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https://www.readbyqxmd.com/read/28652929/tnf-%C3%AE-and-beyond-rapid-mitochondrial-dysfunction-mediates-tnf-%C3%AE-induced-neurotoxicity
#1
Ashley E Russell, Danielle N Doll, Saumyendra N Sarkar, James W Simpkins
This short communication describes our research which demonstrates that TNF-α causes a rapid decline in mitochondrial function, leading to neuronal cell death. As such, this neurotoxic proinflammatory cytokine may play a role in brain damage from stroke and neurodegeneration in chronic conditions such as Alzheimer's disease (AD) and Parkinson's disease. We have extended this initial observation by demonstrating that TNF-α stimulates a microRNA (miR-34a) which we have shown reduces five key proteins in the mitochondrial electron transport chain through base-pair complementarity...
December 2016: Journal of Clinical & Cellular Immunology
https://www.readbyqxmd.com/read/28648936/diagnostic-pathology-of-alzheimer-s-disease-from-routine-microscopy-to-immunohistochemistry-and-experimental-correlations
#2
Gerard Nuovo, Bernard Paniccia, Louisa Mezache, Maria Quiñónez, James Williams, Paige Vandiver, Paolo Fadda, Vicky Amann
The absence of any histologic correlate for Alzheimer's disease despite its commonness and severe clinical sequelae may offers clues to its etiology. Recent evidence strongly suggests that the central event of this disease is the hyperphosphorylation of neuronal tau protein and not the beta amyloid precipitates. In each case, essential and soluble neuronal proteins derivatives form insoluble aggregates that can readily be detected by immunohistochemistry using antibodies specific for the misfolded proteins...
June 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/28646119/rest-suppression-mediates-neural-conversion-of-adult-human-fibroblasts-via-microrna-dependent-and-independent-pathways
#3
Janelle Drouin-Ouellet, Shong Lau, Per Ludvik Brattås, Daniella Rylander Ottosson, Karolina Pircs, Daniela A Grassi, Lucy M Collins, Romina Vuono, Annika Andersson Sjöland, Gunilla Westergren-Thorsson, Caroline Graff, Lennart Minthon, Håkan Toresson, Roger A Barker, Johan Jakobsson, Malin Parmar
Direct conversion of human fibroblasts into mature and functional neurons, termed induced neurons (iNs), was achieved for the first time 6 years ago. This technology offers a promising shortcut for obtaining patient- and disease-specific neurons for disease modeling, drug screening, and other biomedical applications. However, fibroblasts from adult donors do not reprogram as easily as fetal donors, and no current reprogramming approach is sufficiently efficient to allow the use of this technology using patient-derived material for large-scale applications...
June 23, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28640911/evolution-of-microrna-in-primates
#4
Jennifer C McCreight, Sean E Schneider, Damien B Wilburn, Willie J Swanson
MicroRNA play an important role in post-transcriptional regulation of most transcripts in the human genome, but their evolution across the primate lineage is largely uncharacterized. A particular miRNA can have one to thousands of messenger RNA targets, establishing the potential for a small change in sequence or overall miRNA structure to have profound phenotypic effects. However, the majority of non-human primate miRNA is predicted solely by homology to the human genome and lacks experimental validation. In the present study, we sequenced thirteen species representing a wide range of the primate phylogeny...
2017: PloS One
https://www.readbyqxmd.com/read/28637335/astrocyte-produced-mir-146a-as-a-mediator-of-motor-neuron-loss-in-spinal-muscular-atrophy
#5
Samantha L Sison, Teresa N Patitucci, Emily R Seminary, Eric Villalon, Christian L Lorson, Allison D Ebert
Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality, is caused by loss of the survival motor neuron-1 (SMN1) gene, which leads to motor neuron loss, muscle atrophy, respiratory distress, and death. Motor neurons exhibit the most profound loss, but the mechanisms underlying disease pathogenesis are not fully understood. Recent evidence suggests that motor neuron extrinsic influences, such as those arising from astrocytes, contribute to motor neuron malfunction and loss. Here we investigated both loss-of-function and toxic gain-of-function astrocyte mechanisms that could play a role in SMA pathology...
June 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28636953/dicer-deficiency-differentially-impacts-microglia-of-the-developing-and-adult-brain
#6
Diana Varol, Alexander Mildner, Thomas Blank, Anat Shemer, Neta Barashi, Simon Yona, Eyal David, Sigalit Boura-Halfon, Yifat Segal-Hayoun, Louise Chappell-Maor, Hadas Keren-Shaul, Dena Leshkowitz, Eran Hornstein, Martin Fuhrmann, Ido Amit, Nicola Maggio, Marco Prinz, Steffen Jung
Microglia seed the embryonic neuro-epithelium, expand and actively sculpt neuronal circuits in the developing central nervous system, but eventually adopt relative quiescence and ramified morphology in the adult. Here, we probed the impact of post-transcriptional control by microRNAs (miRNAs) on microglial performance during development and adulthood by generating mice lacking microglial Dicer expression at these distinct stages. Conditional Dicer ablation in adult microglia revealed that miRNAs were required to limit microglial responses to challenge...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28627974/microrna-132-protects-hippocampal-neurons-against-oxygen-glucose-deprivation-induced-apoptosis
#7
Zu-Zhen Sun, Zhan-Yun Lv, Wen-Jing Tian, Yan Yang
Hypoxic-ischemic brain injury (HIBI) results in death or long-term neurologic impairment in both adults and children. In this study, we investigated the effects of microRNA-132 (miR-132) dysregulation on oxygen-glucose deprivation (OGD)-induced apoptosis in fetal rat hippocampal neurons, in order to reveal the therapeutic potential of miR-132 on HIBI. MiR-132 dysregulation was induced prior to OGD exposure by transfection of primary fetal rat hippocampal neurons with miR-132 mimic or miR-132 inhibitor. The effects of miR-132 overexpression and suppression on OGD-stimulated hippocampal neurons were evaluated by detection of cell viability, apoptotic cells rate, and the expression of apoptosis-related proteins...
June 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28624203/exosome-mediated-delivery-of-mir-124-promotes-neurogenesis-after-ischemia
#8
Jialei Yang, Xiufen Zhang, Xiangjie Chen, Lei Wang, Guodong Yang
The intrinsic ability of neurogenesis after stroke has been proven weak, which results in insufficient repair of injury in the nerve system. Recent studies suggest multiple microRNAs (miRNAs) are involved in the neuroremodeling process. Targeted miRNAs delivery for amplification of neurogenesis is promising in promoting the prognosis after ischemia. Here, we showed that modified exosomes, with rabies virus glycoprotein (RVG) fused to exosomal protein lysosome-associated membrane glycoprotein 2b (Lamp2b), could efficiently deliver miR-124 to the infarct site...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28623098/acquired-inhibition-of-microrna-124-protects-against-spinal-cord-ischemia-reperfusion-injury-partially-through-a-mitophagy-dependent-pathway
#9
Kun Liu, Lihui Yan, Xiaojing Jiang, Yang Yu, Hongbo Liu, Tianxiang Gu, Enyi Shi
OBJECTIVE: Mitophagy results in selective clearance of damaged mitochondria. We investigated whether mitophagy was involved in the neuroprotection by inhibiting microRNA (miRNA)-124 on ischemic spinal cords. METHODS: Inhibition of miRNA-124 was conducted by intrathecal injection of lentivirus vectors containing antagomiR-124. Spinal cord ischemia was induced in rats by crossclamping the descending aorta just distal to the left subclavian artery for 14 minutes. Hind-limb motor function was assessed with the motor deficit index (MDI)...
May 23, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28619522/integrated-analysis-of-paraquat-induced-micrornas-mrnas-changes-in-human-neural-progenitor-cells
#10
Mengling Yan, Tingting Dou, Wen Lv, Xinjin Wang, Lina Zhao, Xiuli Chang, Zhijun Zhou
Paraquat (PQ), one of the most widely used fast-acting and non-selective herbicides in the world is believed to act as a neurotoxicant, which increases the risk of developing Parkinson's disease (PD) by selectively impairing dopaminergic neurons. However, the mechanism of PQ on neural progenitor cells remains unclear. As regulator of mRNA expression, miRNA play a crucial role in neurotoxicity. Based on our previous study, we chose 10μM PQ, which induced ROS production and inhibited proliferation but not reduced the cell viability...
June 12, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28615713/exosomal-micrornas-in-giant-panda-ailuropoda-melanoleuca-breast-milk-potential-maternal-regulators-for-the-development-of-newborn-cubs
#11
Jideng Ma, Chengdong Wang, Keren Long, Hemin Zhang, Jinwei Zhang, Long Jin, Qianzi Tang, Anan Jiang, Xun Wang, Shilin Tian, Li Chen, Dafang He, Desheng Li, Shan Huang, Zhi Jiang, Mingzhou Li
The physiological role of miRNAs is widely understood to include fine-tuning the post-transcriptional regulation of a wide array of biological processes. Extensive studies have indicated that exosomal miRNAs in the bodily fluids of various organisms can be transferred between living cells for the delivery of gene silencing signals. Here, we illustrated the expression characteristics of exosomal miRNAs in giant panda breast milk during distinct lactation periods and highlighted the enrichment of immune- and development-related endogenous miRNAs in colostral and mature giant panda milk...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28614186/mir-34c-5p-functions-as-pronociceptive-microrna-in-cancer-pain-by-targeting-cav2-3-containing-calcium-channels
#12
Jagadeesh Gandla, Santosh Kumar Lomada, Jianning Lu, Rohini Kuner, Kiran Kumar Bali
Pathophysiological mechanisms underlying pain associated with cancer are poorly understood. microRNAs are a class of non-coding RNAs with emerging functional importance in chronic pain. In a genome-wide screen for microRNAs regulated in dorsal root ganglia (DRG) neurons in a mouse model of bone metastatic pain, we identified miR-34c-5p as a functionally important pronociceptive microRNA. Despite these functional insights and therapeutic potential for miR-34c-5p, its molecular mechanism of action in peripheral sensory neurons remains unknown...
June 9, 2017: Pain
https://www.readbyqxmd.com/read/28612726/-micrornas-new-players-in-the-hypothalamic-control-of-fertility
#13
Andrea Messina, Fanny Langlet, Vincent Prevot
MicroRNAs are small non-coding RNAs that modulate gene expression post-transcriptionally. Discovered more than 15 years ago, their functions start to be unraveled. Increasing evidence points to an important functional role of microRNAs in brain development. In particular, miRNAs have recently been established to play a vital role in the mechanisms underlying the infantile rise in gonadotropin-releasing hormone (GnRH) production by neurons in the hypothalamus, a phenomenon necessary for the onset of puberty in mammals...
May 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28612258/downregulated-glia-interplay-and-increased-mirna-155-as-promising-markers-to-track-als-at-an%C3%A2-early-stage
#14
Carolina Cunha, Catarina Santos, Cátia Gomes, Adelaide Fernandes, Alexandra Marçal Correia, Ana Maria Sebastião, Ana Rita Vaz, Dora Brites
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of unknown cause. Absence of specific targets and biomarkers compromise the development of new therapeutic strategies and of innovative tools to stratify patients and assess their responses to treatment. Here, we investigate changes in neuroprotective-neuroinflammatory actions in the spinal cord of SOD1 (G93A) mice, at presymptomatic and symptomatic stages to identify stage-specific biomarkers and potential targets. Results showed that in the presymptomatic stage, there are alterations in both astrocytes and microglia, which comprise decreased expression of GFAP and S100B and upregulation of GLT-1, as well as reduced expression of CD11b, M2-phenotype markers, and a set of inflammatory mediators...
June 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28611587/downregulation-of-microrna-193b-3p-promotes-autophagy-and-cell-survival-by-targeting-tsc1-mtor-signaling-in-nsc-34-cells
#15
ChunYu Li, YongPing Chen, XuePing Chen, QianQian Wei, Bei Cao, HuiFang Shang
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the death of upper and lower motor neurons. MicroRNAs (miRNAs) are reported to be closely related to the development of ALS. However, the precise functions of miRNAs in the pathogenesis of ALS remain largely unknown. In previous studies, we determined that miRNA-193b-3p was significantly downregulated in patients with sporadic ALS (sALS). Here, we observed that miRNA-193b-3p was downregulated in the SOD1(G93A) mouse model of ALS and promoted cell death in NSC-34 cells...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28607431/cerebrospinal-fluid-micrornas-are-potential-biomarkers-of-temporal-lobe-epilepsy-and-status-epilepticus
#16
Rana Raoof, Eva M Jimenez-Mateos, Sebastian Bauer, Björn Tackenberg, Felix Rosenow, Johannes Lang, Müjgan Dogan Onugoren, Hajo Hamer, Tessa Huchtemann, Peter Körtvélyessy, Niamh M C Connolly, Shona Pfeiffer, Jochen H M Prehn, Michael A Farrell, Donncha F O'Brien, David C Henshall, Catherine Mooney
There is a need for diagnostic biomarkers of epilepsy and status epilepticus to support clinical examination, electroencephalography and neuroimaging. Extracellular microRNAs may be potentially ideal biomarkers since some are expressed uniquely within specific brain regions and cell types. Cerebrospinal fluid offers a source of microRNA biomarkers with the advantage of being in close contact with the target tissue and sites of pathology. Here we profiled microRNA levels in cerebrospinal fluid from patients with temporal lobe epilepsy or status epilepticus, and compared findings to matched controls...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28597341/in-silico-prediction-and-validation-of-gfap-as-an-mir-3099-target-in-mouse-brain
#17
Shahidee Zainal Abidin, Jia-Wen Leong, Marzieh Mahmoudi, Norshariza Nordin, Syahril Abdullah, Pike-See Cheah, King-Hwa Ling
MicroRNAs are small non-coding RNAs that play crucial roles in the regulation of gene expression and protein synthesis during brain development. MiR-3099 is highly expressed throughout embryogenesis, especially in the developing central nervous system. Moreover, miR-3099 is also expressed at a higher level in differentiating neurons in vitro, suggesting that it is a potential regulator during neuronal cell development. This study aimed to predict the target genes of miR-3099 via in-silico analysis using four independent prediction algorithms (miRDB, miRanda, TargetScan, and DIANA-micro-T-CDS) with emphasis on target genes related to brain development and function...
June 8, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28595952/trans-resveratrol-enriched-maternal-diet-protects-the-immature-hippocampus-from-perinatal-asphyxia-in-rats
#18
Sebastian Isac, Anca Maria Panaitescu, Ana Spataru, Mara Iesanu, Alexandra Totan, Amalia Udriste, Natalia Cucu, Gheorghe Peltecu, Leon Zagrean, Ana-Maria Zagrean
Trans-resveratrol (tRESV), a polyphenol with antioxidant properties, is common in many food sources, hence easily accessible for study as a maternal dietary supplement in perinatal asphyxia (PA). Hypoxic-ischemic encephalopathy secondary to PA affects especially vulnerable brain areas such as hippocampus and is a leading cause of neonatal morbidity. The purpose of this study is to identify new epigenetic mechanisms of brain inflammation and injury related to PA and to explore the benefit of tRESV enriched maternal diet...
June 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28592747/roles-of-hypoxia-response-in-retinal-development-and-pathophysiology
#19
Toshihide Kurihara
The hypoxia response is a fundamental phenomenon mainly regulated by hypoxia-inducible factors (HIFs). For more than a decade, we have investigated and revealed the roles of the hypoxia response in the development, physiology, and pathophysiology of the retina by generating and utilizing cell-type-specific conditional knockout mice. To investigate the functions of genes related to the hypoxia response in cells composing the retina, we generated various mouse lines that lack HIFs and/or related genes specifically in retinal neurons, astrocytes, myeloid cells, or retinal pigment epithelium cells...
June 6, 2017: Keio Journal of Medicine
https://www.readbyqxmd.com/read/28582325/astroglial-microrna-219-5p-in-the-ventral-tegmental-area-regulates-nociception-in-rats
#20
Song Zhang, Xiao-Na Yang, Ting Zang, Jun Luo, Zhiqiang Pan, Lei Wang, He Liu, Di Liu, Yan-Qiang Li, Yao-Dong Zhang, Hongxing Zhang, Hai-Lei Ding, Jun-Li Cao
BACKGROUND: The authors previously reported that noncoding microRNA miR-219-5p is down-regulated in the spinal cord in a nociceptive state. The ventral tegmental area also plays critical roles in modulating nociception, although the underlying mechanism remains unknown. The authors hypothesized that miR-219-5p in the ventral tegmental area also may modulate nociception. METHODS: The authors studied the bidirectional regulatory role of ventral tegmental area miR-219-5p in a rat complete Freund's adjuvant model of inflammatory nociception by measuring paw withdrawal latencies...
June 5, 2017: Anesthesiology
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