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Molecular Neurobiology

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https://www.readbyqxmd.com/read/30242727/myelin-water-fraction-imaging-reveals-hemispheric-asymmetries-in-human-white-matter-that-are-associated-with-genetic-variation-in-plp1
#1
Sebastian Ocklenburg, Catrona Anderson, Wanda M Gerding, Christoph Fraenz, Caroline Schlüter, Patrick Friedrich, Maximilian Raane, Burkhard Mädler, Lara Schlaffke, Larissa Arning, Jörg T Epplen, Onur Güntürkün, Christian Beste, Erhan Genç
Myelination of axons in the central nervous system is critical for human cognition and behavior. The predominant protein in myelin is proteolipid protein-making PLP1, the gene that encodes for proteolipid protein, one of the primary candidate genes for white matter structure in the human brain. Here, we investigated the relation of genetic variation within PLP1 and white matter microstructure as assessed with myelin water fraction imaging, a neuroimaging technique that has the advantage over conventional diffusion tensor imaging in that it allows for a more direct assessment of myelin content...
September 21, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/30238390/visualization-of-the-breakdown-of-the-axonal-transport-machinery-a-comparative-ultrastructural-and-immunohistochemical-approach
#2
Sebastian Rühling, Franziska Kramer, Selina Schmutz, Sandra Amor, Zhan Jiangshan, Christoph Schmitz, Markus Kipp, Tanja Hochstrasser
Axonal damage is a major factor contributing to disease progression in multiple sclerosis (MS) patients. On the histological level, acute axonal injury is most frequently analyzed by anti-amyloid precursor protein immunohistochemistry. To what extent this method truly detects axonal injury, and whether other proteins and organelles are as well subjected to axonal transport deficits in demyelinated tissues is not known. The aim of this study was to correlate ultrastructural morphology with the immunohistochemical appearance of acute axonal injury in a model of toxin-induced oligodendrocyte degeneration...
September 21, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/30238389/modeling-alzheimer-s-disease-by-induced-pluripotent-stem-cells-carrying-app-d678h-mutation
#3
Kuo-Hsuan Chang, Guey-Jen Lee-Chen, Ching-Chang Huang, Jia-Li Lin, Yi-Jing Chen, Pei-Chi Wei, Yen-Shi Lo, Chin-Fa Yao, Ming-Wei Kuo, Chiung-Mei Chen
Alzheimer's disease (AD), probably caused by abnormal accumulation of β-amyloid (Aβ) and aberrant phosphorylation of tau, is the most common cause of dementia among older people. Generation of patient-specific neurons by induced pluripotent stem cell (iPSC) technology facilitates exploration of the disease features in live human neurons from AD patients. In this study, we generated iPSCs from two familial AD patients carrying a heterozygous D678H mutation in the APP gene (AD-iPSCs). The neurons derived from our AD-iPSCs demonstrated aberrant accumulation of intracellular and secreted Aβ42 and Aβ40, reduction of serine 9 phosphorylation in glycogen synthase kinase 3β (GSK3β) hyperphosphorylation of threonine 181 and serine 396 in tau protein, impaired neurite outgrowth, downregulation of synaptophysin, and increased caspase 1 activity...
September 20, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/30238388/alterations-in-the-serotonin-and-dopamine-pathways-by-cystathionine-beta-synthase-overexpression-in-murine-brain
#4
J London, F K Ndiaye, L C Bui, B Souchet, F Daubigney, C Magnan, S Luquet, J Dairou, N Janel, C Rouch
Cystathionine beta synthase (CBS) is one of the 225 genes on chromosome 21 (HSA 21) that are triplicated in persons with trisomy 21 (Down syndrome). Although most triplicate HSA21 genes have their orthologous genes on murine chromosome 16, the murine ortholog of hCBS is on murine chromosome 17 and thus is not present in the well-studied Ts65Dn mouse model of trisomy 21. Persons with trisomy 21 (T21) present deficits in neurotransmission and exhibit early brain aging that can partially be explained by monoamine neurotransmitter alterations...
September 20, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/30232777/diltiazem-promotes-regenerative-axon-growth
#5
Eric A Huebner, Stéphane Budel, Zhaoxin Jiang, Takao Omura, Tammy Szu-Yu Ho, Lee Barrett, Janie S Merkel, Luis M Pereira, Nick A Andrews, Xingxing Wang, Bhagat Singh, Kush Kapur, Michael Costigan, Stephen M Strittmatter, Clifford J Woolf
Axotomy results in permanent loss of function after brain and spinal cord injuries due to the minimal regenerative propensity of the adult central nervous system (CNS). To identify pharmacological enhancers of axon regeneration, 960 compounds were screened for cortical neuron axonal regrowth using an in vitro cortical scrape assay. Diltiazem, verapamil, and bromopride were discovered to facilitate axon regeneration in rat cortical cultures, in the presence of chondroitin sulfate proteoglycans (CSPGs). Diltiazem, an L-type calcium channel blocker (L-CCB), also promotes axon outgrowth in adult primary mouse dorsal root ganglion (DRG) and induced human sensory (iSensory) neurons...
September 19, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/30229438/sodium-butyrate-exerts-neuroprotective-effects-in-spinal-cord-injury
#6
M Lanza, M Campolo, G Casili, A Filippone, I Paterniti, S Cuzzocrea, Emanuela Esposito
Sodium butyrate (SB) is a dietary microbial fermentation product and serves as an important neuromodulator in the central nervous system. Recent experimental evidence has suggested potential therapeutic applications for butyrate, including its utility in treating metabolic and inflammatory diseases. The aim of the present study was to evaluate the potential beneficial effects of SB in a mouse model of spinal cord injury (SCI) and its possible mechanism of action. SCI was induced by extradural compression for 1 min of the spinal cord at the T6-7 level using an aneurysm clip, and SB (10-30-100 mg/kg) was administered by oral gavage 1 and 6 h after SCI...
September 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/30225776/amyloid-%C3%AE-peptide-compromises-neural-stem-cell-fate-by-irreversibly-disturbing-mitochondrial-oxidative-state-and-blocking-mitochondrial-biogenesis-and-dynamics
#7
Maria Filipe Ribeiro, Tânia Genebra, Ana Cristina Rego, Cecília M P Rodrigues, Susana Solá
Alzheimer's disease (AD) is the most common neurodegenerative disease and is characterized by the accumulation of amyloid β peptide (Aβ). Although most AD mouse models present a decline in neurogenesis, they express mutated genes which regulate neurogenesis per se and are not present in most AD patients, thus masking the real impact of Aβ on adult neurogenesis. Mitochondrion, a well-known target of Aβ in neurons, is a main regulator of neural stem cell (NSC) fate. Here, we aimed to investigate the impact of Aβ on NSC mitochondria and cell fate decisions, namely whether and how Aβ affects neurogenesis...
September 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/30225775/fragile-x-and-app-a-decade-in-review-a-vision-for-the-future
#8
REVIEW
Cara J Westmark
Fragile X syndrome (FXS) is a devastating developmental disability that has profound effects on cognition, behavior, and seizure susceptibility. There are currently no treatments that target the underlying cause of the disorder, and recent clinical trials have been unsuccessful. In 2007, seminal work demonstrated that amyloid-beta protein precursor (APP) is dysregulated in Fmr1KO mice through a metabotropic glutamate receptor 5 (mGluR5 )-dependent pathway. These findings raise the hypotheses that: (1) APP and/or APP metabolites are potential therapeutic targets as well as biomarkers for FXS and (2) mGluR5 inhibitors may be beneficial in the treatment of Alzheimer's disease...
September 17, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/30225774/sprouty2-a-novel-therapeutic-target-in-the-nervous-system
#9
REVIEW
Barbara Hausott, Lars Klimaschewski
Clinical trials applying growth factors to alleviate symptoms of patients with neurological disorders have largely been unsuccessful in the past. As an alternative approach, growth factor receptors or components of their signal transduction machinery may be targeted directly. In recent years, the search for intracellular signaling integrator downstream of receptor tyrosine kinases provided valuable novel substrates. Among them are the Sprouty proteins which mainly act as inhibitors of growth factor-dependent neuronal and glial signaling pathways...
September 17, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/30220058/choline-rescues-behavioural-deficits-in-a-mouse-model-of-rett-syndrome-by-modulating-neuronal-plasticity
#10
Eunice W M Chin, Wee Meng Lim, Dongliang Ma, Francisco J Rosales, Eyleen L K Goh
Rett syndrome (RTT) is a postnatal neurodevelopmental disorder that primarily affects girls, with 95% of RTT cases resulting from mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Choline, a dietary micronutrient found in most foods, has been shown to be important for brain development and function. However, the exact effects and mechanisms are still unknown. We found that 13 mg/day (1.7 × required daily intake) of postnatal choline treatment to Mecp2-conditional knockout mice rescued not only deficits in motor coordination, but also their anxiety-like behaviour and reduced social preference...
September 15, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/30218401/correction-to-overexpression-of-protein-kinase-inhibitor-alpha-reverses-rat-low-voluntary-running-behavior
#11
Kolter B Grigsby, Gregory N Ruegsegger, Thomas E Childs, Frank W Booth
The original version of this article unfortunately contained mistake in Table 2 to where two directionality arrows were inverted.
September 15, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/30218400/molecular-association-of-glia-maturation-factor-with-the-autophagic-machinery-in-rat-dopaminergic-neurons-a-role-for-endoplasmic-reticulum-stress-and-mapk-activation
#12
Govindhasamy Pushpavathi Selvakumar, Shankar S Iyer, Duraisamy Kempuraj, Mohammad Ejaz Ahmed, Ramasamy Thangavel, Iuliia Dubova, Sudhanshu P Raikwar, Smita Zaheer, Asgar Zaheer
Parkinson's disease (PD) is one of the several neurodegenerative diseases where accumulation of aggregated proteins like α-synuclein occurs. Dysfunction in autophagy leading to this protein build-up and subsequent dopaminergic neurodegeneration may be one of the causes of PD. The mechanisms that impair autophagy remain poorly understood. 1-Methyl-4-phenylpiridium ion (MPP+ ) is a neurotoxin that induces experimental PD in vitro. Our studies have shown that glia maturation factor (GMF), a brain-localized inflammatory protein, induces dopaminergic neurodegeneration in PD and that suppression of GMF prevents MPP+ -induced loss of dopaminergic neurons...
September 14, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/30215159/kinesins-motor-proteins-as-novel-target-for-the-treatment-of-chronic-pain
#13
REVIEW
P A Shantanu, Dilip Sharma, Monika Sharma, Shivani Vaidya, Kuhu Sharma, Kiran Kalia, Yuan-Xiang Tao, Amit Shard, Vinod Tiwari
Kinesins are one of the neoteric and efficacious targets recently reported to play an important role in the initiation and progression of chronic pain. Kinesins are anterograde microtubule-based motor proteins that are involved in trafficking of receptors including nociceptors and progression of pain. The specific kinesin and regulatory proteins interplay is crucial for the delivery of nociceptors to the synapse. If this complex and less understood interplay is inhibited, it may result in a decrease in central sensitization, and thus attenuation of pain...
September 13, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/30215158/trpm2-ablation-accelerates-protein-aggregation-by-impaired-adpr-and-autophagic-clearance-in-the-brain
#14
Yongwoo Jang, Byeongjun Lee, Hyungsup Kim, Seungmoon Jung, Sung Hoon Lee, So-Young Lee, Ji Hyun Jeon, In-Beom Kim, Seo-Ho Lee, Byung-Ju Kim, Uh-Hyun Kim, Yunjong Lee, Sung Min Kim, Daejong Jeon, Uhtaek Oh
TRPM2 a cation channel is also known to work as an enzyme that hydrolyzes highly reactive, neurotoxic ADP-ribose (ADPR). Although ADPR is hydrolyzed by NUT9 pyrophosphatase in major organs, the enzyme is defective in the brain. The present study questions the role of TRPM2 in the catabolism of ADPR in the brain. Genetic ablation of Trpm2 results in the disruption of ADPR catabolism that leads to the accumulation of ADPR and reduction in AMP. Trpm2-/- mice elicit the reduction in autophagosome formation in the hippocampus...
September 13, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/30209774/cerebrospinal-fluid-ceruloplasmin-haptoglobin-and-vascular-endothelial-growth-factor-are-associated-with-neurocognitive-impairment-in-adults-with-hiv-infection
#15
A R Kallianpur, H Gittleman, S Letendre, R Ellis, J S Barnholtz-Sloan, W S Bush, R Heaton, D C Samuels, D R Franklin, D Rosario-Cookson, D B Clifford, A C Collier, B Gelman, C M Marra, J C McArthur, J A McCutchan, S Morgello, I Grant, D Simpson, J R Connor, T Hulgan
Dysregulated iron transport and a compromised blood-brain barrier are implicated in HIV-associated neurocognitive disorders (HAND). We quantified the levels of proteins involved in iron transport and/or angiogenesis-ceruloplasmin, haptoglobin, and vascular endothelial growth factor (VEGF)-as well as biomarkers of neuroinflammation, in cerebrospinal fluid (CSF) from 405 individuals with HIV infection and comprehensive neuropsychiatric assessments. Associations with HAND [defined by a Global Deficit Score (GDS) ≥ 0...
September 12, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/30209773/correction-to-zika-virus-and-the-metabolism-of-neuronal-cells
#16
Hussin A Rothan, Shengyun Fang, Mahesh Mohan, Siddappa N Byrareddy
The original version of this article unfortunately contained mistake.
September 12, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/30209772/nrf2-mediated-system-x-c-activation-in-astroglial-cells-is-involved-in-hiv-1-tat-induced-neurotoxicity
#17
Roberta Mastrantonio, Veronica D'Ezio, Marco Colasanti, Tiziana Persichini
HIV-associated neurocognitive disorders (HANDs) affect a large part of HIV-infected patients, despite highly active antiretroviral therapy. HANDs occur in the absence of a direct infection of neurons. Nevertheless, viral proteins (e.g., Tat) are capable to cause neuronal dysfunction via oxidative stress, but the cellular pathways leading to HANDs are not yet fully defined. Here, we investigated the effects of Tat on Nrf2-mediated antioxidant response and system xc - expression in U373 human astroglial cells...
September 12, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/30203263/persistent-lin28-expression-impairs-neurite-outgrowth-and-cognitive-function-in-the-developing-mouse-neocortex
#18
Hyun-Jong Jang, Joo Youn Kim, Seong Yun Kim, Kyung-Ok Cho
Many neurodevelopmental disorders feature learning and memory difficulties. Regulation of neurite outgrowth during development is critical for neural plasticity and memory function. Here, we show a novel regulator of neurite outgrowth during cortical neurogenesis, Lin28, which is an RNA-binding protein. Persistent Lin28 upregulation by in utero electroporation at E14.5 resulted in neurite underdevelopment during cortical neurogenesis. We also showed that Lin28-overexpressing cells had an attenuated response to excitatory inputs and altered membrane properties including higher input resistance, slower action potential repolarization, and smaller hyperpolarization-activated cation currents, supporting impaired neuronal functionality in Lin28-electroporated mice...
September 10, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/30196395/transcriptomic-analysis-reveals-sex-dependent-expression-patterns-in-the-basolateral-amygdala-of-dominant-and-subordinate-animals-after-acute-social-conflict
#19
Katharine E McCann, David M Sinkiewicz, Anna M Rosenhauer, Linda Q Beach, Kim L Huhman
The basolateral amygdala (BLA) is a critical nucleus mediating behavioral responses after exposure to acute social conflict. Male and female Syrian hamsters both readily establish a stable dominant-subordinate relationship among same-sex conspecifics, and the goal of the current study was to determine potential underlying genetic mechanisms in the BLA facilitating the establishment of social hierarchy. We sequenced the BLA transcriptomes of dominant, subordinate, and socially neutral males and females, and using de novo assembly techniques and gene network analyses, we compared these transcriptomes across social status within each sex...
September 8, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/30196394/suppressing-tau-aggregation-and-toxicity-by-an-anti-aggregant-tau-fragment
#20
Ghulam Jeelani Pir, Bikash Choudhary, Senthilvelrajan Kaniyappan, Ram Reddy Chandupatla, Eckhard Mandelkow, Eva-Maria Mandelkow, Yipeng Wang
Tau aggregation is a hallmark of a group of neurodegenerative diseases termed Tauopathies. Reduction of aggregation-prone Tau has emerged as a promising therapeutic approach. Here, we show that an anti-aggregant Tau fragment (F3ΔKPP , residues 258-360) harboring the ΔK280 mutation and two proline substitutions (I277 P & I308 P) in the repeat domain can inhibit aggregation of Tau constructs in vitro, in cultured cells and in vivo in a Caenorhabditis elegans model of Tau aggregation. The Tau fragment reduced Tau-dependent cytotoxicity in a N2a cell model, suppressed the Tau-mediated neuronal dysfunction and ameliorated the defective locomotion in C...
September 8, 2018: Molecular Neurobiology
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