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https://www.readbyqxmd.com/read/28102462/cerebellar-pathways-in-mouse-model-of-purkinje-cell-degeneration-detected-by-high-angular-resolution-diffusion-imaging-tractography
#1
Yuri Kanamaru, Jianxue Li, Natalie Stewart, Richard L Sidman, Emi Takahashi
Cerebellar MR imaging has several challenging aspects, due to the fine, repetitive layered structure of cortical folia with underlying axonal pathways. In this MR study, we imaged with high-angular resolution diffusion imaging (HARDI) abnormal cerebellar cortical structure (gray matter) and myelinated axonal pathways (white matter) of a mouse spontaneous mutation, Purkinje cell degeneration (pcd), in which almost all Purkinje neurons degenerate, mainly between postnatal days 20 and 35. Mouse brains at postnatal day 20 (P20) and at 8 months were scanned, and known or expected abnormalities, such as reduction of the white matter volume, disorganized pathways likely linked to parallel fibers, mossy fibers, and other fibers running from/to the cerebellar cortex were observed in mutant mice...
January 19, 2017: Cerebellum
https://www.readbyqxmd.com/read/28101715/cortex-and-amygdala-dependent-learning-and-nicotinic-acetylcholine-receptor-gene-expression-is-severely-impaired-in-mice-orally-treated-with-alcl3
#2
Syeda Mehpara Farhat, Aamra Mahboob, Touqeer Ahmed
Recent industrialization has increased human exposure to bio-available aluminum (Al). If more Al enters the brain than leaves, Al concentration will rise in the brain leading to neurodegenerative disorders. The aim of the present study was to determine Al concentration, neurodegeneration, and nicotinic acetylcholine receptor (nAChR) gene expression in the cortex and amygdala after oral ingestion of Al salt. The effect of Al on cortex- and amygdala-dependent learning and memory functions was also assessed. Mice were given AlCl3 (250 mg/kg) in drinking water for 42 days...
January 18, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28100787/polymorphic-variants-of-human-protein-l-isoaspartyl-methyltransferase-affect-catalytic-activity-aggregation-and-thermal-stability-implications-for-the-etiology-of-neurological-disorders-and-cognitive-aging
#3
Charity Juang, Baihe Chen, Jean-Louis Bru, Katherine Nguyen, Eric Huynh, Mahsa Momen, Jeungjin Kim, Dana W Aswad
Protein L-isoaspartyl methyltransferase (PIMT/PCMT1), a product of the human pcmt1 gene, catalyzes repair of abnormal L-isoaspartyl linkages in age-damaged proteins. Pcmt1 knockout mice exhibit a profound neuropathology and die 30-60 days postnatal from an epileptic seizure. Here we express 15 reported variants of human PIMT and characterize them with regard to their enzymatic activity, thermal stability, and propensity to aggregation. One mutation, R36C, renders PIMT completely inactive, while two others, A7P and I58V, exhibit activity that is 80-100% higher than wild type...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100738/mir-142-3p-is-a-key-regulator-of-il-1%C3%AE-dependent-synaptopathy-in-neuroinflammation
#4
Georgia Mandolesi, Francesca De Vito, Alessandra Musella, Antonietta Gentile, Silvia Bullitta, Diego Fresegna, Helena Sepman, Claudio Di Sanza, Nabila Haji, Francesco Mori, Fabio Buttari, Emerald Perlas, Maria Teresa Ciotti, Eran Hornstein, Irene Bozzoni, Carlo Presutti, Diego Centonze
: MicroRNAs (miRNA) play an important role in post-transcriptional gene regulation of several physiological and pathological processes. In multiple sclerosis (MS), a chronic inflammatory and degenerative disease of the CNS, and in its mouse model, the experimental autoimmune encephalomyelitis (EAE), miRNA dysregulation has been mainly related to immune system dysfunction and white matter (WM) pathology. However, little is known about their role in gray matter pathology. Here, we explored miRNA involvement in the inflammation-driven alterations of synaptic structure and function, collectively known as synaptopathy, a neuropathological process contributing to excitotoxic neurodegeneration in MS/EAE...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28100252/a-cognitive-electrophysiological-signature-differentiates-amnestic-mild-cognitive-impairment-from-normal-aging
#5
Juan Li, Lucas S Broster, Gregory A Jicha, Nancy B Munro, Frederick A Schmitt, Erin Abner, Richard Kryscio, Charles D Smith, Yang Jiang
BACKGROUND: Noninvasive and effective biomarkers for early detection of amnestic mild cognitive impairment (aMCI) before measurable changes in behavioral performance remain scarce. Cognitive event-related potentials (ERPs) measure synchronized synaptic neural activity associated with a cognitive event. Loss of synapses is a hallmark of the neuropathology of early Alzheimer's disease (AD). In the present study, we tested the hypothesis that ERP responses during working memory retrieval discriminate aMCI from cognitively normal controls (NC) matched in age and education...
January 19, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28099189/productive-infection-of-human-neural-progenitor-cells-by-r5-tropic-hiv-1-opiate-co-exposure-heightens-infectivity-and-functional-vulnerability
#6
Joyce M Balinang, Ruturaj R Masvekar, Kurt F Hauser, Pamela E Knapp
OBJECTIVE: Human immunodeficiency virus type-1 (HIV-1) causes a spectrum of CNS complications; many are worsened by opiate co-exposure. Human neural progenitor cells (hNPCs) give rise to all CNS neurons and macroglia. We tested the hypothesis that hNPC maturation and fate are altered by HIV and opiates, contributing to HIV-1-related neuropathology. Since reports that hNPCs are infectable remain controversial, we rigorously examined hNPC infection and ability to propagate infection, and determined whether HIV effects on hNPC function required infection...
January 17, 2017: AIDS
https://www.readbyqxmd.com/read/28098781/distinct-neurotoxicity-profile-of-listeriolysin-o-from-listeria-monocytogenes
#7
Jana Maurer, Sabrina Hupp, Carolin Bischoff, Christina Foertsch, Timothy J Mitchell, Trinad Chakraborty, Asparouh I Iliev
Cholesterol-dependent cytolysins (CDCs) are protein toxins that originate from Gram-positive bacteria and contribute substantially to their pathogenicity. CDCs bind membrane cholesterol and build prepores and lytic pores. Some effects of the toxins are observed in non-lytic concentrations. Two pathogens, Streptococcus pneumoniae and Listeria monocytogenes, cause fatal bacterial meningitis, and both produce toxins of the CDC family-pneumolysin and listeriolysin O, respectively. It has been demonstrated that pneumolysin produces dendritic varicosities (dendrite swellings) and dendritic spine collapse in the mouse neocortex, followed by synaptic loss and astrocyte cell shape remodeling without elevated cell death...
January 13, 2017: Toxins
https://www.readbyqxmd.com/read/28098193/non-pathogenic-tissue-resident-cd8-t-cells-uniquely-accumulate-in-the-brains-of-lupus-prone-mice
#8
Peter A Morawski, Chen-Feng Qi, Silvia Bolland
Severe lupus often includes psychiatric and neurological sequelae, although the cellular contributors to CNS disease remain poorly defined. Using intravascular staining to discriminate tissue-localized from blood-borne cells, we find substantial accumulation of CD8(+) T cells relative to other lymphocytes in brain tissue, which correlates with lupus disease and limited neuropathology. This is in contrast to all other affected organs, where infiltrating CD4(+) cells are predominant. Brain-infiltrating CD8(+) T cells represent an activated subset of those found in the periphery, having a resident-memory phenotype (CD69(+)CD122(-)PD1(+)CD44(+)CD62L(-)) and expressing adhesion molecules (VLA-4(+)LFA-1(+)) complementary to activated brain endothelium...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097492/activation-of-trpm2-and-trpv1-channels-in-dorsal-root-ganglion-by-nadph-oxidase-and-protein-kinase-c-molecular-pathways-a-patch-clamp-study
#9
Mustafa Nazıroğlu
Despite considerable research, the mechanisms of neuropathic pain induced by excessive oxidative stress production and overload calcium ion (Ca(2+)) entry in dorsal root ganglion (DRG) remain substantially unidentified. The transient receptor potential melastatin 2 (TRPM2) and vanilloid 1 (TRPV1) channels are activated with different stimuli including oxidative stress. TRPM2 and TRPV1 have been shown to be involved in induction of neuropathic pain. However, the activation mechanisms of TRPM2 and TRPV1 via NADPH oxidase and protein kinase C (PKC) pathways are poorly understood...
January 17, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28097223/abca7-loss-of-function-variants-expression-and-neurologic-disease-risk
#10
Mariet Allen, Sarah J Lincoln, Morgane Corda, Jens O Watzlawik, Minerva M Carrasquillo, Joseph S Reddy, Jeremy D Burgess, Thuy Nguyen, Kimberly Malphrus, Ronald C Petersen, Neill R Graff-Radford, Dennis W Dickson, Nilüfer Ertekin-Taner
OBJECTIVE: To investigate and characterize putative "loss-of-function" (LOF) adenosine triphosphate-binding cassette, subfamily A member 7 (ABCA7) mutations reported to associate with Alzheimer disease (AD) risk. METHODS: We genotyped 6 previously reported ABCA7 putative LOF variants in 1,465 participants with AD, 381 participants with other neuropathologies (non-AD), and 1,043 controls and assessed the overall mutational burden for association with different diagnosis groups...
February 2017: Neurology. Genetics
https://www.readbyqxmd.com/read/28097206/-18-f-av-1451-pet-in-behavioral-variant-frontotemporal-dementia-due-to-mapt-mutation
#11
W Richard Bevan Jones, Thomas E Cope, Luca Passamonti, Tim D Fryer, Young T Hong, Franklin Aigbirhio, Jillian J Kril, Shelley L Forrest, Kieren Allinson, Jonathan P Coles, P Simon Jones, Maria G Spillantini, John R Hodges, John T O'Brien, James B Rowe
The validation of tau radioligands could improve the diagnosis of frontotemporal lobar degeneration and the assessment of disease-modifying therapies. Here, we demonstrate that binding of the tau radioligand [(18)F]AV-1451 was significantly abnormal in both magnitude and distribution in a patient with familial frontotemporal dementia due to a MAPT 10 + 16C>T gene mutation, recapitulating the pattern of neuropathology seen in her father. Given the genetic diagnosis and the non-Alzheimer's pathology, these findings suggest that [(18)F]AV-1451 might be a useful biomarker in primary tauopathies...
December 2016: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28096357/prion-replication-without-host-adaptation-during-interspecies-transmissions
#12
Jifeng Bian, Vadim Khaychuk, Rachel C Angers, Natalia Fernández-Borges, Enric Vidal, Crystal Meyerett-Reid, Sehun Kim, Carla L Calvi, Jason C Bartz, Edward A Hoover, Umberto Agrimi, Jürgen A Richt, Joaquín Castilla, Glenn C Telling
Adaptation of prions to new species is thought to reflect the capacity of the host-encoded cellular form of the prion protein (PrP(C)) to selectively propagate optimized prion conformations from larger ensembles generated in the species of origin. Here we describe an alternate replicative process, termed nonadaptive prion amplification (NAPA), in which dominant conformers bypass this requirement during particular interspecies transmissions. To model susceptibility of horses to prions, we produced transgenic (Tg) mice expressing cognate PrP(C) Although disease transmission to only a subset of infected TgEq indicated a significant barrier to EqPrP(C) conversion, the resulting horse prions unexpectedly failed to cause disease upon further passage to TgEq...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096244/experimental-models-of-inherited-prp-prion-diseases
#13
Joel C Watts, Stanley B Prusiner
The inherited prion protein (PrP) prion disorders, which include familial Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease, and fatal familial insomnia, constitute ∼10%-15% of all PrP prion disease cases in humans. Attempts to generate animal models of these disorders using transgenic mice expressing mutant PrP have produced variable results. Although many lines of mice develop spontaneous signs of neurological illness with accompanying prion disease-specific neuropathological changes, others do not...
January 17, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28096243/fused-in-sarcoma-neuropathology-in-neurodegenerative-disease
#14
Ian R A Mackenzie, Manuela Neumann
Abnormal intracellular accumulation of the fused in sarcoma (FUS) protein is the characteristic pathological feature of cases of familial amyotrophic lateral sclerosis (ALS) caused by FUS mutations (ALS-FUS) and several uncommon disorders that may present with sporadic frontotemporal dementia (FTLD-FUS). Although these findings provide further support for the concept that ALS and FTD are closely related clinical syndromes with an overlapping molecular basis, important differences in the pathological features and results from experimental models indicate that ALS-FUS and FTLD-FUS have distinct pathogenic mechanisms...
January 17, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28093855/typical-and-atypical-appearance-of-early-onset-alzheimer-s-disease-a-clinical-neuroimaging-and-neuropathological-study-symposium-fundamentals-learned-from-diversity-among-typical-and-atypical-appearances
#15
Shinobu Kawakatsu 川勝 忍, Ryota Kobayashi, Hiroshi Hayashi
The International Working Group (IWG) has classified Alzheimer's disease (AD) as two different types, the typical form and the atypical form, but clinicopathological studies of atypical AD are limited. Because atypical AD cases usually present with early-onset dementia, we investigated 12 patients with early-onset AD, including two patients with typical AD and 10 patients with atypical AD. Of these patients, six had the posterior variant, three had the frontal variant and one had the logopenic variant mixed with semantic dementia...
January 17, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28093610/the-new-who-2016-classification-of-brain-tumors-what-neurosurgeons-need-to-know
#16
REVIEW
Rouzbeh Banan, Christian Hartmann
BACKGROUND: The understanding of molecular alterations of tumors has severely changed the concept of classification in all fields of pathology. The availability of high-throughput technologies such as next-generation sequencing allows for a much more precise definition of tumor entities. Also in the field of brain tumors a dramatic increase of knowledge has occurred over the last years partially calling into question the purely morphologically based concepts that were used as exclusive defining criteria in the WHO 2007 classification...
January 17, 2017: Acta Neurochirurgica
https://www.readbyqxmd.com/read/28093567/beta-amyloid-sequelae-in-the-eye-a-critical-review-on-its-diagnostic-significance-and-clinical-relevance-in-alzheimer-s-disease
#17
REVIEW
T M Shah, S M Gupta, P Chatterjee, M Campbell, R N Martins
Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disorder. There is no test for its definitive diagnosis in routine clinical practice. Although phase III clinical trials have failed, only symptomatic treatment is currently available; a possible reason for these failed trials is that intervention commenced at an advanced stage of the disease. The hallmarks of an AD brain include plaques comprising of extracellular beta-amyloid (Aβ) protein aggregates and intracellular hyperphosphorylated neurofibrillary tangles of tau...
January 17, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28093554/tumour-necrosis-factor-mediated-homeostatic-synaptic-plasticity-in-behavioural-models-testing-a-role-in-maternal-immune-activation
#18
Sarah C Konefal, David Stellwagen
The proinflammatory cytokine tumour necrosis factor-alpha (TNFα) has long been characterized for its role in the innate immune system, but more recently has been found to have a distinct role in the nervous system that does not overlap with other proinflammatory cytokines. Through regulation of neuronal glutamate and GABA receptor trafficking, TNF mediates a homeostatic form of synaptic plasticity, but plays no direct role in Hebbian forms of plasticity. As yet, there is no evidence to suggest that this adaptive plasticity plays a significant role in normal development, but it does maintain neuronal circuit function in the face of several types of disruption...
March 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28093254/risperidone-ameliorated-a%C3%AE-1-42-induced-cognitive-and-hippocampal-synaptic-impairments-in-mice
#19
Lingzhi Wu, Xiaowen Feng, Tingting Li, Baojuan Sun, Muhammad Zahid Khan, Ling He
Alzheimer's disease (AD) is a complex neurodegenerative disorder with cognitive impairment and major neuropathologic hallmark of amyloid-beta (Aβ) peptides. Risperidone, an atypical antipsychotic, can improve concentration and cognitive deficit in schizophrenia patients. In this study, behavior tests including Morris Water Maze test, Step-through passive avoidance test, Open Field test, Step-Down test, Hole-Board test and Novel object recognition test were preformed to examine the effect of Risperidone on Aβ1-42-induced cognitive dysfunction in both long-term and short-term memory...
January 13, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28092022/relevance-of-neuroimaging-for-neurocognitive-and-behavioral-outcome-after-pediatric-traumatic-brain-injury
#20
Marsh Königs, Petra Jw Pouwels, L W Ernest van Heurn, Roel Bakx, R Jeroen Vermeulen, J Carel Goslings, Bwee Tien Poll-The, Marleen van der Wees, Coriene E Catsman-Berrevoets, Jaap Oosterlaan
This study aims to (1) investigate the neuropathology of mild to severe pediatric TBI and (2) elucidate the predictive value of conventional and innovative neuroimaging for functional outcome. Children aged 8-14 years with trauma control (TC) injury (n = 27) were compared to children with mild TBI and risk factors for complicated TBI (mild(RF+), n = 20) or moderate/severe TBI (n = 17) at 2.8 years post-injury. Neuroimaging measures included: acute computed tomography (CT), volumetric analysis on post-acute conventional T1-weighted magnetic resonance imaging (MRI) and post-acute diffusion tensor imaging (DTI, analyzed using tract-based spatial statistics and voxel-wise regression)...
January 14, 2017: Brain Imaging and Behavior
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