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[PMID]: 26704708
[Au] Autor:Kim Y; Choi H; Lee W; Park H; Kam TI; Hong SH; Nah J; Jung S; Shin B; Lee H; Choi TY; Choo H; Kim KK; Choi SY; Kayed R; Jung YK
[Ad] Address:Global Research Laboratory, School of Biological Sciences, Seoul National University, Seoul 151-747, Republic of Korea....
[Ti] Title:Caspase-cleaved tau exhibits rapid memory impairment associated with tau oligomers in a transgenic mouse model.
[So] Source:Neurobiol Dis;87:19-28, 2016 Mar.
[Is] ISSN:1095-953X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:In neurodegenerative diseases like AD, tau forms neurofibrillary tangles, composed of tau protein. In the AD brain, activated caspases cleave tau at the 421th Asp, generating a caspase-cleaved form of tau, TauC3. Although TauC3 is known to assemble rapidly into filaments in vitro, a role of TauC3 in vivo remains unclear. Here, we generated a transgenic mouse expressing human TauC3 using a neuron-specific promoter. In this mouse, we found that human TauC3 was expressed in the hippocampus and cortex. Interestingly, TauC3 mice showed drastic learning and spatial memory deficits and reduced synaptic density at a young age (2-3months). Notably, tau oligomers as well as tau aggregates were found in TauC3 mice showing memory deficits. Further, i.p. or i.c.v. injection with methylene blue or Congo red, inhibitors of tau aggregation in vitro, and i.p. injection with rapamycin significantly reduced the amounts of tau oligomers in the hippocampus, rescued spine density, and attenuated memory impairment in TauC3 mice. Together, these results suggest that TauC3 facilitates early memory impairment in transgenic mice accompanied with tau oligomer formation, providing insight into the role of TauC3 in the AD pathogenesis associated with tau oligomers and a useful AD model to test drug candidates.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1601
[Js] Journal subset:IM
[St] Status:In-Data-Review

  2 / 274051 MEDLINE  
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[PMID]: 26655144
[Au] Autor:Yang W; Yan H; Ma Y; Yu T; Guo H; Kuang Y; Ren R; Li J
[Ad] Address:Institute of Tropical Medicine, Third Military Medical University, Gaotanyan Street 30, Chongqing 400038, China....
[Ti] Title:Lower activation-induced T-cell apoptosis is related to the pathological immune response in secondary infection with hetero-serotype dengue virus.
[So] Source:Immunobiology;221(3):432-9, 2016 Mar.
[Is] ISSN:1878-3279
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:The available evidence suggests that dengue virus-specific T lymphocytes and cytokine storm play a pivotal role in the immunopathogenesis of plasma leakage. Investigations are underway to identify the immune profiles associated with increased or decreased risk for severe disease. In this study, CD14+ cells from the peripheral blood mononuclear cells (PBMCs) of patients who recovered from DENV-1 infection were infected with DENV-1 or DENV-2 and co-cultured with memory T cells. We found that secondary infection with DENV-2 suppresses the cell reproductive capacity but forms more cell clones and more functional cells to produce more proinflammatory factors (IFN-γ, TNF-α, IL-6, IL-8, IL-12 and IL-17) and less regulatory cytokines (IL-10, TGF-ß) which results in higher viral replication compared to secondary infection with DENV-1. Memory dengue virus-specific T cells which are induced in a primary dengue virus infection are reactivated by the heterologous serotype of dengue virus and antigen-presenting cells (APCs) during a secondary infection. Dramatically, less apoptosis and more continuous activation of T cells in secondary infection with hetero-serotype DENV were observed. This discovery which has not been reported previously may be the reasonable and vital interpretation for the cytokine storm and severe symptoms observed in secondary infection with DENV. In summary, secondary infection with hetero-serotype DENV elicits the relatively pathological immune response while secondary infection with homologous-serotype DENV induces the relatively protective immune response by activation-induced cell death (AICD) of T cells.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1601
[Js] Journal subset:IM
[St] Status:In-Data-Review

  3 / 274051 MEDLINE  
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[PMID]: 26655143
[Au] Autor:Kim WS; Kim JS; Cha SB; Kim SJ; Kim H; Kwon KW; Han SJ; Choi SY; Shin SJ
[Ad] Address:Department of Microbiology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, South Korea....
[Ti] Title:Mycobacterium tuberculosis PE27 activates dendritic cells and contributes to Th1-polarized memory immune responses during in vivo infection.
[So] Source:Immunobiology;221(3):440-53, 2016 Mar.
[Is] ISSN:1878-3279
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:A gradual understanding of the proline-glutamate (PE) and proline-proline-glutamate (PPE) families, which compromise 10% of the coding regions in the Mycobacterium tuberculosis (Mtb) genome, has uncovered unique roles in host-pathogen interactions. However, the immunological function of PE27 (Rv2769c), the largest PE member, remains unclear. Here, we explored the functional roles and related signaling mechanisms of PE27 in the interaction with dendritic cells (DCs) to shape the T cell response. PE27 phenotypically and functionally induces DC maturation by up-regulating CD80, CD86, MHC class I and MHC class II expression on the DC surface to promote the production of TNF-α, IL-1ß, IL-6, and IL-12p70 but not IL-10. Additionally, we found that PE27-mediated DC activation requires the participation of mitogen-activated protein kinases (MAPKs) and nuclear factor κB (NF-κB) signaling pathways. Interestingly, PE27-treated DCs directed naïve CD4(+) T cells to secrete IFN-γ and activate T-bet but not GATA-3. PE27 also induced IFN-γ-producing memory T cell responses in Mtb-infected mice, indicating that PE27 contributes to Th1-polarization. Taken together, these findings suggest that PE27 possesses Th1-polarizing potential through DC maturation and could be useful in the design of TB vaccines.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1601
[Js] Journal subset:IM
[St] Status:In-Data-Review

  4 / 274051 MEDLINE  
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[PMID]: 26621546
[Au] Autor:Shrivastava P; Watkiss E; van Drunen Littel-van den Hurk S
[Ad] Address:VIDO-InterVac, University of Saskatchewan, 120 Veterinary Road, Saskatoon, Saskatchewan S7N 5E3, Canada.
[Ti] Title:The response of aged mice to primary infection and re-infection with pneumonia virus of mice depends on their genetic background.
[So] Source:Immunobiology;221(3):494-502, 2016 Mar.
[Is] ISSN:1878-3279
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:The pneumonia virus of mice (PVM) model is used to study respiratory syncytial virus (RSV) pathogenesis. The outcome of PVM infection varies in different inbred mouse strains, BALB/c being highly susceptible and C57BL/6 more resistant. As the disease symptoms induced by RSV infection can become more severe as people age, we examined the primary and secondary immune responses to infection with PVM in aged BALB/c and C57BL/6 mice. Based on clinical parameters, aged C57BL/6 mice displayed less severe disease than young adult mice when infected with 3000pfu of PVM-15, while BALB/c mice were equally susceptible at both ages showing significant weight loss and high levels of virus replication. Furthermore, after primary infection the CD4(+) T cell numbers in the lungs were higher in young adult mice, while the CD8(+) T cell numbers were comparable in both age groups and strains. When either C57BL/6 or BALB/c mice were infected with PVM as young adults and then re-infected as aged mice, they were protected from clinical disease, while virus replication was reduced. In contrast to mice with a primary PVM-infection, re-infected mice did not have infiltration of neutrophils or inflammatory mediators in the lung. BALB/c mice had higher virus neutralizing antibody levels in the serum and lung than C57BL/6 mice upon re-infection. Re-infection with PVM led to significant influx of effector CD4(+) T cells into the lungs when compared to aged mice with a primary infection, while this cell population was decreased in the lung draining lymph nodes in both mouse strains. After re-infection the effector CD8(+) T cell population was also decreased in the lung draining lymph nodes in both mouse strain when compared to aged mice after primary infection. However, the central memory CD4(+) and CD8(+) T cells were significantly enhanced in numbers in the lungs and draining lymph nodes of both mouse strains after re-infection, and these numbers were higher for C57BL/6 mice.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1601
[Js] Journal subset:IM
[St] Status:In-Data-Review

  5 / 274051 MEDLINE  
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[PMID]: 26388065
[Au] Autor:Bridges RS
[Ad] Address:Department of Biomedical Sciences, Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA, USA. Electronic address: robert.bridges@tufts.edu.
[Ti] Title:Long-term alterations in neural and endocrine processes induced by motherhood in mammals.
[So] Source:Horm Behav;77:193-203, 2016 Jan.
[Is] ISSN:1095-6867
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:This article is part of a Special Issue "Parental Care". The reproductive experience of pregnancy, lactation and motherhood can significantly remodel the female's biological state, affecting endocrine, neuroendocrine, neural, and immunological processes. The brain, pituitary gland, liver, thymus, and mammary tissue are among the structures that are modified by reproductive experience. The present review that focuses on rodent research, but also includes pertinent studies in sheep and other species, identifies specific changes in these processes brought about by the biological states of pregnancy, parturition, and lactation and how the components of reproductive experience contribute to the remodeling of the maternal brain and organ systems. Findings indicate that prior parity alters key circulating hormone levels and neural receptor gene expression. Moreover, reproductive experience results in modifications in neural processes and glial support. The possible role of pregnancy-induced neurogenesis is considered in the context of neuroplasticity and behavior, and the effects of reproductive experience on maternal memory, i.e. the retention of maternal behavior, together with anxiety and learning are presented. Together, these sets of findings support the concept that the neural and biological state of the adult female is significantly and dramatically altered on a long-term basis by the experiences of parity and motherhood. Remodeling of the maternal brain and other biological systems is posited to help facilitate adaptations to environmental/ecological challenges as the female raises young and ages.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1601
[Js] Journal subset:IM
[St] Status:In-Data-Review

  6 / 274051 MEDLINE  
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[PMID]: 26709104
[Au] Autor:Hodges SL; Gabriel MT; Perry MS
[Ad] Address:Institute of Biomedical Studies, Baylor University, Waco, TX, USA. Electronic address: Samantha_Hodges@baylor.edu.
[Ti] Title:Neuropsychological findings associated with Panayiotopoulos syndrome in three children.
[So] Source:Epilepsy Behav;54:158-62, 2016 Jan.
[Is] ISSN:1525-5069
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Panayiotopoulos syndrome is a common idiopathic benign epilepsy that has a peak age of onset in early childhood. The syndrome is multifocal and shows significant electroencephalogram (EEG) variability, with occipital predominance. Although a benign syndrome often refers to the absence of neurological and neuropsychological deficits, the syndrome has recently been associated with cognitive impairments. Also, despite frequent occipital EEG abnormalities, research regarding the visual functioning of patients is less reported and often contradictory. The purpose of this study was to gain additional knowledge regarding the neurocognitive functioning of patients with Panayiotopoulos syndrome and specifically to address any visual processing deficits associated with the syndrome. Following diagnosis of the syndrome based on typical clinical and electrophysiological criteria, three patients, aged 5, 8, and 10years were referred by epileptologists for neuropsychological evaluation. Neuropsychological findings suggest that the patients had notable impairments on visual memory tasks, especially in comparison with verbal memory. Further, they demonstrated increased difficulty on picture memory suggesting difficulty retaining information from a crowded visual field. Two of the three patients showed weakness in visual processing speed, which may account for weaker retention of complex visual stimuli. Abilities involving attention were normal for all patients, suggesting that inattention is not responsible for these visual deficits. Academically, the patients were weak in numerical operations and spelling, which both rely partially on visual memory and may affect achievement in these areas. Overall, the results suggest that patients with Panayiotopoulos syndrome may have visual processing and visual memory problems that could potentially affect their academic capabilities. Identifying such difficulties may be helpful in creating educational and remedial assistance programs for children with this syndrome, as well as developing appropriate presentation of information to these children in school.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1601
[Js] Journal subset:IM
[St] Status:In-Data-Review

  7 / 274051 MEDLINE  
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[PMID]: 26709103
[Au] Autor:Kowski AB; Weissinger F; Gaus V; Fidzinski P; Losch F; Holtkamp M
[Ad] Address:Epilepsy-Center Berlin-Brandenburg, Department of Neurology, Charité - Universitätsmedizin Berlin, Germany. Electronic address: alexander.kowski@charite.de....
[Ti] Title:Specific adverse effects of antiepileptic drugs - A true-to-life monotherapy study.
[So] Source:Epilepsy Behav;54:150-7, 2016 Jan.
[Is] ISSN:1525-5069
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: In patients taking antiepileptic drugs (AEDs) for epilepsy, adverse effects (AEs) often lead to unfavorable quality of life, impaired adherence, and, eventually, discontinuation of pharmacological treatment. In a true-to-life sample of subjects from our academic epilepsy outpatient clinic, we aimed to identify predictors for overall high AE burden and for specific AEs focusing on patients on monotherapy. METHODS: All patients ≥16years of age with epilepsy for ≥12months were routinely asked to complete the Liverpool Adverse Event Profile (LAEP) just before their appointment. Demographic, epilepsy, and treatment variables were derived from our comprehensive outpatient database. RESULTS: Out of 841 patients, 438 (61% female, mean age: 44.7±17.1years) on monotherapy were included in this study. Levetiracetam (n=151), lamotrigine (n=167), valproic acid (n=73), or controlled-release carbamazepine (n=47) were the most commonly used antiepileptic drugs (AEDs). Independent predictors for general high AE burden (LAEP score≥45) were duration of epilepsy, lack of 12-month seizure freedom, and partial epilepsy, but none of the four individual AEDs. The most frequent LAEP-defined specific AEs were sleepiness, difficulty concentrating, tiredness, and memory problems. The three most frequent independent predictors for each of the 19 AEs were lack of 12-month seizure freedom (13/19 AEs), individual AED (7/19 AEs), and partial epilepsy (6/19 AEs). Levetiracetam was independently associated with anger/aggression, nervousness/agitation, upset stomach, depression, and sleep disturbance; lamotrigine with nervousness/agitation, upset stomach, and difficulty concentrating; and valproic acid with upset stomach and shaky hands. CONCLUSION: Individual AEDs independently predicted some specific AEs, but not overall high AE burden. Our findings may help to characterize patients with epilepsy who are at high risk for specific AEs. Dose reduction or change to another AED may reduce LAEP score and potential nonadherence.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1601
[Js] Journal subset:IM
[St] Status:In-Data-Review

  8 / 274051 MEDLINE  
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[PMID]: 26708060
[Au] Autor:Warburton A; Miyajima F; Shazadi K; Crossley J; Johnson MR; Marson AG; Baker GA; Quinn JP; Sills GJ
[Ad] Address:Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GL, UK....
[Ti] Title:NRSF and BDNF polymorphisms as biomarkers of cognitive dysfunction in adults with newly diagnosed epilepsy.
[So] Source:Epilepsy Behav;54:117-27, 2016 Jan.
[Is] ISSN:1525-5069
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Cognitive dysfunction is a common comorbidity in people with epilepsy, but its causes remain unclear. It may be related to the etiology of the disorder, the consequences of seizures, or the effects of antiepileptic drug treatment. Genetics may also play a contributory role. We investigated the influence of variants in the genes encoding neuron-restrictive silencer factor (NRSF) and brain-derived neurotrophic factor (BDNF), proteins previously associated with cognition and epilepsy, on cognitive function in people with newly diagnosed epilepsy. A total of 82 patients who had previously undergone detailed neuropsychological assessment were genotyped for single nucleotide polymorphisms (SNPs) across the NRSF and BDNF genes. Putatively functional SNPs were included in a genetic association analysis with specific cognitive domains, including memory, psychomotor speed, and information processing. Cross-sectional and longitudinal designs were used to explore genetic influences on baseline cognition at diagnosis and change from baseline over the first year since diagnosis, respectively. We found a statistically significant association between genotypic variation and memory function at both baseline (NRSF: rs1105434, rs2227902 and BDNF: rs1491850, rs2030324, rs11030094) and in our longitudinal analysis (NRSF: rs2227902 and BDNF: rs12273363). Psychomotor speed was also associated with genotype (NRSF rs3796529) in the longitudinal assessment. In line with our previous work on general cognitive function in the healthy aging population, we observed an additive interaction between risk alleles for the NRSF rs2227902 (G) and BDNF rs6265 (A) polymorphisms which was again consistent with a significantly greater decline in delayed recall over the first year since diagnosis. These findings support a role for the NRSF-BDNF pathway in the modulation of cognitive function in patients with newly diagnosed epilepsy.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1601
[Js] Journal subset:IM
[St] Status:In-Data-Review

  9 / 274051 MEDLINE  
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[PMID]: 26687293
[Au] Autor:Valente KD; Rzezak P; Moschetta SP; de Vincentiis S; Coan AC; Guerreiro CA
[Ad] Address:Laboratory of Clinical Neurophysiology, Institute of Psychiatry, University of São Paulo Medical School (IPq-HC-FMUSP), Brazil; Psychology & Neuropsychology Unit, IPq-HC-FMUSP, Brazil; LIM 21 - Laboratory of Neuroimaging in Neuropsychiatric Disorders, Institute and Department of Psychiatry, Univ...
[Ti] Title:Delineating behavioral and cognitive phenotypes in juvenile myoclonic epilepsy: Are we missing the forest for the trees?
[So] Source:Epilepsy Behav;54:95-9, 2016 Jan.
[Is] ISSN:1525-5069
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:INTRODUCTION: Patients with juvenile myoclonic epilepsy (JME) have executive dysfunction and impulsive traits. There are lines of evidence that JME is a heterogeneous epilepsy syndrome considering outcome. In this study, we aimed to analyze this heterogeneity beyond seizure control. The objective was to identify whether the pattern of cognitive dysfunction and impulse control is also heterogeneous, in an attempt to establish possible differences in patients with easy- and hard-to-control epilepsies. METHODS: Essentially, 57 patients with JME were compared with 44 controls. Patients and controls were assessed with a neuropsychological battery for executive, attention, and memory functions. The expression of impulsive traits was evaluated with the Temperament and Character Inventory - novelty seeking domain. Then, patients were categorized according to seizure control as having easy- and hard-to-control JME. RESULTS: Patients with hard-to-control JME showed worse performance in 12 out of 25 neuropsychological tests than those with easy-to-control JME. Patients with hard-to-control JME also demonstrated significantly higher scores in novelty seeking - subfactor impulsiveness (p=0.002). SIGNIFICANCE: Our study demonstrated the existence of distinct or more severe cognitive and psychiatric profiles in a subset of patients with JME. Patients with treatment-refractory seizures seem to present a broader impairment related to both cognitive deficits and impulsive traits. These findings suggest that patients with JME are not equally compromised by executive and memory deficits or dysfunction, neither by their impulsive traits. Thus, there is a need for a better characterization of patients with JME to include diverse phenotypes since our results suggest a possible existence of distinct groups of patients with JME.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1601
[Js] Journal subset:IM
[St] Status:In-Data-Review

  10 / 274051 MEDLINE  
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[PMID]: 26667848
[Au] Autor:Filippini M; Ardu E; Stefanelli S; Boni A; Gobbi G; Benso F
[Ad] Address:Child Neurology Unit, IRCCS Istituto delle Scienze Neurologiche, via Altura 3, 40139 Bologna, Italy. Electronic address: melissa.filippini@libero.it....
[Ti] Title:Neuropsychological profile in new-onset benign epilepsy with centrotemporal spikes (BECTS): Focusing on executive functions.
[So] Source:Epilepsy Behav;54:71-9, 2016 Jan.
[Is] ISSN:1525-5069
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:PURPOSE: Increased evidence of subnormal neuropsychological functioning in new-onset childhood epilepsy has been obtained, although results are still rare and controversial. With a prospective study, we aimed to define the very early neuropsychological profile of children with benign epilepsy with centrotemporal spikes (BECTS), including executive functions (EF) because of their key role in learning. Additionally, we enrolled drug-naïve children, with a NREM sleep frequency of discharges <85% and with a Performance Intelligence Quotient equal or superior to 85, in order to exclude additional effects on the neuropsychological functioning. METHODS: Fifteen school-aged children with BECTS (mean age: 8.8years, standard deviation [SD]: 2.4years) and fifteen healthy children (mean age: 9.2years, [SD]: 2.5years) were enrolled and assessed with a comprehensive neuropsychological battery. The assessment included domain-specific standardized tests of language, EF, academic skills, visuomotor and visuospatial skills, and short-term memory. A p-value<0.05 was considered significant. RESULTS: Significant differences between patients and controls emerged with respect to 3 domains. Language was affected in color naming (p=.026), spoonerism (p=.003), and phonemic synthesis (p=.009). Executive functions appeared inadequate in the five point test with respect to the number of correct figures (p=.003) and errors (p=.008). In the domain of academic skills, significant differences between groups emerged regarding the number of mistakes in nonword writing (p=.001), nonword reading speed (p=.027), nonword reading number of mistakes (p=.019), and word reading errors (p=.023). DISCUSSION: Results showed that children with new-onset BECTS may demonstrate a range of neuropsychological dysfunctions, particularly affecting executive attention, despite a normal IQ, a low frequency of NREM sleep discharges, and the absence of drugs. These difficulties indicate a frontal dysfunction with cascading effects on language and academic skills. The inclusion of EF in the assessment battery and in the intervention since the very onset is warranted in order to avoid further and persistent academic difficulties.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1601
[Js] Journal subset:IM
[St] Status:In-Data-Review


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