Abstract：
:Mutations in fused in sarcoma (Fus) cause familial amyotrophic lateral sclerosis (ALS) and occasionally frontotemporal dementia. Here we report the establishment and characterization of a novel knockin (KI) rat model expressing a Fus point mutation (R521C) via CRISPR/Cas9. The mutant animals developed adult-onset learning and memory behavioral deficits, with reduced spine density in hippocampal neurons. Remarkably, sleep-wake cycle and circadian abnormalities preceded the onset of cognitive deficit. RNA-seq study further demonstrated altered expression of some key sleep and circadian regulators, such as orexin/hypocretin receptor type 2 and casein kinase 1 epsilon, in the mutant rats. Therefore, we have established a rodent model expressing physiological level of a pathogenic mutant FUS, and we found cognitive impairment as a main behavioral deficit at mid age. Furthermore, we have revealed a new role of FUS in sleep and circadian regulation and demonstrated that functional change in FUS could cause sleep-wake and circadian disturbance as early symptoms.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Zhang T,Jiang X,Xu M,Wang H,Sang X,Qin M,Bao P,Wang R,Zhang C,Lu H,Li Y,Ren J,Chang HC,Yan J,Sun Q,Xu Jdoi
10.1016/j.neurobiolaging.2018.08.025subject
Has Abstractpub_date
2018-12-01 00:00:00pages
159-170eissn
0197-4580issn
1558-1497pii
S0197-4580(18)30316-6journal_volume
72pub_type
杂志文章abstract：:The triple transgenic mouse model (3×TgAD: APPswe, TauP301L, PS1M146V) recapitulates both amyloid β (Aβ)- and tau-related lesions as well as synaptic and memory deficits. In these mice, we reported an early apathy-like behavior and alterations in synaptic plasticity appearing concomitantly with intraneuronal accumulat...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2018.06.038
更新日期：2018-11-01 00:00:00
abstract：:Posterior cortical atrophy (PCA) is an understudied visual impairment syndrome most often due to "posterior Alzheimer's disease (AD)" pathology. Case studies detected mutations in PSEN1, PSEN2, GRN, MAPT, and PRNP in subjects with clinical PCA. To detect the frequency and spectrum of mutations in known dementia genes ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2015.09.023
更新日期：2016-01-01 00:00:00
abstract：:In order to investigate inflammation and apoptosis in Creutzfeldt-Jakob disease (CJD) patients, we analyzed astrocytes, microglia and apoptotic neurons in brain and IL-1beta in cerebrospinal fluid (CSF). Our results showed increased numbers of astrocytes in CJD and increased numbers of microglia and apoptotic neurons ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(01)00236-6
更新日期：2002-01-01 00:00:00
abstract：:Humans carrying the prevalent rs9939609 A allele of the fat mass and obesity-associated (FTO) gene are more susceptible to developing obesity than noncarries. Recently, polymorphisms in the FTO gene of elderly subjects have also been linked to a reduced volume in the frontal lobe as well as increased risk for incident...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.02.006
更新日期：2011-06-01 00:00:00
abstract：:Activated astrocytes have been identified as the main source of the serine protease inhibitor alpha 1-antichymotrypsin (ACT), an acute phase protein that is tightly associated with amyloid plaques in Alzheimer's disease (AD) and in normal aged human and monkey brain. We analyzed the synthesis of ACT by cultured murine...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(96)00111-x
更新日期：1996-09-01 00:00:00
abstract：:We sought to examine the relations between age, gender and brain volumes in an elderly population; we also sought to examine ways of measuring these relations. Three sets of analyses were used: correlational analyses, in which correlations between independent variables and brain volumes were calculated without correct...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2006.09.016
更新日期：2008-02-01 00:00:00
abstract：:Association of the A2 allele of the human leukocyte antigen (HLA) with Alzheimer disease (AD) is still controversial. The authors evaluated HLA-A2 association with AD in 173 Italian AD patients, considering also the possible interaction with APOE pattern, age of onset and gender. No evidence of any association was fou...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2008.02.001
更新日期：2009-12-01 00:00:00
abstract：:Healthy aging is associated with declines in episodic memory performance that are due in part to deficits in encoding. Emerging results from young adult studies suggest that the neural activity during the time preceding stimulus presentation is sensitive to episodic memory performance. It is unknown whether age-relate...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2019.01.005
更新日期：2019-05-01 00:00:00
abstract：:The vervet is an old world monkey increasingly being used as a model for human diseases. In addition to plaques and tangles, an additional hallmark of Alzheimer's disease is damage to neurons that synthesize noradrenaline (NA). We characterized amyloid burden in the posterior temporal lobe of young and aged vervets, a...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.03.023
更新日期：2013-10-01 00:00:00
abstract：:Aging is associated with marked changes in the timing, consolidation and structure of sleep. Older people wake up frequently, get up earlier and have less slow wave sleep than young people, although the extent of these age-related changes differs considerably between individuals. Interindividual differences in homeost...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.10.024
更新日期：2012-05-01 00:00:00
abstract：:Middle-aged and aged rats received dorsal hippocampal lesions before performance was evaluated on the radial-arm maze. The maze task contained simultaneous spatial working memory and visually cued reference memory components. Both middle-aged and aged rats that received lesions committed more errors of both types than...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(99)00047-0
更新日期：1999-07-01 00:00:00
abstract：:Alzheimer's disease (AD) is a devastating age-related neurodegenerative disease with no specific treatment at present. Several healthy lifestyle options and over-the-counter drugs that it has been suggested delay the onset of the disease are in an experimental phase, but it is unclear whether they will have any therap...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.11.016
更新日期：2012-06-01 00:00:00
abstract：:In the present study, the effects of long-term dietary restriction (60% of the calories in the ad lib diet, beginning at 16 weeks of age) on quantitative morphometric measures and histopathologic indications of aging have been investigated in the retina of Fischer 344 male rats. The animals were maintained by the NIA ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(91)90073-s
更新日期：1991-09-01 00:00:00
abstract：:Chronic circadian disturbance, a condition of desynchronization between endogenous clock and environmental light-dark (LD) cycle, is known to cause adverse physiological changes including mortality. However, it is yet unclear whether these consequences result from disturbance of endogenous clock or condition of the LD...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.11.005
更新日期：2012-06-01 00:00:00
abstract：:Synaptic density in the medial and lateral septal nuclei was examined in 3 and 24-28 months of age Fischer 344 rats. The lateral nucleus had a higher synaptic density than the medial region in both age groups. There were no statistically significant differences in synapse density in either region as a function of age,...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/0197-4580(91)90032-f
更新日期：1991-01-01 00:00:00
abstract：:Mitophagy and mitochondrial biogenesis are 2 pathways that regulate mitochondrial content and metabolism maintaining cellular homeostasis. The imbalance between these opposing processes impairs mitochondrial function and is suggested to be the pathophysiological basis of a variety of neurodegenerative diseases and agi...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2019.03.013
更新日期：2019-07-01 00:00:00
abstract：:The aim of this study was to estimate the number of new cells and neurons added to the dentate gyrus across the lifespan, and to compare the rate of age-associated decline in neurogenesis across species. Data from mice (Mus musculus), rats (Rattus norvegicus), lesser hedgehog tenrecs (Echinops telfairi), macaques (Mac...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.03.008
更新日期：2012-08-01 00:00:00
abstract：:G4C2 hexanucleotide repeat expansions in the C9orf72 gene seem to be the cause of numerous cases of amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD). In this study, we investigated the presence of the G4C2 repeat expansion in 463 Brazilian probands, of whom 404 had ALS/motor neuron disease and ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2018.01.007
更新日期：2018-06-01 00:00:00
abstract：:We have previously shown beneficial effects of a Ginkgo biloba extract (EGb761-IPSEN) in accelerating functional recovery from hemiplegia induced by unilateral motor cortex ablation. Here, we report the behavioral and histological effects of various dose regimes of EGb761. In young rats (3 months), 10 mg/kg/day for 7 ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(97)00007-9
更新日期：1997-03-01 00:00:00
abstract：:Oxidative stress has been linked to noise- and drug-induced as well as age-related hearing loss. Antioxidants can attenuate the decline of cochlear structure and function after exposure to noise or drugs, but it is debated as to whether they can protect from age-related hearing loss. In a long-term longitudinal study,...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.10.023
更新日期：2012-05-01 00:00:00
abstract：:Dynamic changes in the brain's lateral ventricles on magnetic resonance imaging are powerful biomarkers of disease progression in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Ventricular measures can represent accumulation of diffuse brain atrophy with very high effect sizes. Despite having no direct ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.03.044
更新日期：2015-01-01 00:00:00
abstract：:Chronic hypertension during aging is a serious threat to the cerebral vasculature. The larger brain arteries can react to hypertension with an abnormal wall thickening, a loss of elasticity and a narrowed lumen. However, little is known about the hypertension-induced alterations of cerebral capillaries. The present st...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(00)00225-6
更新日期：2001-03-01 00:00:00
abstract：:Apolipoprotein E (ApoE) ε4 is known as a genetic risk factor for Alzheimer's disease (AD). This study investigated the prevalence of imaging abnormalities suggestive of AD in cognitively normal ApoE ε4 carriers using (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and voxel-based morphometry (VBM). F...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.11.020
更新日期：2012-10-01 00:00:00
abstract：:Alzheimer's disease (AD) is the most common dementia among the elderly that involves complex neurodegenerative alterations. Multiple cellular processes including regulation of amyloid-β peptide, tau, inflammation, and cell death have been suggested to associate with AD, but it remains largely unknown if long noncoding...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2015.07.015
更新日期：2015-11-01 00:00:00
abstract：:It is unknown whether lifestyle, including mental stimulation, and appropriate training interventions, may directly improve spatial navigation performance and its underlying neural substrates. Here we report that healthy younger and older men performing a cognitively demanding spatial navigation task every other day o...
journal_title：Neurobiology of aging
pub_type： 临床试验,杂志文章
doi：10.1016/j.neurobiolaging.2011.02.013
更新日期：2012-03-01 00:00:00
abstract：:Brain iron promotes neurodegeneration in Parkinson's disease (PD). While hemoglobin (Hb) is the most abundant source of peripheral iron in humans, its relationship with PD is uncertain. This report examines the association between Hb in late life and PD incidence. From 1991 to 1993, Hb was measured in 3507 men in the ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.06.023
更新日期：2012-05-01 00:00:00
abstract：:Activated microglia are instrumental to neurodegeneration in Parkinson's disease (PD). Fractalkine, as an exclusive ligand for CX3CR1 expressed on microglia, has recently been reported to be released out by neurons, and induce microglial activation as a neuron-to-glia signal in the spinal cord. However, the role of fr...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2009.03.004
更新日期：2011-03-01 00:00:00
abstract：OBJECTIVE:We used positron emission tomography to evaluate cerebral glucose metabolic change in postmenopausal women in a naturalistic observational study. METHOD:Women estrogen users (n = 11) and non-users (n = 9) were studied at baseline and 2 years later. Analyses focused on glucose metabolism in regions previously...
journal_title：Neurobiology of aging
pub_type： 临床试验,杂志文章
doi：10.1016/j.neurobiolaging.2004.03.003
更新日期：2005-02-01 00:00:00
abstract：:The levels of calpains (m-calpain and mu-calpain) in peripheral blood lymphocytes from patients with Alzheimer's disease were determined via Western blotting. The Ca-dependent proteolytic activity and the calpastatin activity were estimated using incubation with exogenous substrate. Evidence was obtained for an increa...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(95)02004-7
更新日期：1995-11-01 00:00:00
abstract：:Decreases in the activity or density of dopamine D2 receptor (D2R) have been associated with age-related changes and neurodegenerative diseases such as Parkinson's disease. There are two isoforms of the D2R, termed the D2 long receptor (D2LR) and D2 short receptor (D2SR). To study the function of these two isoforms an...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2004.04.005
更新日期：2005-04-01 00:00:00
