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https://www.readbyqxmd.com/read/29352507/nuclear-and-membrane-estrogen-receptor-antagonists-induce-similar-mtorc2-activation-reversible-changes-in-synaptic-protein-expression-and-actin-polymerization-in-the-mouse-hippocampus
#1
Fang-Zhou Xing, Yan-Gang Zhao, Yuan-Yuan Zhang, Li He, Ji-Kai Zhao, Meng-Ying Liu, Yan Liu, Ji-Qiang Zhang
AIMS: Estrogens play pivotal roles in hippocampal synaptic plasticity through nuclear receptors (nERs; including ERα and ERβ) and the membrane receptor (mER; also called GPR30), but the underlying mechanism and the contributions of nERs and mER remain unclear. Mammalian target of rapamycin complex 2 (mTORC2) is involved in actin cytoskeleton polymerization and long-term memory, but whether mTORC2 is involved in the regulation of hippocampal synaptic plasticity by ERs is unclear. METHODS: We treated animals with nER antagonists (MPP/PHTPP) or the mER antagonist (G15) alone or in combination with A-443654, an activator of mTORC2...
January 19, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29352484/melatonin-ameliorates-a%C3%AE-42-induced-alteration-of-%C3%AE-app-processing-secretases-via-the-melatonin-receptor-through-the-pin1-gsk3%C3%AE-nf-%C3%AE%C2%BAb-pathway-in-sh-sy5y-cells
#2
Vorapin Chinchalongporn, Mayuri Shukla, Piyarat Govitrapong
Melatonin is involved in the physiological regulation of the β- amyloid precursor protein (βAPP) cleaving secretases which are responsible for generation of the neurotoxic amyloid beta (Aβ) peptide, one of the hallmarks of Alzheimer's disease (AD) pathology. In this study, we aimed to determine the underlying mechanisms of this regulation under pathological conditions. We establish that melatonin prevents Aβ42 -induced down-regulation of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) as well as up-regulation of β-site APP-cleaving enzyme 1 (BACE1) and presenilin 1 (PS1) in SH-SY5Y cell cultures...
January 20, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29352444/activation-of-the-anti-aging-and-cognition-enhancing-gene-klotho-by-crispr-dcas9-transcriptional-effector-complex
#3
Ci-Di Chen, Ella Zeldich, Yuexuan Li, Andrea Yuste, Carmela R Abraham
Multiple lines of evidence show that the anti-aging and cognition-enhancing protein Klotho fosters neuronal survival, increases the anti-oxidative stress defense, and promotes remyelination of demyelinated axons. Thus, upregulation of the Klotho gene can potentially alleviate the symptoms and/or prevent the progression of age-associated neurodegenerative diseases such as Alzheimer's disease and demyelinating diseases such as multiple sclerosis. Here we used a CRISPR-dCas9 complex to investigate single-guide RNA (sgRNA) targeting the Klotho promoter region for efficient transcriptional activation of the Klotho gene...
January 19, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29352390/a-spatial-registration-toolbox-for-structural-mr-imaging-of-the-aging-brain
#4
Marco Ganzetti, Quanying Liu, Dante Mantini
During aging the brain undergoes a series of structural changes, in size, shape as well as tissue composition. In particular, cortical atrophy and ventricular enlargement are often present in the brain of elderly individuals. This poses serious challenges in the spatial registration of structural MR images. In this study, we addressed this open issue by proposing an enhanced framework for MR registration and segmentation. Our solution was compared with other approaches based on the tools available in SPM12, a widely used software package...
January 19, 2018: Neuroinformatics
https://www.readbyqxmd.com/read/29352267/differential-susceptibility-of-striatal-hippocampal-and-cortical-neurons-to-caspase-6
#5
Anastasia Noël, Libin Zhou, Bénédicte Foveau, P Jesper Sjöström, Andréa C LeBlanc
Active cysteinyl protease Caspase-6 is associated with early Alzheimer and Huntington diseases. Higher entorhinal cortex and hippocampal Caspase-6 levels correlate with lower cognitive performance in aged humans. Caspase-6 induces axonal degeneration in human primary neuron cultures and causes inflammation and neurodegeneration in mouse hippocampus, and age-dependent memory impairment. To assess whether Caspase-6 causes damage to another neuronal system, a transgenic knock-in mouse overexpressing a self-activated form of Caspase-6 five-fold in the striatum, the area affected in Huntington disease, and 2...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352259/plasma-mcp-1-and-cognitive-decline-in-patients-with-alzheimer-s-disease-and-mild-cognitive-impairment-a-two-year-follow-up-study
#6
Wei-Ju Lee, Yi-Chu Liao, Yen-Feng Wang, I-Feng Lin, Shuu-Jiun Wang, Jong-Ling Fuh
Monocyte chemoattractant protein-1 (MCP-1, also known as chemokine CCL2) is a vital chemokine that mediates inflammation in Alzheimer's disease (AD). We analyzed the associations between the baseline plasma MCP-1 level, longitudinal cognitive changes, and genetic effects of CCL2 rs1024611 and its receptor, CC-chemokine receptor 2 (CCR2) rs1799864, in AD. In total, 310 AD patients and 66 mild cognitive impairment (MCI) patients were followed for 2 years, and 120 controls were recruited at baseline for comparison...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352234/bi-exponential-3d-t1%C3%AF-mapping-of-whole-brain-at-3%C3%A2-t
#7
Rajiv G Menon, Azadeh Sharafi, Johannes Windschuh, Ravinder R Regatte
Detection of multiple relaxation pools using MRI is useful in a number of neuro-pathologies including multiple sclerosis (MS), Alzheimer's, and stroke. In this study we evaluate the feasibility of using T1ρ imaging for the detection of bi-exponential decays in the human brain. A prospective T1ρ imaging study was performed on model relaxation phantoms (eggs) and 7 healthy volunteers. The data was fitted using a single pool and a 2-pool model to estimate mono- and bi-exponential T1ρ maps, respectively. Bi-exponential decays were identified in the gray matter (GM) and white matter (WM) of the brain with 40...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29351877/rest-a-master-transcriptional-regulator-in-neurodegenerative-disease
#8
REVIEW
Jee-Yeon Hwang, R Suzanne Zukin
The restrictive element-1 silencing transcription factor)/NRSF (neuron-restrictive silencing factor (NRSF) is a transcriptional repressor which acts via epigenetic remodeling to silence target genes. Emerging evidence indicates that REST is a master transcriptional regulator of neuron-specific genes not only in neurogenesis and neuronal differentiation, but also in differentiated neurons during the critical period in postnatal brain development, where it plays a role in fine-tuning of genes involved in synaptic plasticity, and in normal aging, where it promotes neuroprotection by repressing genes involved in oxidative stress and β-amyloid toxicity...
January 16, 2018: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29351720/structural-interconversion-in-alzheimer-s-amyloid-%C3%AE-16-35-peptide-in-an-aqueous-solution
#9
Nelson Alves, Rafael B Frigori
Structural properties of Aβ(16-35) fragment are investigated as a model for the amyloid-β peptide excluding its coil-inducing terminals. Our Replica-Exchange Molecular Dynamics simulations using all-atoms and explicit aqueous solvation widely reduce any structural bias. The principal folding pathway shows direct conversion of coil to β-sheet, without the long proposed helix intermediates. Our PCA analysis indicates that the fragment is also intrinsically disordered, as the full amyloid-β peptide. Thus, the observed folding mechanism lacks free-energy barriers and any peaks in the thermal capacity...
January 19, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29351627/repair-kinetics-of-dna-double-strand-breaks-and-incidence-of-apoptosis-in-mouse-neural-stem-progenitor-cells-and-their-differentiated-neurons-exposed-to-ionizing-radiation
#10
Hiroki Kashiwagi, Kazunori Shiraishi, Kenta Sakaguchi, Tomoya Nakahama, Seiji Kodama
Neuronal loss leads to neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease and Huntington's disease. Because of their long lifespans, neurons are assumed to possess highly efficient DNA repair ability and to be able to protect themselves from deleterious DNA damage such as DNA double-strand breaks (DSBs) produced by intrinsic and extrinsic sources. However, it remains largely unknown whether the DSB repair ability of neurons is more efficient compared with that of other cells. Here, we investigated the repair kinetics of X-ray-induced DSBs in mouse neural cells by scoring the number of phosphorylated 53BP1 foci post irradiation...
January 17, 2018: Journal of Radiation Research
https://www.readbyqxmd.com/read/29351585/core-differences-in-synaptic-signaling-between-primary-visual-and-dorsolateral-prefrontal-cortex
#11
Sheng-Tao Yang, Min Wang, Constantinos D Paspalas, Johanna L Crimins, Marcus T Altman, James A Mazer, Amy F T Arnsten
Neurons in primary visual cortex (V1) are more resilient than those in dorsolateral prefrontal cortex (dlPFC) in aging, schizophrenia and Alzheimer's disease. The current study compared glutamate and neuromodulatory actions in macaque V1 to those in dlPFC, and found striking regional differences. V1 neuronal firing to visual stimuli depended on AMPA receptors, with subtle NMDA receptor contributions, while dlPFC depends primarily on NMDA receptors. Neuromodulatory actions also differed between regions. In V1, cAMP signaling increased neuronal firing, and the phosphodiesterase PDE4A was positioned to regulate cAMP effects on glutamate release from axons...
January 17, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29351484/the-serum-metabolomics-signature-of-type-2-diabetes-is-obscured-in-alzheimer-s-disease
#12
Jill K Morris, Brian D Piccolo, Kartik Shankar, John P Thyfault, Sean H Adams
There is evidence for systemic metabolic impairment in Alzheimer's disease (AD), and Type 2 Diabetes (T2D) increases AD risk. Although studies analyzing blood metabolomics signatures have shown differences between cognitively healthy (CH) and AD subjects, these signatures have not been compared to individuals with T2D. We utilized untargeted analysis platforms (primary metabolism and complex lipids) to characterize the serum metabolome of 126 overnight fasted elderly subjects classified into 4 groups based upon AD status (CH or AD) and T2D status (Nondiabetic [ND] or T2D)...
December 26, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29351469/inhibition-of-mtor-protects-the-blood-brain-barrier-in-models-of-alzheimer-s-disease-and-vascular-cognitive-impairment
#13
Candice E Van Skike, Jordan B Jahrling, Angela B Olson, Naomi L Sayre, Stacy A Hussong, Zoltan I Ungvari, James D Lechleiter, Veronica Galvan
An intact blood-brain barrier (BBB) limits entry of pro-inflammatory and neurotoxic blood-derived factors into the brain parenchyma. The BBB is damaged in Alzheimer's disease (AD), which contributes significantly to the progression of AD pathologies and cognitive decline. However, the mechanisms underlying BBB breakdown in AD remain elusive and no interventions are available for treatment or prevention. We and others recently established that inhibition of the mammalian/mechanistic target of rapamycin (mTOR) pathway with rapamycin yields significant neuroprotective effects, improving cerebrovascular and cognitive function in mouse models of AD...
December 22, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29351426/the-effects-of-heat-and-cold-on-health-with-special-reference-to-finnish-sauna-bathing
#14
Ilkka Heinonen, Jari A Laukkanen
Environmental stress such as extremely warm or cold temperature is often considered a challenge to human health and body homeostasis. However, human body can adapt relatively well to heat and cold environments and recent studies have also elucidated that particularly heat stress might be even highly beneficial for human health. Consequently, the aim of the present brief review is first to discuss general cardiovascular and other responses to acute heat stress, followed by a review of beneficial effects of Finnish sauna bathing on general and cardiovascular health and mortality as well as dementia and Alzheimer's disease risk...
December 20, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29351092/political-ideology-confidence-in-science-and-participation-in-alzheimer-disease-research-studies
#15
Matthew Gabel, Jonathan Gooblar, Catherine M Roe, Natalie J Selsor, John C Morris
BACKGROUND: Americans' confidence in science varies based on their political ideology. This ideological divide has potentially important effects on citizens' engagement with and participation in clinical studies of Alzheimer disease (AD). METHODS: A probability sample of 1583 Americans was surveyed about their willingness to participate in longitudinal AD research and about their political attitudes. These survey results were compared with a survey of 382 participants in a longitudinal AD study at the Knight Alzheimer Disease Research Center...
January 18, 2018: Alzheimer Disease and Associated Disorders
https://www.readbyqxmd.com/read/29351091/circadian-rhythms-disturbances-in-alzheimer-disease-current-concepts-diagnosis-and-management
#16
Ángela Milán-Tomás, Colin M Shapiro
The purpose of this review is to provide an overview of the research regarding circadian rhythms in Alzheimer disease (AD). Furthermore, this paper explores the role of melatonin in the pathogenesis of AD and the limitation of trials addressing circadian rhythms disturbances in the AD population. A literature search using Medline with PubMed and Embase was carried out identifying papers focusing on circadian rhythms in AD. Sleep disorders and especially circadian rhythm disturbances are very common in the elderly population but definitely more pronounced in patients with AD...
January 18, 2018: Alzheimer Disease and Associated Disorders
https://www.readbyqxmd.com/read/29350764/the-protective-effect-of-antarctic-krill-oil-on-cognitive-function-by-inhibiting-oxidative-stress-in-the-brain-of-senescence-accelerated-prone-mouse-strain-8-samp8-mice
#17
Qian Li, Fengjuan Wu, Min Wen, Teruyoshi Yanagita, Changhu Xue, Tiantian Zhang, Yuming Wang
Alzheimer's disease (AD) is a common neurodegenerative disorder, and oxidative stress plays a vital role in its progression. Antarctic krill oil (AKO) is rich in polyunsaturated fatty acids, which has various biological activities, such as improving insulin sensitivity, alleviating inflammation and ameliorating oxidative stress. In this study, the protective effect of AKO against AD were investigated in senescence-accelerated prone mouse strain 8 (SAMP8) mice. Results showed that treatment with AKO could effectively ameliorate learning and memory deficits and ease the anxiety in SAMP8 mice by Morris water maze, Barnes maze test and open-field test...
January 19, 2018: Journal of Food Science
https://www.readbyqxmd.com/read/29350557/omega-3-polyunsaturated-fatty-acids-and-their-health-benefits
#18
Fereidoon Shahidi, Priyatharini Ambigaipalan
Omega-3 polyunsaturated fatty acids (PUFAs) include α-linolenic acid (ALA; 18:3 ω-3), stearidonic acid (SDA; 18:4 ω-3), eicosapentaenoic acid (EPA; 20:5 ω-3), docosapentaenoic acid (DPA; 22:5 ω-3), and docosahexaenoic acid (DHA; 22:6 ω-3). In the past few decades, many epidemiological studies have been conducted on the myriad health benefits of omega-3 PUFAs. In this review, we summarized the structural features, properties, dietary sources, metabolism, and bioavailability of omega-3 PUFAs and their effects on cardiovascular disease, diabetes, cancer, Alzheimer's disease, dementia, depression, visual, and neurological development, as well as maternal and child health...
January 18, 2018: Annual Review of Food Science and Technology
https://www.readbyqxmd.com/read/29350177/antidepressant-medication-in-a-german-cohort-of-patients-with-alzheimer-s-disease%C3%A2
#19
Philipp Hessmann, Richard Dodel, Erika Baum, Matthias J Müller, Greta Paschke, Bernhard Kis, Jan Zeidler, Mike Klora, Jens-Peter Reese, Monika Balzer-Geldsetzer
OBJECTIVE: The use of antidepressant drugs in dementia patients is associated with the risk of adverse events, and the evidence for relevant effects is scarce. We aimed to determine the associations between the prescription of antidepressants and patients' sociodemographic (e.g., age, gender, living situation) and clinical characteristics (e.g., disease severity, neuropsychiatric symptoms). MATERIALS AND METHODS: We included 395 institutionalized and community-dwelling patients with Alzheimer's disease (AD) across all severity stages of dementia in a cross-sectional study design...
January 19, 2018: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29350060/-so-they-are-not-alive-dementia-reality-disjunctions-and-conversational-strategies
#20
Lars-Christer Hydén, Christina Samuelsson
In some conversations involving persons with Alzheimer's disease, the participants may have to deal with the difficulty that they do not share a common ground in terms of not only who is alive or dead, but even more, who could possibly be alive. It is as if the participants face a reality disjunction. There are very few empirical studies of this difficulty in conversations involving persons with Alzheimer's disease or other kinds of dementia diagnoses. Often studies of confabulation have a focus on the behavior and experience of the healthy participants, but rarely on the interaction and the collaborative contributions made by the person with dementia...
January 1, 2018: Dementia
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