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https://www.readbyqxmd.com/read/28345177/pharmacogenomics-of-off-target-adrs
#1
REVIEW
Sarah L Garon, Rebecca K Pavlos, Katie D White, Nancy J Brown, Cosby A Stone, Elizabeth J Phillips
Off-target adverse drug reactions (ADRs) are associated with significant morbidity and costs to the healthcare system and their occurrence is not predictable based on the known pharmacological action of the drug's therapeutic effect. Off-target ADRs may or may not be associated with immunological memory although they can manifest with a variety of shared clinical features including maculopapular exanthema, severe cutaneous adverse reactions (SCARs), angioedema, pruritus, and bronchospasm. Discovery of specific genes associated with a particular ADR phenotype is a foundational component of clinical translation into screening programs for their prevention...
March 26, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28342849/comparative-effects-of-etoh-consumption-and-thiamine-deficiency-on-cognitive-impairment-oxidative-damage-and-%C3%AE-amyloid-peptide-overproduction-in-the-brain
#2
Yu-Shi Gong, Kun Hu, Lu-Qi Yang, Juan Guo, Yong-Qing Gao, Feng-Lin Song, Fang-Li Hou, Cui-Yi Liang
The effects of chronic EtOH consumption, associated or not with thiamine deficiency (TD), on cognitive impairment, oxidative damage, and β-amyloid (Aβ) peptide accumulation in the brain were investigated in male C57BL/6 mice. We established an alcoholic mouse model by feeding an EtOH liquid diet, a TD mouse model by feeding a thiamine-depleted liquid diet, and an EtOH treatment associated with TD mouse model by feeding a thiamine-depleted EtOH liquid diet for 7 weeks. The learning and memory functions of the mice were detected through the Y-maze test...
March 22, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28342765/hippocampal-insulin-resistance-and-altered-food-decision-making-as-players-on-obesity-risk
#3
REVIEW
Amanda Brondani Mucellini, Natasha Kim de Oliveira da Fonseca, Gisele Gus Manfro, Patrícia Pelufo Silveira
There are increasing evidences that hippocampus can modulate the decision of what, when and how much to eat, in addition to its already recognized role in learning and memory processes. Insulin also has been linked to brain functions such as feeding behavior and the imbalance of its mechanism of action on hippocampus is being related to cognitive dysfunction. The discussion here is whether changes in insulin action could contribute to intake dysregulation and obesogenic behavior as a primary consequence of impairing hippocampal functioning, aside from the role of this hormone on obesity development through peripheral metabolic pathways...
March 22, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28342697/recent-publications-from-the-alzheimer-s-disease-neuroimaging-initiative-reviewing-progress-toward-improved-ad-clinical-trials
#4
REVIEW
Michael W Weiner, Dallas P Veitch, Paul S Aisen, Laurel A Beckett, Nigel J Cairns, Robert C Green, Danielle Harvey, Clifford R Jack, William Jagust, John C Morris, Ronald C Petersen, Andrew J Saykin, Leslie M Shaw, Arthur W Toga, John Q Trojanowski
INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative (ADNI) has continued development and standardization of methodologies for biomarkers and has provided an increased depth and breadth of data available to qualified researchers. This review summarizes the 450+ publications using ADNI data during 2014 and 2015. METHODS: We used standard searches to find publications using ADNI data. RESULTS: (1) Structural and functional changes, including subtle changes to hippocampal shape and texture, atrophy in areas outside of hippocampus, and disruption to functional networks, are detectable in presymptomatic subjects before hippocampal atrophy; (2) In subjects with abnormal β-amyloid deposition (Aβ+), biomarkers become abnormal in the order predicted by the amyloid cascade hypothesis; (3) Cognitive decline is more closely linked to tau than Aβ deposition; (4) Cerebrovascular risk factors may interact with Aβ to increase white-matter (WM) abnormalities which may accelerate Alzheimer's disease (AD) progression in conjunction with tau abnormalities; (5) Different patterns of atrophy are associated with impairment of memory and executive function and may underlie psychiatric symptoms; (6) Structural, functional, and metabolic network connectivities are disrupted as AD progresses...
March 22, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28341160/metabolic-network-failures-in-alzheimer-s-disease-a-biochemical-road%C3%A2-map
#5
Jon B Toledo, Matthias Arnold, Gabi Kastenmüller, Rui Chang, Rebecca A Baillie, Xianlin Han, Madhav Thambisetty, Jessica D Tenenbaum, Karsten Suhre, J Will Thompson, Lisa St John-Williams, Siamak MahmoudianDehkordi, Daniel M Rotroff, John R Jack, Alison Motsinger-Reif, Shannon L Risacher, Colette Blach, Joseph E Lucas, Tyler Massaro, Gregory Louie, Hongjie Zhu, Guido Dallmann, Kristaps Klavins, Therese Koal, Sungeun Kim, Kwangsik Nho, Li Shen, Ramon Casanova, Sudhir Varma, Cristina Legido-Quigley, M Arthur Moseley, Kuixi Zhu, Marc Y R Henrion, Sven J van der Lee, Amy C Harms, Ayse Demirkan, Thomas Hankemeier, Cornelia M van Duijn, John Q Trojanowski, Leslie M Shaw, Andrew J Saykin, Michael W Weiner, P Murali Doraiswamy, Rima Kaddurah-Daouk
INTRODUCTION: The Alzheimer's Disease Research Summits of 2012 and 2015 incorporated experts from academia, industry, and nonprofit organizations to develop new research directions to transform our understanding of Alzheimer's disease (AD) and propel the development of critically needed therapies. In response to their recommendations, big data at multiple levels are being generated and integrated to study network failures in disease. We used metabolomics as a global biochemical approach to identify peripheral metabolic changes in AD patients and correlate them to cerebrospinal fluid pathology markers, imaging features, and cognitive performance...
March 21, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28338897/specialized-information-processing-deficits-and-distinct-metabolomic-profiles-following-tm-domain-disruption-of-nrg1
#6
Colm M P O'Tuathaigh, Naina Mathur, Matthew J O'Callaghan, Lynsey MacIntyre, Richard Harvey, Donna Lai, John L Waddington, Benjamin S Pickard, David G Watson, Paula M Moran
Although there is considerable genetic and pathologic evidence for an association between neuregulin 1 (NRG1) dysregulation and schizophrenia, the underlying molecular and cellular mechanisms remain unclear. Mutant mice containing disruption of the transmembrane (TM) domain of the NRG1 gene constitute a heuristic model for dysregulation of NRG1-ErbB4 signaling in schizophrenia. The present study focused on hitherto uncharacterized information processing phenotypes in this mutant line. Using a mass spectrometry-based metabolomics approach, we also quantified levels of unique metabolites in brain...
March 11, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/28337257/subcutaneous-liraglutide-ameliorates-methylglyoxal-induced-alzheimer-like-tau-pathology-and-cognitive-impairment-by-modulating-tau-hyperphosphorylation-and-glycogen-synthase-kinase-3%C3%AE
#7
Liqin Qi, Zhou Chen, Yanping Wang, Xiaoying Liu, Xiaohong Liu, Linfang Ke, Zhongjie Zheng, Xiaowei Lin, Yu Zhou, Lijuan Wu, Libin Liu
Memory deterioration and synapse damage with accumulation of β-amyloid and hyperphosphorylated tau are hallmark lesions of Alzheimer's disease (AD). Methylglyoxal (MG), a key intermediate of glucose metabolism, is elevated in AD brains and modifies Aβ42, increasing misfolding and leading to the accumulation of senile plaques. Liraglutide, an analog of glucagon-like peptide-1 (GLP-1), is neurotrophic and neuroprotective. However, whether liraglutide can protect against AD-like memory-related deficits and tau hyperphosphorylation caused by MG in vivo is not known...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28334149/higher-striatal-iron-concentration-is-linked-to-frontostriatal-underactivation-and-poorer-memory-in-normal-aging
#8
Grégoria Kalpouzos, Benjamín Garzón, Rouslan Sitnikov, Carmel Heiland, Alireza Salami, Jonas Persson, Lars Bäckman
In the brain, intracellular iron is essential for cellular metabolism. However, an overload of free iron is toxic, inducing oxidative stress and cell death. Although an increase of striatal iron has been related to atrophy and impaired cognitive performance, the link between elevated iron and altered brain activity in aging remains unexplored. In a sample of 37 younger and older adults, we examined whether higher striatal iron concentration could underlie age-related differences in frontostriatal activity induced by mental imagery of motor and non-motor scenes, and poorer recall of the scenes...
February 23, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28333387/pathophysiological-fundamentals-of-diabetic-cardiomyopathy
#9
Xinyue Hu, Tao Bai, Zheng Xu, Qiuju Liu, Yang Zheng, Lu Cai
Diabetic cardiomyopathy (DCM) was first recognized more than four decades ago and occurred independent of cardiovascular diseases or hypertension in both type 1 and type 2 diabetic patients. The exact mechanisms underlying this disease remain incompletely understood. Several pathophysiological bases responsible for DCM have been proposed, including the presence of hyperglycemia, nonenzymatic glycosylation of large molecules (e.g., proteins), energy metabolic disturbance, mitochondrial damage and dysfunction, impaired calcium handling, reactive oxygen species formation, inflammation, cardiac cell death, and cardiac hypertrophy and fibrosis, leading to impairment of cardiac contractile functions...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28329324/age-related-biomarkers-in-llfs-families-with-exceptional-cognitive-abilities
#10
Sandra Barral, Jatinder Singh, Erin Fagan, Stephanie Cosentino, Stacy L Andersen-Toomey, Mary K Wojczynski, Mary Feitosa, Candace M Kammerer, Nicole Schupf
Background: We previously demonstrated familial aggregation of memory performance within the Long Life Family Study (LLFS), suggesting that exceptional cognition (EC) may contribute to their exceptional longevity. Here, we investigated whether LLFS families with EC may also exhibit more favorable profiles of other age-related biomarkers. Methods: Nondemented offspring of the LLFS probands scoring 1.5 SD above the mean in a cognitive phenotype were classified as participants with EC...
March 10, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28326037/differences-on-brain-connectivity-in-adulthood-are-present-in-subjects-with-iron-deficiency-anemia-in-infancy
#11
Cecilia Algarin, Keerthana Deepti Karunakaran, Sussanne Reyes, Cristian Morales, Betsy Lozoff, Patricio Peirano, Bharat Biswal
Iron deficiency continues to be the most prevalent micronutrient deficit worldwide. Since iron is involved in several processes including myelination, dopamine neurotransmission and neuronal metabolism, the presence of iron deficiency anemia (IDA) in infancy relates to long-lasting neurofunctional effects. There is scarce data regarding whether these effects would extend to former iron deficient anemic human adults. Resting state functional magnetic resonance imaging (fMRI) is a novel technique to explore patterns of functional connectivity...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28324109/sex-specific-life-course-changes-in-the-neuro-metabolic-phenotype-of-glut3-null-heterozygous-mice-ketogenic-diet-ameliorates-electroencephalographic-seizures-and-improves-sociability
#12
Yun Dai, Yuanzi Zhao, Masatoshi Tomi, Bo-Chul Shin, Shanthie Thamotharan, Andrey Mazarati, Raman Sankar, Elizabeth A Wang, Carlos Cepeda, Michael S Levine, Jingjing Zhang, Andrew Frew, Jeffry R Alger, Peter Clark, Monica Sondhi, Sudatip Kositamongkol, Leah Leibovitch, Sherin U Devaskar
We tested the hypothesis that exposure of glut3+/- mice to a ketogenic diet ameliorates autism-like features which includes aberrant behavior and electrographic seizures. We first investigated the life course sex-specific changes in basal plasma-CSF-brain metabolic profile, brain glucose transport/uptake, glucose and monocarboxylate transporter proteins, and ATP in the presence or absence of systemic insulin administration. Glut3+/- male but not female mice (5m of age) displayed reduced CSF glucose/lactate concentrations with no change in brain Glut1, Mct2, glucose uptake or ATP...
January 24, 2017: Endocrinology
https://www.readbyqxmd.com/read/28320264/molecular-mechanisms-of-neuroplasticity-an-expanding-universe
#13
REVIEW
N V Gulyaeva
Biochemical processes in synapses and other neuronal compartments underlie neuroplasticity (functional and structural alterations in the brain enabling adaptation to the environment, learning, memory, as well as rehabilitation after brain injury). This basic molecular level of brain plasticity covers numerous specific proteins (enzymes, receptors, structural proteins, etc.) participating in many coordinated and interacting signal and metabolic processes, their modulation forming a molecular basis for brain plasticity...
March 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28315844/cerebral-glucose-metabolism-and-cognition-in-newly-diagnosed-parkinson-s-disease-icicle-pd-study
#14
M J Firbank, A J Yarnall, R A Lawson, G W Duncan, T K Khoo, G S Petrides, J T O'Brien, R A Barker, R J Maxwell, D J Brooks, D J Burn
OBJECTIVE: To assess reductions of cerebral glucose metabolism in Parkinson's disease (PD) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and their associations with cognitive decline. METHODS: FDG-PET was performed on a cohort of 79 patients with newly diagnosed PD (mean disease duration 8 months) and 20 unrelated controls. PD participants were scanned while on their usual dopaminergic medication. Cognitive testing was performed at baseline, and after 18 months using the Cognitive Drug Research (CDR) and Cambridge Neuropsychological Test Automated Battery (CANTAB) computerised batteries, the Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA)...
April 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28315455/7-8-dihydroxyflavone-facilitates-the-action-exercise-to-restore-plasticity-and-functionality-implications-for-early-brain-trauma-recovery
#15
Gokul Krishna, Rahul Agrawal, Yumei Zhuang, Zhe Ying, Afshin Paydar, Neil G Harris, Luiz Fernando F Royes, Fernando Gomez-Pinilla
Metabolic dysfunction accompanying traumatic brain injury (TBI) severely impairs the ability of injured neurons to comply with functional demands. This limits the success of rehabilitative strategies by compromising brain plasticity and function, and highlights the need for early interventions to promote energy homeostasis. We sought to examine whether the TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF) normalizes brain energy deficits and restablishes more normal patterns of functional connectivity, while enhancing the effects of exercise during post-TBI period...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28304289/episodic-memory-dysfunction-in%C3%A2-behavioral-variant-frontotemporal-dementia-a-clinical-and-fdg-pet-study
#16
Marta Fernández-Matarrubia, Jordi A Matías-Guiu, María Nieves Cabrera-Martín, Teresa Moreno-Ramos, María Valles-Salgado, José Luis Carreras, Jorge Matías-Guiu
BACKGROUND: Episodic memory disturbance is still considered as an exclusion criterion for behavioral variant frontotemporal dementia (bvFTD), but growing evidence suggests that memory can be impaired. OBJECTIVE: Our main purposes were to assess episodic memory in a group of bvFTD patients comparatively with Alzheimer's disease (AD) patients, and analyze the relationship between episodic memory and brain metabolism measured using positron emission tomography imaging with 18F-fluorodeoxyglucose (FDG-PET)...
March 10, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28302762/brain-fdg-pet-metabolic-abnormalities-in-macrophagic-myofasciitis-are-they-stable
#17
Paul Blanc-Durand, Axel Van Der Gucht, Mehdi Aoun Sebaiti, Mukedaisi Abulizi, Francois-Jérome Authier, Emmanuel Itti
We address this letter in addition to our recent published study (1). The aim is to add some insight to the evolution of the brain abnormalities that are observed with macrophagic myofasciitis (MMF). MMF is a chronic disease whom evolution is slow and symptoms first may occurs from months to year after a vaccination containing aluminium hydroxid adjuvants (2). Nevertheless, its evolution is not fully understood or known. MMF associated cognitive dysfunction (MACD) is based on a tripod combining dysexecutive syndrom, visual memory impairment and interhemispheric disconnection...
March 16, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28301775/the-microbiome-and-host-behavior
#18
Helen E Vuong, Jessica M Yano, Thomas C Fung, Elaine Y Hsiao
The microbiota is increasingly recognized for its ability to influence the development and function of the nervous system and several complex host behaviors. In this review, we discuss emerging roles for the gut microbiota in modulating host social and communicative behavior, stressor-induced behavior, and performance in learning and memory tasks. We summarize effects of the microbiota on host neurophysiology, including brain microstructure, gene expression, and neurochemical metabolism across regions of the amygdala, hippocampus, frontal cortex, and hypothalamus...
March 8, 2017: Annual Review of Neuroscience
https://www.readbyqxmd.com/read/28299814/functional-neuroanatomical-associations-of-working-memory-in-early-onset-alzheimer-s-disease
#19
Christopher Kobylecki, Cathleen Haense, Jennifer M Harris, Cheryl L Stopford, Shailendra H Segobin, Matthew Jones, Anna M T Richardson, Alexander Gerhard, José Anton-Rodriguez, Jennifer C Thompson, Karl Herholz, Julie S Snowden
OBJECTIVE: To characterize metabolic correlates of working memory impairment in clinically defined subtypes of early-onset Alzheimer's disease. BACKGROUND: Established models of working memory suggest a key role for frontal lobe function, yet the association in Alzheimer's disease between working memory impairment and visuospatial and language symptoms suggests that temporoparietal neocortical dysfunction may be responsible. METHODS: Twenty-four patients with predominantly early-onset Alzheimer's disease were clinically classified into groups with predominantly amnestic, multidomain or visual deficits...
March 16, 2017: International Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28289278/cafeteria-diet-and-probiotic-therapy-cross-talk-among-memory-neuroplasticity-serotonin-receptors-and-gut-microbiota-in-the-rat
#20
J E Beilharz, N O Kaakoush, J Maniam, M J Morris
The western diet is known to have detrimental effects on cognition and the gut microbiota, but few studies have investigated how these may be related. Here, we examined whether a probiotic could prevent diet-induced memory deficits. Rats were pre-exposed to vehicle, low or high doses of VSL#3 for 2 weeks before half were switched from chow to a cafeteria diet (Caf) for 25 days; VSL#3 treatment continued until death. High-dose VSL#3 prevented the diet-induced memory deficits on the hippocampal-dependent place task, but the probiotic caused deficits on the perirhinal-dependent object task, irrespective of diet or dose...
March 14, 2017: Molecular Psychiatry
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