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https://www.readbyqxmd.com/read/28078323/genetic-architecture-of-age-related-cognitive-decline-in-african-americans
#1
Towfique Raj, Lori B Chibnik, Cristin McCabe, Andus Wong, Joseph M Replogle, Lei Yu, Sujuan Gao, Frederick W Unverzagt, Barbara Stranger, Jill Murrell, Lisa Barnes, Hugh C Hendrie, Tatiana Foroud, Anna Krichevsky, David A Bennett, Kathleen S Hall, Denis A Evans, Philip L De Jager
OBJECTIVE: To identify genetic risk factors associated with susceptibility to age-related cognitive decline in African Americans (AAs). METHODS: We performed a genome-wide association study (GWAS) and an admixture-mapping scan in 3,964 older AAs from 5 longitudinal cohorts; for each participant, we calculated a slope of an individual's global cognitive change from neuropsychological evaluations. We also performed a pathway-based analysis of the age-related cognitive decline GWAS...
February 2017: Neurology. Genetics
https://www.readbyqxmd.com/read/28074573/structural-functional-and-clinical-characterization-of-a-novel-ptpn11-mutation-cluster-underlying-noonan-syndrome
#2
Luca Pannone, Gianfranco Bocchinfuso, Elisabetta Flex, Cesare Rossi, Giuseppina Baldassarre, Christina Lissewski, Francesca Pantaleoni, Federica Consoli, Francesca Lepri, Monia Magliozzi, Massimiliano Anselmi, Giovanni Sorge, Kadri Karaer, Goran Cuturilo, Alessandro Sartorio, Sigrid Tinschert, Maria Accadia, Maria C Digilio, Giuseppe Zampino, Alessandro De Luca, Hélène Cavé, Martin Zenker, Bruce D Gelb, Bruno Dallapiccola, Lorenzo Stella, Giovanni B Ferrero, Simone Martinelli, Marco Tartaglia
Germline mutations in PTPN11, the gene encoding the Src-homology 2 (SH2) domain-containing protein tyrosine phosphatase (SHP2), cause Noonan syndrome (NS), a relatively common, clinically variable, multisystem disorder. Here, we report on the identification of five different PTPN11 missense changes affecting residues Leu(261) , Leu(262) and Arg(265) in 16 unrelated individuals with clinical diagnosis of NS or with features suggestive for this disorder, specifying a novel disease-causing mutation cluster. Expression of the mutant proteins in HEK293T cells documented their activating role on MAPK signaling...
January 10, 2017: Human Mutation
https://www.readbyqxmd.com/read/28039315/neuromotor-and-cognitive-outcomes-of-early-treatment-in-tyrosine-hydroxylase-deficiency-type-b
#3
Vincenzo Leuzzi, Mario Mastrangelo, Maria Teresa Giannini, Riccardo Carbonetti, Georg F Hoffmann
No abstract text is available yet for this article.
December 30, 2016: Neurology
https://www.readbyqxmd.com/read/28025041/effect-of-lps-treatment-on-tyrosine-hydroxylase-expression-and-parkinson-like-behaviors
#4
Olivier Girard-Joyal, Nafissa Ismail
Puberty is a critical period of development during which the brain undergoes reorganizing and remodeling. Exposure to stress during this period is thought to interfere with normal brain development and increase susceptibility to mental illnesses. In female mice, pubertal exposure to lipopolysaccharide (LPS), a bacterial endotoxin, has been shown to alter sexual, anxiety-like, and depression-like behaviors and cognition in an enduring manner. However, the mechanisms underlying these effects remain unknown. The present study examined age and sex difference in tyrosine hydroxylase (TH) expression and dopamine-dependent and Parkinson-like behaviors following LPS treatment...
December 24, 2016: Hormones and Behavior
https://www.readbyqxmd.com/read/27984078/anti-inflammatory-and-protective-effects-of-mt-031-a-novel-multitarget-mao-a-and-ache-buche-inhibitor-in-scopolamine-mouse-model-and-inflammatory-cells
#5
Wei Liu, Alon Rabinovich, Yuval Nash, Dan Frenkel, Yuqiang Wang, Moussa B H Youdim, Orly Weinreb
Previous study demonstrated that the novel multitarget compound, MT-031 preserved in one molecule entity the beneficial properties of its parent drugs, rasagiline and rivastigmine, and exerted high dual potencies of monoamine oxidase-A (MAO-A) and cholinesterase (ChE) inhibition in acute-treated mice and neuroprotective effects against H2O2-induced neurotoxicity in human neuroblastoma SH-SY5Y cells. The present study aimed to further investigate the anti-inflammatory and protective effects of MT-031 in scopolamine mouse model and inflammatory cell cultures...
October 28, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27966074/brain-defective-insulin-signaling-is-associated-to-late-cognitive-impairment-in-post-septic-mice
#6
Fernanda S Neves, Patrícia T Marques, Fernanda Barros-Aragão, José Bruno Nunes, Aline M Venancio, Danielle Cozachenco, Rudimar L Frozza, Giselle F Passos, Robson Costa, Jade de Oliveira, Daiane F Engel, Andreza F De Bem, Claudia F Benjamim, Fernanda G De Felice, Sergio T Ferreira, Julia R Clarke, Claudia P Figueiredo
Sepsis survivors frequently develop late cognitive impairment. Because little is known on the mechanisms of post-septic memory deficits, there are no current effective approaches to prevent or treat such symptoms. Here, we subjected mice to severe sepsis induced by cecal ligation and puncture (CLP) and evaluated the sepsis-surviving animals in the open field, novel object recognition (NOR), and step-down inhibitory avoidance (IA) task at different times after surgery. Post-septic mice (30 days post-surgery) failed in the NOR and IA tests but exhibited normal performance when re-evaluated 45 days after surgery...
December 13, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27965573/7-8-dihydroxyflavone-ameliorates-cognitive-impairment-by-inhibiting-expression-of-tau-pathology-in-apoe-knockout-mice
#7
Yang Tan, Shuke Nie, Wende Zhu, Fang Liu, Hailong Guo, Jiewen Chu, Xue B Cao, Xingjun Jiang, Yunjian Zhang, Yuzhen Li
7,8-Dihydroxyflavone (7,8-DHF), a tyrosine kinase B agonist that mimics the neuroprotective properties of brain-derived neurotrophic factor, which can not efficiently deliver into the brain, has been reported to be useful in ameliorating cognitive impairment in many diseases. Researches have indicated that apolipoprotein E-knockout (ApoE-KO) mouse was associated with cognitive alteration via various mechanisms. Our present study investigated the possible mechanisms of cognitive impairment of ApoE-KO mouse fed with western type diet and the protective effects of 7,8-DHF in improving spatial learning and memory in ApoE-KO mouse...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27957651/carnosic-acid-protects-non-alcoholic-fatty-liver-induced-dopaminergic-neuron-injury-in-rats
#8
Ting Xu, Junjun Zhou, Jie Zhu, Shuai Zhang, Ning Zhang, Yan Zhao, Chunchun Ding, Xue Shi, Jihong Yao
Non-alcoholic fatty liver disease (NAFLD) has been reported to induce cognitive impairments of hippocampus and may influence central nervous system. In the present study, we investigated whether carnosic acid (CA) ameliorates dopaminergic neuron injury in a rat model of NAFLD. In order to induce NAFLD, rats were fed with high-fat diet (HFD) for 10 weeks. We found that continued CA administration reduced lipid accumulation marked by decreases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels, and an increase in high-density lipoprotein cholesterol (HDL-C) level in the serum...
December 13, 2016: Metabolic Brain Disease
https://www.readbyqxmd.com/read/27951531/reversal-learning-deficits-associated-with-increased-frontal-cortical-brain-derived-neurotrophic-factor-tyrosine-kinase-b-signaling-in-a-prenatal-cocaine-exposure-mouse-model
#9
Deirdre M McCarthy, Genevieve A Bell, Elisa N Cannon, Kaly A Mueller, Megan N Huizenga, Ghazaleh Sadri-Vakili, Debra A Fadool, Pradeep G Bhide
Prenatal cocaine exposure remains a major public health concern because of its adverse impact on cognitive function in children and adults. We report that prenatal cocaine exposure produces significant deficits in reversal learning, a key component of cognitive flexibility, in a mouse model. We used an olfactory reversal learning paradigm and found that the prenatally cocaine-exposed mice showed a marked failure to learn the reversed paradigm. Because brain-derived neurotrophic factor (BDNF) is a key regulator of cognitive functions, and because prenatal cocaine exposure increases the expression of BDNF and the phosphorylated form of its receptor, tyrosine kinase B (TrkB), we examined whether BDNF-TrkB signaling is involved in mediating the reversal learning deficit in prenatally cocaine-exposed mice...
December 13, 2016: Developmental Neuroscience
https://www.readbyqxmd.com/read/27912164/manganese-ii-chloride-alters-behavioral-and-neurochemical-parameters-in-larvae-and-adult-zebrafish
#10
Stefani Altenhofen, Melissa Talita Wiprich, Laura Roesler Nery, Carlos Eduardo Leite, Monica Ryff Moreira Roca Vianna, Carla Denise Bonan
Manganese (Mn) is an essential metal for organisms, but high levels can cause serious neurological damage. The aim of this study was to evaluate the effects of MnCl2 exposure on cognition and exploratory behavior in adult and larval zebrafish and correlate these findings with brain accumulation of Mn, overall brain tyrosine hydroxylase (TH) levels, dopamine (DA) levels, 3,4-dihydroxyphenylacetic acid (DOPAC) levels and cell death markers in the nervous system. Adults exposed to MnCl2 for 4days (0.5, 1.0 and 1...
January 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/27871887/a-silk-peptide-fraction-restores-cognitive-function-in-af64a-induced-alzheimer-disease-model-rats-by-increasing-expression-of-choline-acetyltransferase-gene
#11
Yeseul Cha, Sang Hoon Lee, Su Kil Jang, Haiyu Guo, Young-Hwan Ban, Dongsun Park, Gwi Yeong Jang, Sungho Yeon, Jeong-Yong Lee, Ehn-Kyoung Choi, Seong Soo Joo, Heon-Sang Jeong, Yun-Bae Kim
This study investigated the effects of a silk peptide fraction obtained by incubating silk proteins with Protease N and Neutrase (SP-NN) on cognitive dysfunction of Alzheimer disease model rats. In order to elucidate underlying mechanisms, the effect of SP-NN on the expression of choline acetyltransferase (ChAT) mRNA was assessed in F3.ChAT neural stem cells and Neuro2a neuroblastoma cells; active amino acid sequence was identified using HPLC-MS. The expression of ChAT mRNA in F3.ChAT cells increased by 3.79-fold of the control level by treatment with SP-NN fraction...
January 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27812290/tryptophan-metabolism-and-its-relationship-with-depression-and-cognitive-impairment-among-hiv-infected-individuals
#12
Michael R Keegan, Seetharamaiah Chittiprol, Scott L Letendre, Alan Winston, Dietmar Fuchs, Adriano Boasso, Jennifer Iudicello, Ronald J Ellis
OBJECTIVE: Cognitive impairment (CI) and major depressive disorder (MDD) remain prevalent in treated HIV-1 disease; however, the pathogenesis remains elusive. A possible contributing mechanism is immune-mediated degradation of tryptophan (TRP) via the kynurenine (KYN) pathway, resulting in decreased production of serotonin and accumulation of TRP degradation products. We explored the association of these biochemical pathways and their relationship with CI and MDD in HIV-positive (HIV+) individuals...
2016: International Journal of Tryptophan Research: IJTR
https://www.readbyqxmd.com/read/27807030/aging-affects-dopaminergic-neural-mechanisms-of-cognitive-flexibility
#13
Anne S Berry, Vyoma D Shah, Suzanne L Baker, Jacob W Vogel, James P O'Neil, Mustafa Janabi, Henry D Schwimmer, Shawn M Marks, William J Jagust
: Aging is accompanied by profound changes in the brain's dopamine system that affect cognitive function. Evidence of powerful individual differences in cognitive aging has sharpened focus on identifying biological factors underlying relative preservation versus vulnerability to decline. Dopamine represents a key target in these efforts. Alterations of dopamine receptors and dopamine synthesis are seen in aging, with receptors generally showing reduction and synthesis demonstrating increases...
December 14, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27798188/oxidation-of-kcnb1-potassium-channels-causes-neurotoxicity-and-cognitive-impairment-in-a-mouse-model-of-traumatic-brain-injury
#14
Wei Yu, Randika Parakramaweera, Shavonne Teng, Manasa Gowda, Yashsavi Sharad, Smita Thakker-Varia, Janet Alder, Federico Sesti
: The delayed rectifier potassium (K(+)) channel KCNB1 (Kv2.1), which conducts a major somatodendritic current in cortex and hippocampus, is known to undergo oxidation in the brain, but whether this can cause neurodegeneration and cognitive impairment is not known. Here, we used transgenic mice harboring human KCNB1 wild-type (Tg-WT) or a nonoxidable C73A mutant (Tg-C73A) in cortex and hippocampus to determine whether oxidized KCNB1 channels affect brain function. Animals were subjected to moderate traumatic brain injury (TBI), a condition characterized by extensive oxidative stress...
October 26, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27796759/increased-src-family-kinase-activity-disrupts-excitatory-synaptic-transmission-and-impairs-remote-fear-memory-in-forebrain-shp2-deficient-mice
#15
Xunyi Yan, Bin Zhang, Wen Lu, Lin Peng, Qian Yang, Wei Cao, Shen Lin, Wenyue Yu, Xiaoming Li, Yuehai Ke, Shengtian Li, Wei Yang, Jianhong Luo
Src homolog domain-containing phosphatase 2 (Shp2) signals a variety of cellular and physiological functions including learning and memory. Dysregulation of ERK signaling is known to be responsible for the cognitive deficits associated with gain-of-function mutated Shp2 mimicking Noonan syndrome. However, here, we report that CaMKIIα-cre induced knockout (CaSKO) of Shp2 in hippocampal pyramidal neurons resulted in increased Src activity, upregulated phosphorylation of N-methyl-D-aspartate receptors (NMDARs) at Y1325 of GluN2A and at Y1472 of GluN2B, disrupted the balance of synaptic transmission, and impaired long-term potentiation and remote contextual fear memory...
October 29, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27776132/tyrosine-binding-protein-sites-regulate-the-intracellular-trafficking-and-processing-of-amyloid-precursor-protein-through-a-novel-lysosome-directed-pathway
#16
Joshua H K Tam, M Rebecca Cobb, Claudia Seah, Stephen H Pasternak
The amyloid hypothesis posits that the production of β-amyloid (Aβ) aggregates leads to neurodegeneration and cognitive decline associated with AD. Aβ is produced by sequential cleavage of the amyloid precursor protein (APP) by β- and γ-secretase. While nascent APP is well known to transit to the endosomal/ lysosomal system via the cell surface, we have recently shown that APP can also traffic to lysosomes intracellularly via its interaction with AP-3. Because AP-3 interacts with cargo protein via interaction with tyrosine motifs, we mutated the three tyrosines motif in the cytoplasmic tail of APP...
2016: PloS One
https://www.readbyqxmd.com/read/27771511/high-fat-diet-induces-brain-insulin-resistance-and-cognitive-impairment-in-mice
#17
Vishal Kothari, Yuwen Luo, Talia Tornabene, Ann Marie O'Neill, Michael W Greene, Thangiah Geetha, Jeganathan Ramesh Babu
High fat diet-induced obesity is associated with insulin resistance (IR) and other chronic, diet related illnesses, including dementia. Alzheimer disease is the most common form of dementia, and is characterized by the presence of amyloid plaques and neurofibrillary tangles in brain. This study was designed to determine whether diet-induced changes in peripheral insulin sensitivity could contribute to alterations in brain insulin signaling and cognitive functions. Six week old, male C57BL/6NHsd mice were randomly assigned a high fat diet (40% energy from fat) with 42g/L liquid sugar (HFS) added to the drinking water or a normal chow diet (12% energy from fat) for 14weeks...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27756054/bioactive-effects-of-quercetin-in-the-central-nervous-system-focusing-on-the-mechanisms-of-actions
#18
REVIEW
Natarajan Suganthy, Kasi Pandima Devi, Seyed Fazel Nabavi, Nady Braidy, Seyed Mohammad Nabavi
Quercetin, a ubiquitous flavonoid that is widely distributed in plants is classified as a cognitive enhancer in traditional and oriental medicine. The protective effects of quercetin for the treatment of neurodegenerative disorders and cerebrovascular diseases have been demonstrated in both in vitro and in vivo studies. The free radical scavenging activity of quercetin has been well-documented, wherein quercetin has been observed to exhibit protective effects against oxidative stress mediated neuronal damage by modulating the expression of NRF-2 dependent antioxidant responsive elements, and attenuation of neuroinflammation by suppressing NF-κB signal transducer and activator of transcription-1 (STAT-1)...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27734680/empirical-valence-bond-simulations-of-the-hydride-transfer-step-in-the-monoamine-oxidase-a-catalyzed-metabolism-of-noradrenaline
#19
Matic Poberžnik, Miha Purg, Matej Repič, Janez Mavri, Robert Vianello
Monoamine oxidases (MAOs) A and B are flavoenzymes responsible for the metabolism of biogenic amines, such as dopamine, serotonin, and noradrenaline (NA), which is why they have been extensively implicated in the etiology and course of various neurodegenerative disorders and, accordingly, used as primary pharmacological targets to treat these debilitating cognitive diseases. The precise chemical mechanism through which MAOs regulate the amine concentration, which is vital for the development of novel inhibitors, is still not unambiguously determined in the literature...
November 10, 2016: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/27733612/sustained-gq-protein-signaling-disrupts-striatal-circuits-via-jnk
#20
Luigi Bellocchio, Andrea Ruiz-Calvo, Anna Chiarlone, Magali Cabanas, Eva Resel, Jean-René Cazalets, Cristina Blázquez, Yoon H Cho, Ismael Galve-Roperh, Manuel Guzmán
: The dorsal striatum is a major input structure of the basal ganglia and plays a key role in the control of vital processes such as motor behavior, cognition, and motivation. The functionality of striatal neurons is tightly controlled by various metabotropic receptors. Whereas the Gs/Gi-protein-dependent tuning of striatal neurons is fairly well known, the precise impact and underlying mechanism of Gq-protein-dependent signals remain poorly understood. Here, using different experimental approaches, especially designer receptor exclusively activated by designer drug (DREADD) chemogenetic technology, we found that sustained activation of Gq-protein signaling impairs the functionality of striatal neurons and we unveil the precise molecular mechanism underlying this process: a phospholipase C/Ca(2+)/proline-rich tyrosine kinase 2/cJun N-terminal kinase pathway...
October 12, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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