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https://www.readbyqxmd.com/read/29161341/distinct-spatiotemporal-accumulation-of-n-truncated-and-full-length-amyloid-%C3%AE-42-in-alzheimer-s-disease
#1
Mitsuru Shinohara, Shunsuke Koga, Takuya Konno, Jeremy Nix, Motoko Shinohara, Naoya Aoki, Pritam Das, Joseph E Parisi, Ronald C Petersen, Terrone L Rosenberry, Dennis W Dickson, Guojun Bu
Accumulation of amyloid-β peptides is a dominant feature in the pathogenesis of Alzheimer's disease; however, it is not clear how individual amyloid-β species accumulate and affect other neuropathological and clinical features in the disease. Thus, we compared the accumulation of N-terminally truncated amyloid-β and full-length amyloid-β, depending on disease stage as well as brain area, and determined how these amyloid-β species respectively correlate with clinicopathological features of Alzheimer's disease...
November 17, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29158604/antiviral-cd8-t-cells-induce-zika-virus-associated-paralysis-in-mice
#2
Kellie A Jurado, Laura J Yockey, Patrick W Wong, Sarah Lee, Anita J Huttner, Akiko Iwasaki
Zika virus (ZIKV) is an emerging, mosquito-borne RNA virus. The rapid spread of ZIKV within the Americas has unveiled microcephaly (1) and Guillain-Barré syndrome (2,3) as ZIKV-associated neurological complications. Recent reports have also indicated other neurological manifestations to be associated with ZIKV, including myelitis (4) , meningoencephalitis (5) and fatal encephalitis (6) . Here, we investigate the neuropathogenesis of ZIKV infection in type I interferon receptor IFNAR knockout (Ifnar1 (-/-) ) mice, an infection model that exhibits high viral burden within the central nervous system...
November 20, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/29158185/cdk5-mediated-phosphorylation-of-sirt2-contributes-to-depressive-like-behavior-induced-by-social-defeat-stress
#3
Zheng Zhang, Pei Zhang, Guang-Jian Qi, Feng-Juan Jiao, Qing-Zhi Wang, Jian-Guo Yan, Feng He, Qian Zhang, Ze-Xi Lv, Xiang Peng, Hong-Wei Cai, Xiaoqian Chen, Ning Sun, Bo Tian
Major depressive disorder (MDD) is a common, severe and recurrent psychiatric disorder worldwide; however, the underlying neuropathological mechanisms remain elusive. Histone deacetylases (HDACs) appear to play an essential role in depression. As the class III HDACs, Sirt1 and Sirt2 have attracted the most interest in the nervous system. Indeed, chronic stress decreased Sirt1 activity and down-regulated Sirt1 gene expression in MDD. Nevertheless, there is a paucity of literature on the role of Sirt2. To study the role of Sirt2 we established a MDD mouse model in wild type and Sirt2 knockout C57BL/6 mice using social defeat stress (SDS)...
November 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29157505/sports-related-concussion-acute-management-and-chronic-postconcussive-issues
#4
REVIEW
Navid Mahooti
Sports-related concussion (SRC) is a common problem in youth sports. Concussion may occur after a forceful hit to the body or head, resulting in transient neuropathological changes that spontaneously resolve with relative rest and activity modification in most patients. Most SRCs are effectively managed by primary care physicians and sports medicine specialists. In some cases, symptoms may persist and the child and adolescent psychiatrist may be consulted. This article reviews important background information regarding SRC and highlights a variety of pharmacologic and nonpharmacologic treatment options that consultant psychiatrists should know...
January 2018: Child and Adolescent Psychiatric Clinics of North America
https://www.readbyqxmd.com/read/29155947/dementia-after-moderate-severe-traumatic-brain-injury-coexistence-of-multiple-proteinopathies
#5
Kimbra Kenney, Diego Iacono, Brian L Edlow, Douglas I Katz, Ramon Diaz-Arrastia, Kristen Dams-O'Connor, Daniel H Daneshvar, Allison Stevens, Allison L Moreau, Lee S Tirrell, Ani Varjabedian, Anastasia Yendiki, Andre van der Kouwe, Azma Mareyam, Jennifer A McNab, Wayne A Gordon, Bruce Fischl, Ann C McKee, Daniel P Perl
We report the clinical, neuroimaging, and neuropathologic characteristics of 2 patients who developed early onset dementia after a moderate-severe traumatic brain injury (TBI). Neuropathological evaluation revealed abundant β-amyloid neuritic and cored plaques, diffuse β-amyloid plaques, and frequent hyperphosphorylated-tau neurofibrillary tangles (NFT) involving much of the cortex, including insula and mammillary bodies in both cases. Case 1 additionally showed NFTs in both the superficial and deep cortical layers, occasional perivascular and depth-of-sulci NFTs, and parietal white matter rarefaction, which corresponded with decreased parietal fiber tracts observed on ex vivo MRI...
November 16, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29155769/a-simple-approach-to-induce-experimental-autoimmune-neuritis-in-c57bl-6-mice-for-functional-and-neuropathological-assessments
#6
David G Gonsalvez, Jessica L Fletcher, Sang Won Yoo, Rhiannon J Wood, Simon S Murray, Junhua Xiao
Experimental autoimmune neuritis (EAN) is a well-appreciated experimental model of autoimmune peripheral demyelinating diseases. EAN disease is induced by immunizing mice with neurogenic peptides to direct an inflammatory attack toward components of the peripheral nervous system (PNS). Recent advances have enabled the induction of EAN in the relatively resistant C57BL/6 mouse line using myelin protein zero (P0)106-125 or P0180-199 peptides delivered in adjuvant combined with the injection of pertussis toxin...
November 9, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155349/endogenous-sulfur-dioxide-regulates-hippocampal-neuron-apoptosis-in-developing-epileptic-rats-and-is-associated-with-the-perk-signaling-pathway
#7
Manman Niu, Ying Han, Qinrui Li, Jing Zhang
Epilepsy is among the most common neurological diseases in children. Recurrent seizures can result in hippocampal damage and seriously impair learning and memory functions in children. However, the mechanisms underlying epilepsy-related brain injury are unclear. Neuronal apoptosis is among the most common neuropathological manifestations of brain injury. Endogenous sulfur dioxide (SO2) has been shown to be involved in seizures and related neuron apoptosis. However, the role of endogenous SO2 in epilepsy remains unclear...
November 16, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29154751/the-etiology-of-spontaneous-intracerebralhemorrhage-insights-from-a-neuropathological-series
#8
Luis Ruano, Mariana Branco, Raquel Samões, Ricardo Taipa, Manuel Melo Pires
The etiology of intracerebral hemorrhage (ICH) is frequently undetermined. We aimed to assess the impact of the neuropathological study on the etiologic diagnosis of ICH. Patients with ICH admitted to a tertiary hospital in the last 14 years were identified, and histological samples of surgically-drained ICH were retrieved. Blinded from neuropathological results, a clinical etiology was hypothesized. Pathological samples were reviewed, and immunohistochemistry study for β-amyloid was performed in all the cases where structural abnormalities were not identified...
November 20, 2017: Clinical Neuropathology
https://www.readbyqxmd.com/read/29154280/sisyphus-in-neverland
#9
Isidro Ferrer
The study of life and living organisms and the way in which these interact and organize to form social communities have been central to my career. I have been fascinated by biology, neurology, and neuropathology, but also by history, sociology, and art. Certain current historical, political, and social events, some occurring proximally but others affecting people in apparently distant places, have had an impact on me. Epicurus, Seneca, and Camus shared their philosophical positions which I learned from. Many scientists from various disciplines have been exciting sources of knowledge as well...
November 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29151169/parkinson-s-disease-experimental-models-and-reality
#10
REVIEW
Peizhou Jiang, Dennis W Dickson
Parkinson's disease (PD) is a chronic, progressive movement disorder of adults and the second most common neurodegenerative disease after Alzheimer's disease. Neuropathologic diagnosis of PD requires moderate-to-marked neuronal loss in the ventrolateral substantia nigra pars compacta and α-synuclein (αS) Lewy body pathology. Nigrostriatal dopaminergic neurodegeneration correlates with the Parkinsonian motor features, but involvement of other peripheral and central nervous system regions leads to a wide range of non-motor features...
November 18, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/29150979/anterior-thalamic-nuclei-lesions-have-a-greater-impact-than-mammillothalamic-tract-lesions-on-the-extended-hippocampal-system
#11
Brook A L Perry, Stephanie A Mercer, Sophie C Barnett, Jungah Lee, John C Dalrymple-Alford
The anterior thalamic nuclei (ATN), mammillary bodies and their interconnecting fiber tract, the mammillothalamic tract (MTT), are important components of an extended hippocampal circuit for episodic memory. In humans, damage to the MTT or ATN in many disorders is associated with severe anterograde amnesia and it is assumed that their influence on memory is functionally equivalent. The relative influence of these two structures on memory has not, however, been assessed explicitly. Here, a direct comparison found that only ATN lesions impaired spatial reference memory in rats...
November 18, 2017: Hippocampus
https://www.readbyqxmd.com/read/29150951/inflammasome-its-role-in-traumatic-brain-and-spinal-cord-injury
#12
REVIEW
Keywan Mortezaee, Neda Khanlarkhani, Cordian Beyer, Adib Zendedel
Traumatic brain injury (TBI) and spinal cord injury (SCI) are pathological events that lead to neuropathological conditions which have in consequence the initiation of pro-inflammatory cytokine production. Neuroinflammation plays a key role in the secondary phase of both TBI and SCI after initial cell death. Activation of cytoplasmic inflammasome complexes is regarded as the essential step of neuroinflammation and a key trigger for neuronal death called pyroptosis. Inflammasome complexes are involved in activation of caspase-1 which catalyzes the cleavage of pro-interleukins into their active forms (including interleukin-18 (IL-18) and IL-1β)...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150892/expanding-the-neurodevelopmental-phenotype-of-pura-syndrome
#13
Bo Hoon Lee, Margot R F Reijnders, Oluwatobi Abubakare, Emily Tuttle, Brynn Lape, Kelly Q Minks, Christopher Stodgell, Loisa Bennetto, Jennifer Kwon, Chin-To Fong, Karen W Gripp, Eric D Marsh, Wendy E Smith, Ahm M Huq, Stephanie A Coury, Wen-Hann Tan, Orestes Solis, Rupal I Mehta, Richard J Leventer, Diana Baralle, David Hunt, Alex R Paciorkowski
PURA syndrome is a recently described developmental encephalopathy presenting with neonatal hypotonia, feeding difficulties, global developmental delay, severe intellectual disability, and frequent apnea and epilepsy. We describe 18 new individuals with heterozygous sequence variations in PURA. A neuromotor disorder starting with neonatal hyptonia, but ultimately allowing delayed progression to walking, was present in nearly all individuals. Congenital apnea was present in 56% during infancy, but all cases in this cohort resolved during the first year of life...
November 17, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29150269/potential-role-of-the-virchow-robin-space-in-the-pathogenesis-of-bacterial-meningitis
#14
Patrick Chan, Denis J Meerdink, James A Uchizono
Meningitis is an infectious disease commonly arising from a bacterial etiology. The rapid progression of morbidity and mortality due to bacterial meningitis requires critical and imminent time-dependent clinical intervention. Although it is unambiguously clear that bacteria must infiltrate the cerebrospinal fluid, the sequence of events in the pathogenesis of bacterial meningitis has not been fully elucidated. Most reviews of the pathogenesis of bacterial meningitis do not specify the anatomical location of bacteria following BBB traversal...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29149899/selective-depletion-of-microglial-progranulin-in-mice-is-not-sufficient-to-cause-neuronal-ceroid-lipofuscinosis-or-neuroinflammation
#15
Terri L Petkau, Natalia Kosior, Kathleen de Asis, Colúm Connolly, Blair R Leavitt
BACKGROUND: Progranulin deficiency due to heterozygous null mutations in the GRN gene are a common cause of familial frontotemporal lobar degeneration (FTLD), while homozygous loss-of-function GRN mutations are thought to be a rare cause of neuronal ceroid lipofuscinosis (NCL). Aged progranulin-knockout (Grn-null) mice display highly exaggerated lipofuscinosis, microgliosis, and astrogliosis, as well as mild cell loss in specific brain regions. In the brain, progranulin is predominantly expressed in neurons and microglia, and previously, we demonstrated that neuronal-specific depletion of progranulin does not recapitulate the neuropathological phenotype of Grn-null mice...
November 17, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29146478/diacylglycerols-as-biomarkers-of-sustained-immune-activation-in-proteinopathies-associated-with-dementia
#16
REVIEW
Paul L Wood, John E Cebak, Randall L Woltjer
Cognitive decline is a devastating clinical condition, heavily correlated with age progression. In the cases of Alzheimer's disease, Parkinson's disease, and Lewy body disease, the common neuropathologies are proteinopathies and neuroinflammation. Herein, we review current lipidomics findings and conclude that brain and circulating diacylglycerols represent biomarkers of this ongoing sustained immune response, presumably involving microglia. We further hypothesize that a logical next step will be to evaluate biomarkers of immune activation in a cohort of patients with Mild Cognitive Impairment (MCI) and subsequently attempt to provide therapeutic intervention with anti-inflammatory therapy in MCI patients with immune activation...
November 13, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29146111/microrna-expression-patterns-in-human-anterior-cingulate-and-motor-cortex-a-study-of-dementia-with-lewy-bodies-cases-and-controls
#17
Peter T Nelson, Wang-Xia Wang, Sarah A Janse, Katherine L Thompson
OVERVIEW: MicroRNAs (miRNAs) have been implicated in neurodegenerative diseases including Parkinson's disease and Alzheimer's disease (AD). Here, we evaluated the expression of miRNAs in anterior cingulate (AC; Brodmann area [BA] 24) and primary motor (MO; BA 4) cortical tissue from aged human brains in the University of Kentucky AD Center autopsy cohort, with a focus on dementia with Lewy bodies (DLB). METHODS: RNA was isolated from gray matter of brain samples with pathology-defined DLB, AD, AD+DLB, and low-pathology controls, with n=52 cases initially included (n=23 with DLB), all with low (<4hrs) postmortem intervals...
November 13, 2017: Brain Research
https://www.readbyqxmd.com/read/29145658/characterization-of-detergent-insoluble-proteome-in-chronic-traumatic-encephalopathy
#18
Jonathan D Cherry, Ahmad Zeineddin, Eric B Dammer, James A Webster, Duc Duong, Nicholas T Seyfried, Allan I Levey, Victor E Alvarez, Bertrand R Huber, Thor D Stein, Patrick T Kiernan, Ann C McKee, James J Lah, Chadwick M Hales
Quantitative proteomics of postmortem human brain can identify dysfunctional proteins that contribute to neurodegenerative disorders like Alzheimer disease (AD) and frontotemporal dementia. Similar studies in chronic traumatic encephalopathy (CTE) are limited, therefore we hypothesized that proteomic sequencing of CTE frontal cortex brain homogenates from varying CTE pathologic stages may provide important new insights into this disorder. Quantitative proteomics of control, CTE and AD brains was performed to characterize differentially expressed proteins, and we identified over 4000 proteins in CTE brains, including significant enrichment of the microtubule associated protein tau...
November 14, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29143559/k-cl-co-transporter-2-kcc2-a-membrane-trafficking-perspective
#19
Bor Luen Tang
K(+)-Cl(-) co-transporter 2 (KCC2/SLC12A5) is a neuronal specific cation chloride co-transporter which is active under isotonic conditions, and thus a key regulator of intracellular Cl(-) levels. It also has an ion transporter-independent structural role in modulating the maturation and regulation of excitatory glutamatergic synapses. KCC2 levels are developmentally regulated, and a postnatal upregulation of KCC2 generates a low intracellular chloride concentration that allows the neurotransmitters γ-aminobutyric acid (GABA) and glycine to exert inhibitory neurotransmission through its Cl(-) permeating channel...
November 16, 2017: Molecular Membrane Biology
https://www.readbyqxmd.com/read/29142232/tdp-43-misexpression-causes-defects-in-dendritic-growth
#20
Josiah J Herzog, Mugdha Deshpande, Leah Shapiro, Avital A Rodal, Suzanne Paradis
Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) share overlapping genetic causes and disease symptoms, and are linked neuropathologically by the RNA binding protein TDP-43 (TAR DNA binding protein-43 kDa). TDP-43 regulates RNA metabolism, trafficking, and localization of thousands of target genes. However, the cellular and molecular mechanisms by which dysfunction of TDP-43 contributes to disease pathogenesis and progression remain unclear. Severe changes in the structure of neuronal dendritic arbors disrupt proper circuit connectivity, which in turn could contribute to neurodegenerative disease...
November 15, 2017: Scientific Reports
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