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Neurobiology of Aging

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https://www.readbyqxmd.com/read/28108040/genetic-analysis-of-chchd2-and-chchd10-in-italian-patients-with-parkinson-s-disease
#1
Elisa Rubino, Livia Brusa, Ming Zhang, Silvia Boschi, Flora Govone, Alessandro Vacca, Annalisa Gai, Lorenzo Pinessi, Leonardo Lopiano, Ekaterina Rogaeva, Innocenzo Rainero
In recent years, CHCHD2 and CHCHD10 mutations were reported to be associated with a broad spectrum of neurodegenerative diseases, including Parkinson's disease (PD), although with conflicting results in different populations. The present study aimed to evaluate CHCHD2 and CHCHD10 coding variants in Italian patients with PD. All the coding regions and flanking intronic splice sites of CHCHD2 and CHCHD10 were sequenced. None of our 119 PD cases carried CHCHD2 mutations, whereas 1 sporadic PD patient showed the Pro34Ser substitution in CHCHD10...
January 5, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28110104/quercetin-3-o-glucuronide-promotes-the-proliferation-and-migration-of-neural-stem-cells
#2
Samrat Baral, Ramesh Pariyar, Jaehyo Kim, Ho-Sub Lee, Jungwon Seo
Quercetin is a bioactive compound exerting therapeutic effects on in vivo animal models of neurodegeneration or neurotoxicity. However, the narrow therapeutic dose-range of quercetin has been a point of concern since previous studies have demonstrated that quercetin induces cytotoxicity in vitro. Quercetin is metabolized to quercetin glucuronates such as quercetin-3-O-glucuronide (Q3GA), primarily detected in the plasma and the brain. Here, we examined whether and how quercetin or Q3GA regulates neural stem cells (NSCs) in vivo and in vitro...
January 3, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28110103/the-retromer-complex-system-in-a-transgenic-mouse-model-of-ad-influence-of-age
#3
Jin Chu, Domenico Praticò
Deficiencies of the retrograde transport mediated by the retromer complex have been described in Alzheimer's disease (AD). Genetic manipulation of retromer modulates brain amyloidosis in Tg2576 mice. However, whether the complex is altered during the development of the AD-like phenotype remains unknown. In this study we assayed the expression levels of the vacuolar sorting protein 35 (VPS35), VPS26, VPS29, and its cargo proteins, cation independent mannose 6-phosphate receptor, sortilin-related receptor in brains of Tg2576 and controls at the ages of 3, 8, and 14 months...
January 3, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28104309/heightened-cortical-excitability-in-aged-rodents-with-memory-impairment
#4
Rebecca P Haberman, Ming Teng Koh, Michela Gallagher
Elevated excitability in the hippocampus has emerged as a key contributor to reduced memory function in aging and in cognitive impairment prodromal to Alzheimer's disease. Here, we investigated the relationship between neural activity and memory in the hippocampus and a connectional cortical network using an aged rat model of individual differences for memory impairment. The expression of cFos was used as a measure of pharmacologically induced neural activity. Aged memory-impaired rats exhibited elevated cFos relative to young adult and aged unimpaired rats in the CA3 subfield of the hippocampus and in several cortical regions including the retrosplenial, parietal, and orbitofrontal cortices...
January 3, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28110102/transcriptional-profiling-reveals-protective-mechanisms-in-brains-of-long-lived-mice
#5
Christiane Frahm, Akash Srivastava, Silvio Schmidt, Jule Mueller, Marco Groth, Madlen Guenther, Yuanyuan Ji, Steffen Priebe, Matthias Platzer, Otto W Witte
The brain plays a central role in organismal aging but is itself most sensitive to aging-related functional impairments and pathologies. Insights into processes underlying brain aging are the basis to positively impact brain health. Using high-throughput RNA sequencing and quantitative polymerase chain reaction (PCR), we monitored cerebral gene expression in mice throughout their whole lifespan (2, 9, 15, 24, and 30 months). Differentially expressed genes were clustered in 6 characteristic temporal expression profiles, 3 of which revealed a distinct change between 24 and 30 months, the period when most mice die...
December 27, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28104543/a-review-of-human-diseases-caused-or-exacerbated-by-aberrant-complement-activation
#6
REVIEW
Patrick L McGeer, Moonhee Lee, Edith G McGeer
Complement is the backbone of our innate immune system. It is of ancient evolutionary origin, being traced back to horseshoe crabs 350 million years ago. It consists today of more than 25 proteins which must work together like clockwork to distinguish friend from foe. Self-attack by the complement system can occur whenever it fails to do so. This failure has been reported to occur in an estimated 22 human diseases. A significant number of these are chronic degenerative neurological disorders. In some, there is overwhelming evidence that complement self-attack causes the disease...
December 27, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28089352/downregulation-of-mir-132-212-impairs-s-nitrosylation-balance-and-induces-tau-phosphorylation-in-alzheimer-s-disease
#7
Yang Wang, Tatiana Veremeyko, Andus Hon-Kit Wong, Rachid El Fatimy, Zhiyun Wei, Wei Cai, Anna M Krichevsky
MicroRNA-132 is markedly downregulated in Alzheimer's disease (AD) and related tauopathies, and its levels are closely associated with tau pathology in AD. Whether and how miR-132 contributes to pathology in these neurodegenerative diseases remains unclear. Here, we show that miR-132 and its paralogue miR-212 directly regulate the expression of neuronal nitric oxide synthase (NOS1) through the primate-specific binding site. Inhibition of miR-132 in primary human neurons and neural cells leads to increased NOS1 levels and triggers excessive production of nitric oxide, followed by aberrant S-nitrosylation (SNO) of specific proteins associated with neurodegeneration and tau pathology, such as cyclin-dependent kinase 5, dynamin-related protein 1, and glyceraldehyde-3-phosphate dehydrogenase...
December 27, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28094059/alteration-of-methylation-status-in-the-atxn3-gene-promoter-region-is-linked-to-the-sca3-mjd
#8
Chunrong Wang, Huirong Peng, Jiada Li, Dongxue Ding, Zhao Chen, Zhe Long, Yun Peng, Xin Zhou, Wei Ye, Kai Li, Qian Xu, Sanxi Ai, Chengyuan Song, Ling Weng, Rong Qiu, Kun Xia, Beisha Tang, Hong Jiang
DNA methylation has been acknowledged as one of the key epigenetic mechanisms involved in the regulation of gene expression and genomic functions. Alteration of the DNA methylation level has been linked to modification of the disease progression and instability regulation of certain disease-causing repeats in neurodegenerative diseases. In this study, blood samples collected from spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) patients versus control were used to explore the potential link of DNA methylation levels at ATXN3 gene promoter to the pathogenesis of SCA3/MJD...
December 24, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28089353/cerebrospinal-fluid-mitochondrial-dna-in-the-alzheimer-s-disease-continuum
#9
Laura Cervera-Carles, Daniel Alcolea, Ainara Estanga, Mirian Ecay-Torres, Andrea Izagirre, Montserrat Clerigué, Maite García-Sebastián, Jorge Villanúa, Clàudia Escalas, Rafael Blesa, Pablo Martínez-Lage, Alberto Lleó, Juan Fortea, Jordi Clarimón
Low levels of cell-free mitochondrial DNA (mtDNA) in the cerebrospinal fluid (CSF) of Alzheimer's disease (AD) patients have been identified and proposed as a novel biomarker for the disease. The lack of validation studies of previous results prompted us to replicate this finding in a comprehensive series of patients and controls. We applied droplet digital polymerase chain reaction in CSF specimens from 124 patients representing the AD spectrum and 140 neurologically healthy controls. The following preanalytical and analytical parameters were evaluated: the effect of freeze-thaw cycles on mtDNA, the linearity of mtDNA load across serial dilutions, and the mtDNA levels in the diagnostic groups...
December 22, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28104542/hippocampal-morphology-and-cognitive-functions-in-community-dwelling-older-people-the-lothian-birth-cohort-1936
#10
Maria Del Carmen Valdés Hernández, Simon R Cox, Jaeil Kim, Natalie A Royle, Susana Muñoz Maniega, Alan J Gow, Devasuda Anblagan, Mark E Bastin, Jinah Park, John M Starr, Joanna M Wardlaw, Ian J Deary
Structural measures of the hippocampus have been linked to a variety of memory processes and also to broader cognitive abilities. Gross volumetry has been widely used, yet the hippocampus has a complex formation, comprising distinct subfields which may be differentially sensitive to the deleterious effects of age, and to different aspects of cognitive performance. However, a comprehensive analysis of multidomain cognitive associations with hippocampal deformations among a large group of cognitively normal older adults is currently lacking...
December 21, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28089114/genetic-epidemiology-of-motor-neuron-disease-associated-variants-in-the-scottish-population
#11
Holly A Black, Danielle J Leighton, Elaine M Cleary, Elaine Rose, Laura Stephenson, Shuna Colville, David Ross, Jon Warner, Mary Porteous, George H Gorrie, Robert Swingler, David Goldstein, Matthew B Harms, Peter Connick, Suvankar Pal, Timothy J Aitman, Siddharthan Chandran
Genetic understanding of motor neuron disease (MND) has evolved greatly in the past 10 years, including the recent identification of association between MND and variants in TBK1 and NEK1. Our aim was to determine the frequency of pathogenic variants in known MND genes and to assess whether variants in TBK1 and NEK1 contribute to the burden of MND in the Scottish population. SOD1, TARDBP, OPTN, TBK1, and NEK1 were sequenced in 441 cases and 400 controls. In addition to 44 cases known to carry a C9orf72 hexanucleotide repeat expansion, we identified 31 cases and 2 controls that carried a loss-of-function or pathogenic variant...
December 21, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28069311/investigating-the-role-of-als-genes-chchd10-and-tuba4a-in-belgian-ftd-als-spectrum-patients
#12
Federica Perrone, Hung Phuoc Nguyen, Sara Van Mossevelde, Matthieu Moisse, Anne Sieben, Patrick Santens, Jan De Bleecker, Mathieu Vandenbulcke, Sebastiaan Engelborghs, Jonathan Baets, Patrick Cras, Rik Vandenberghe, Peter De Jonghe, Peter P De Deyn, Jean-Jacques Martin, Philip Van Damme, Christine Van Broeckhoven, Julie van der Zee
Mutation screening and phenotypic profiling of 2 amyotrophic lateral sclerosis-(ALS) and frontotemporal dementia-(FTD) associated genes, CHCHD10 and TUBA4A, were performed in a Belgian cohort of 459 FTD, 28 FTD-ALS, and 429 ALS patients. In CHCHD10, we identified a novel nonsense mutation (p.Gln108*) in a patient with atypical clinical FTD and pathology-confirmed Parkinson's disease (1/459, 0.22%) leading to loss of transcript. We further observed 3 previously described missense variants (p.Pro34Ser, p.Pro80Leu, and p...
December 21, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28068565/retinal-thinning-is-uniquely-associated-with-medial-temporal-lobe-atrophy-in-neurologically-normal-older-adults
#13
Kaitlin B Casaletto, Michael E Ward, Nicholas S Baker, Brianne M Bettcher, Jeffrey M Gelfand, Yaqiao Li, Robert Chen, Shubir Dutt, Bruce Miller, Joel H Kramer, Ari J Green
Given the converging pathologic and epidemiologic data indicating a relationship between retinal integrity and neurodegeneration, including Alzheimer's disease (AD), we aimed to determine if retinal structure correlates with medial temporal lobe (MTL) structure and function in neurologically normal older adults. Spectral-domain optical coherence tomography, verbal and visual memory testing, and 3T-magnetic resonance imaging of the brain were performed in 79 neurologically normal adults enrolled in a healthy aging cohort study...
December 21, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28073596/quantitative-eeg-during-normal-aging-association-with-the-alzheimer-s-disease-genetic-risk-variant-in-picalm-gene
#14
Natalya V Ponomareva, Tatiana V Andreeva, Maria S Protasova, Lef I Shagam, Daria D Malina, Andrey Yu Goltsov, Vitaly F Fokin, Sergey N Illarioshkin, Evgeny I Rogaev
Genome-wide association studies have identified novel risk variants for Alzheimer's disease (AD). Among these, a gene carrying one of the highest risks for AD is PICALM. The PICALM rs3851179 A allele is thought to have a protective effect, whereas the G allele appears to confer risk for AD. The influence of the PICALM genotype on brain function in nondemented subjects remains largely unknown. We examined the possible effect of the PICALM rs3851179 genotype on quantitative electroencephalography recording at rest in 137 nondemented volunteers (age range: 20-79 years) subdivided into cohorts of those younger than and those older than 50 years of age...
December 20, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28063365/aging-reduces-the-high-frequency-and-short-term-adaptation-of-the-vestibulo-ocular-reflex-in-mice
#15
Serajul I Khan, Patrick P Hübner, Alan M Brichta, Doug W Smith, Americo A Migliaccio
Prevailing evidence indicates a relatively late life decline in human vestibulo-ocular reflex (VOR) function. Although mice are commonly used in mechanistic studies of vestibular function, it remains unclear whether aging produces a corresponding decline in VOR function in mice. We sought to determine how the baseline VOR and its short-term adaptation were affected by aging. We tested 8 young (3-month old) and 8 aged (30-month old-equivalent to a ∼80-year old human) C57BL/6 mice. We measured their VOR response to whole-body static tilts and during 0...
December 18, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28068564/distinct-patterns-of-increased-translocator-protein-in-posterior-cortical-atrophy-and-amnestic-alzheimer-s-disease
#16
William C Kreisl, Chul Hyoung Lyoo, Jeih-San Liow, Joseph Snow, Emily Page, Kimberly J Jenko, Cheryl L Morse, Sami S Zoghbi, Victor W Pike, R Scott Turner, Robert B Innis
We sought to determine whether patients with posterior cortical atrophy (PCA) demonstrate a pattern of binding to translocator protein 18 kDa, a marker of microglial activation, that is distinct from that in patients with amnestic presentation of Alzheimer's disease (AD). Eleven PCA patients, 11 amnestic AD patients, and 15 age-matched controls underwent positron emission tomography with (11)C-PBR28 to measure translocator protein 18 kDa. PCA patients showed greater (11)C-PBR28 binding than controls in occipital, posterior parietal, and temporal regions...
December 16, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28063366/white-matter-lesions-relate-to-tract-specific-reductions-in-functional-connectivity
#17
Carolyn D Langen, Hazel I Zonneveld, Tonya White, Wyke Huizinga, Lotte G M Cremers, Marius de Groot, Mohammad Arfan Ikram, Wiro J Niessen, Meike W Vernooij
White matter lesions play a role in cognitive decline and dementia. One presumed pathway is through disconnection of functional networks. Little is known about location-specific effects of lesions on functional connectivity. This study examined location-specific effects within anatomically-defined white matter tracts in 1584 participants of the Rotterdam Study, aged 50-95. Tracts were delineated from diffusion magnetic resonance images using probabilistic tractography. Lesions were segmented on fluid-attenuated inversion recovery images...
December 14, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28061384/oligomeric-amyloid-%C3%AE-peptide-disrupts-olfactory-information-output-by-impairment-of-local-inhibitory-circuits-in-rat-olfactory-bulb
#18
Bin Hu, Chi Geng, Xiao-Yu Hou
Although early olfactory dysfunction has been found in patients with Alzheimer's disease, the underlying mechanisms remain unclear. In this study, we investigated whether and how oligomeric amyloid-β peptide (Aβ) affects the responses of mitral cells (MCs). We found that oligomeric Aβ1-42 increased spontaneous and evoked firing rates but decreased the ratio of evoked to spontaneous firings in MCs. Aβ1-42 oligomers showed no impact on the hyperactivity exerted by pharmacological blockage of GABAA receptors, suggesting an involvement of GABAergic inhibitory transmission in Aβ1 to 42-induced over-excitability...
December 14, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28039765/exploring-the-contribution-of-spatial-navigation-to-cognitive-functioning-in-older-adults
#19
Jan Laczó, Ross Andel, Zuzana Nedelska, Martin Vyhnalek, Kamil Vlcek, Sebastian Crutch, John Harrison, Jakub Hort
Spatial navigation (SN) impairment is present early in Alzheimer's disease (AD). We tested whether SN performance, self-centered (egocentric) and world-centered (allocentric), was distinguishable from performance on established cognitive functions-verbal and nonverbal memory, executive and visuospatial function, attention/working memory, and language function. 108 older adults (53 cognitively normal [CN] and 55 with amnestic mild cognitive impairment [aMCI]) underwent neuropsychological examination and real-space navigation testing...
December 14, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28089351/longitudinal-association-between-hippocampus-atrophy-and-episodic-memory-decline
#20
Tetiana Gorbach, Sara Pudas, Anders Lundquist, Greger Orädd, Maria Josefsson, Alireza Salami, Xavier de Luna, Lars Nyberg
There is marked variability in both onset and rate of episodic-memory decline in aging. Structural magnetic resonance imaging studies have revealed that the extent of age-related brain changes varies markedly across individuals. Past studies of whether regional atrophy accounts for episodic-memory decline in aging have yielded inconclusive findings. Here we related 15-year changes in episodic memory to 4-year changes in cortical and subcortical gray matter volume and in white-matter connectivity and lesions...
December 11, 2016: Neurobiology of Aging
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