-downregulates-peroxiredoxin-iv-altering-er-redox-homeostasis
#13
Pratibha Chanana, Gayatri Padhy, Kalpana Bhargava, Ranjana Arya
GNE myopathy is a rare neuromuscular genetic disorder characterized by early adult onset and muscle weakness due to mutation in sialic acid biosynthetic enzyme, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). More than 180 different GNE mutations are known all over the world with unclear pathomechanism. Although hyposialylation of glycoproteins is speculated to be the major cause, but cellular mechanism leading to loss of muscle mass has not yet been deciphered. Besides sialic acid biosynthesis, GNE affects other cellular functions such as cell adhesion and apoptosis...
December 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28866774/purine-biosynthesis-enzymes-in-hippocampal-neurons
#14
Julie Williamson, Ronald S Petralia, Ya-Xian Wang, Mark P Mattson, Pamela J Yao
Despite reports implicating disrupted purine metabolism in causing a wide spectrum of neurological defects, the mechanistic details of purine biosynthesis in neurons are largely unknown. As an initial step in filling that gap, we examined the expression and subcellular distribution of three purine biosynthesis enzymes (PFAS, PAICS and ATIC) in rat hippocampal neurons. Using immunoblotting and high-resolution light and electron microscopic analysis, we find that all three enzymes are broadly distributed in hippocampal neurons with pools of these enzymes associated with mitochondria...
December 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28852993/stat4-polymorphisms-are-associated-with-neuromyelitis-optica-spectrum-disorders
#15
Ziyan Shi, Qin Zhang, Hongxi Chen, Zhiyun Lian, Ju Liu, Huiru Feng, Xiaohui Miao, Qin Du, Hongyu Zhou
STAT4 plays a crucial role in the functioning of the innate and adaptive immune cells and has been identified as a susceptibility gene in numerous autoimmune disorders. However, its association with neuromyelitis optica spectrum disorders (NMOSD) remains uncertain. Here, we performed a case-control study to determine whether STAT4 contributed to the risk of NMOSD. We tested five STAT4 SNPs in 233 patients with established NMOSD and 492 healthy controls. Chi-square tests and logistic regression analyses were performed with four genetic models, including allelic, additive, dominant, and recessive models, to identify associations with NMOSD...
December 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28828577/scavenger-receptor-a-mediates-the-clearance-and-immunological-screening-of-mda-modified-antigen-by-m2-type-macrophages
#16
Andreas Warnecke, Sonja Abele, Sravani Musunuri, Jonas Bergquist, Robert A Harris
In this study, we investigated the uptake of malondialdehyde (MDA)-modified myelin oligodendrocyte glycoprotein (MOG) in the context of lipid peroxidation and its implications in CNS autoimmunity. The use of custom-produced fluorescently labeled versions of MOG or MDA-modified MOG enabled us to study and quantify the uptake by different macrophage populations and to identify the responsible receptor, namely SRA. The SRA-mediated uptake of MDA-modified MOG is roughly tenfold more efficient compared to that of the native form...
December 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28822073/isorhynchophylline-attenuates-mpp-induced-apoptosis-through-endoplasmic-reticulum-stress-and-mitochondria-dependent-pathways-in-pc12-cells-involvement-of-antioxidant-activity
#17
Xiao-Ming Li, Xiao-Jie Zhang, Miao-Xian Dong
Endoplasmic reticulum stress (ERS) and mitochondrial dysfunctions are thought to be involved in the dopaminergic neuronal death in Parkinson's disease (PD). In this study, we found that isorhynchophylline (IRN) significantly attenuated 1-methyl-4-phenylpyridinium (MPP(+))-induced apoptotic cell death and oxidative stress in PC12 cells. IRN markedly reduced MPP(+)-induced-ERS responses, indicative of inositol-requiring enzyme 1 (IRE1) phosphorylation and caspase-12 activation. Furthermore, IRN inhibits MPP(+)-triggered apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal Kinase (JNK) signaling-mediated mitochondria-dependent apoptosis pathway...
December 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28795310/association-between-nos1-gene-polymorphisms-and-schizophrenia-in-asian-and-caucasian-populations-a-meta-analysis
#18
Shiek S S J Ahmed, R S Akram Husain, Suresh Kumar, V Ramakrishnan
Schizophrenia is a complex psychiatric disorder characterized by memory impairments with delusions and hallucinations. Several investigations have focused on determining the association between NOS1 (nitric oxide synthase-1) polymorphisms and risk of schizophrenia (SZ). However, the association of rs2682826, rs3782206, rs499776, rs3782219, rs41279104, rs3782221, rs1879417, rs4767540, rs561712, and rs6490121 polymorphisms with schizophrenia remains inconclusive. We performed a systematic meta-analysis for each polymorphism to determine its association with SZ by calculating their pooled odds ratio and 95% confidence intervals...
September 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28779377/combination-of-epa-with-carotenoids-and-polyphenol-synergistically-attenuated-the-transformation-of-microglia-to-m1-phenotype-via-inhibition-of-nf-%C3%AE%C2%BAb
#19
Nurit Hadad, Rachel Levy
Microglia activation toward the M1 phenotype has been reported to contribute to the neurodegenerative processes and cognition alterations due to the release of pro-inflammatory mediators and cytokines. The aim of the present research was to assess the effectiveness of free fatty acids omega-3 preparations: eicosapentaenoic acid (EPA) or/and docosahexaenoic acid (DHA), carotenoids and phenolics combinations, in inhibiting the release of inflammatory mediators from activated microglia. Preincubation of BV-2 microglia cells with each of the FFAs omega-3 preparations in a range of 0...
September 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28766254/vegf-mediated-cognitive-and-synaptic-improvement-in-chronic-cerebral-hypoperfusion-rats-involves-autophagy-process
#20
Ling Wang, Jingyu Wang, Faqi Wang, Chunhua Liu, Xuening Yang, Jiajia Yang, Dong Ming
Chronic cerebral hypoperfusion (CCH) is associated with various neurodegenerative diseases characterized by cognitive impairment. Dozens of studies including ours have indicated that exogenous administration of vascular endothelial growth factor (VEGF) could exert effective cognitive protection during ischemia. Nevertheless, the underlying mechanism has not been well clarified. To address this issue, we explored the synaptic mechanisms in vivo since hippocampal synaptic function is essential to the learning and memory process...
September 2017: Neuromolecular Medicine
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