Abstract：
:Evidence indicates that oxidative stress-induced damage to DNA, protein, and other cellular components contributes to the progression of Alzheimer's disease (AD). Several studies indicate that postmitotic neurons have a reduced capacity for some types of DNA repair, which is further compromised by aging. Thus in AD, the cellular response to increased oxidative DNA damage may be inadequate to protect the genome. Mammalian cells use several mechanisms to repair DNA damage generated during normal oxidative metabolism or by genotoxic insults. The predominant mechanism to repair double strand breaks is non-homologous end joining (NHEJ) which utilizes the DNA-dependent protein kinase (DNA-PK) complex. A cell-free DNA end joining assay was employed to determine if NHEJ was reduced in nuclear cortical extracts from brains of AD versus normal subjects. This report demonstrates that end joining activity and protein levels of DNA-PK catalytic subunit are significantly lower in AD brains compared to normal controls. The amount of end joining activity correlates with the expression of DNA-PK and is dependent on DNA-PK catalytic activity. This indicates that repair of DNA double-strand breaks by the DNA-PK-dependent NHEJ pathway may be deficient in AD.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Shackelford DAdoi
10.1016/j.neurobiolaging.2005.03.009subject
Has Abstractpub_date
2006-04-01 00:00:00pages
596-605issue
4eissn
0197-4580issn
1558-1497pii
S0197-4580(05)00106-5journal_volume
27pub_type
杂志文章abstract：:Rats with electrolytic lesions of the medial septum or ibotenic acid lesions of the nucleus basalis magnocellularis (NBM) were tested in an order memory task for an 8-item list of varying spatial locations within an 8-arm radial maze. Results indicated that rats with small medial septal lesions resulting in small AchE...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(86)90009-6
更新日期：1986-07-01 00:00:00
abstract：:We have shown previously that the TG-3 and MPM-2 antibodies recognize phosphoepitopes common to mitosis and degenerating neurons of Alzheimer's disease(AD) brain. Here, we have evaluated their occurrence in human brain biopsy tissue, and confirm that they are absent in mature neurons of adult brain, but reappear durin...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(98)00071-2
更新日期：1998-07-01 00:00:00
abstract：:Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurotrophin. However, its role in human Alzheimer's disease (AD) is largely unknown. We examined PACAP expression in postmortem human AD and triple transgenic mouse (3xTG, Psen1/APPSwe/TauP301L) brains. We established an in vitro model of primary neurona...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.03.022
更新日期：2014-09-01 00:00:00
abstract：:Mimicking relevant behavioral features of the human pathology is one of the most important challenges for animal models of neurological disorders including Alzheimer disease (AD). Indeed, the most popular genetic AD mouse lines bearing mutations of the amyloid precursor protein (APP) and presenilin 1 genes (PS1), ofte...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.09.012
更新日期：2012-05-01 00:00:00
abstract：:An extensive literature reports changes in quantitative electroencephalogram (QEEG) with aging and a relationship between magnitude of changes and degree of clinical deterioration in progressive dementia. Longitudinal studies have demonstrated QEEG differences between mild cognitively impaired (MCI) elderly who go on ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2005.07.021
更新日期：2006-03-01 00:00:00
abstract：:Support has recently been voiced for the genetic hypothesis of Alzheimer's disease; frequently at the expense of considerations of environmental factors. In the adult, genetic diseases rarely exist without modification by environment forces. Atherosclerosis leading to myocardial infarction may provide a useful model t...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(89)90093-6
更新日期：1989-09-01 00:00:00
abstract：:Degeneration of septal neurons in Alzheimer's disease (AD) results in abnormal information processing at cortical circuits and consequent brain dysfunction. The septum modulates the activity of hippocampal and cortical circuits and is crucial to the initiation and occurrence of oscillatory activities such as the hippo...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2008.05.006
更新日期：2010-01-01 00:00:00
abstract：:Long-term dietary supplementation with resveratrol protects against cardiovascular disease, osteoporesis, and metabolic decline. This study determined how long-term dietary resveratrol treatment protects against retinal ganglion cell (RGC) dendrite loss after optic nerve injury and alters the resolution of the unfolde...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.12.021
更新日期：2015-05-01 00:00:00
abstract：:The social species Octodon degus (degu) is the only wild-type South American rodent that develops Alzheimer's-like pathology with age. Here, we evaluated the ability of a natural product (Andrographolide, ANDRO), a diterpene of the labdane family obtained from the Asian plant Andrographis paniculata, to recover the co...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.06.021
更新日期：2016-10-01 00:00:00
abstract：:Oxidative stress is considered to be a major contributor to age-related hearing loss (ARHL). Here, we investigated whether pomegranate peel extract (PPE) protected against hearing loss by decreased oxidative stress in the cochlea of D-galactose-induced accelerated aging mice. The aging mice exhibited an increase in he...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2017.07.007
更新日期：2017-11-01 00:00:00
abstract：:Compared to young rats, old age increases susceptibility and caloric restriction decreases susceptibility for the loss of retinal ganglion cells and displaced amacrine cells following retinal ischemia/reperfusion. In retinas of old animals before ischemia, reactive gliosis, including activation of Muller cells, microg...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2003.07.005
更新日期：2004-04-01 00:00:00
abstract：:Neuropeptide Y (NPY) has been implicated in the control of reproductive and cardiovascular function. We observed an age-related decrease in the number of males copulating to ejaculation and a moderate systolic hypertension in middle-aged (16- to 17-month-old) rats. NPY content was examined in microdissected brain nucl...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(94)90111-2
更新日期：1994-03-01 00:00:00
abstract：:N-Methyl-D-Aspartate (NMDA) receptors are believed to play a critical role in excitotoxic cell death in the CNS. The distribution of NMDA-preferring binding sites is compared here with the patterns of selective neuronal death observed in Alzheimer's disease and following transient ischemia. The distribution of NMDA re...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(89)90148-6
更新日期：1989-09-01 00:00:00
abstract：:The observation that neurons containing neurofibrillary tangles are usually adjacent to neurons free of any morphological indication of disease, suggests the hypothesis that it is NFT-bearing neurons that are primarily responsible for the loss of function in AD. Quantitative Golgi postmortem studies from our laborator...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(95)00035-d
更新日期：1995-05-01 00:00:00
abstract：:Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by loss of motor neurons. We have recently identified SOD1 and FUS mutations as the most common causes in a consecutive series of 111 familial ALS pedigrees in Japan. To reveal possible genetic causes for the remaining 51 pat...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2017.01.004
更新日期：2017-05-01 00:00:00
abstract：:The three chapters on the use of classical conditioning paradigms to investigate neurobiological and behavioral substrates of memory impairments with aging are in close agreement on all key issues. Based on these chapters, it is argued here that classical conditioning of discrete behavioral responses in rabbit and oth...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(88)80111-8
更新日期：1988-09-01 00:00:00
abstract：:Magnetic resonance (MR)-based volume measurements of atrophy are potential markers of disease progression in patients with amnestic mild cognitive impairment (MCI) and Alzheimer's disease (AD). Longitudinal changes in (1)H MR spectroscopy ((1)H MRS) metabolite markers have not been characterized in MCI subjects. Our o...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2006.06.018
更新日期：2007-09-01 00:00:00
abstract：:Possession of an Apolipoprotein E (APOE) e4 allele is an established risk factor for Alzheimer's disease, whereas the less commonly studied e2 variant is premised to offer some protection. This research explores the purported deleterious-protective dichotomy of APOE variants on attentional control in mid-adulthood. Si...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.08.015
更新日期：2016-12-01 00:00:00
abstract：:Neuronal alphabeta heteromeric and alpha7 homomeric nicotinic acetylcholine receptors (nAChRs) were compared in 4- and 27-month rabbits selected for learning proficiency. Sixty 4- and 60 27-month rabbits received the alpha7 nAChR agonist (MEM-3389), galantamine, or vehicle during training in trace eyeblink classical c...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2008.09.002
更新日期：2010-06-01 00:00:00
abstract：:Significant advances in the technology for the isolation of peptides and small proteins have permitted their identification as biologic markers and enhanced the study of the posttranslational life of proteins. The protocol described here examined large numbers of tissue-derived peptides and small proteins, extracted i...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(92)90087-e
更新日期：1992-11-01 00:00:00
abstract：:Alzheimer's disease (AD) is characterized by the presence of β-amyloid (Aβ) deposition and neurodegeneration. To seek for signs of such pathologies, we compared regional biomarker degrees and patterns of Aβ deposition, glucose hypometabolism, and gray matter volume (GMV) reduction in 3 groups at risk of AD. In elderly...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2017.10.023
更新日期：2018-03-01 00:00:00
abstract：:Aging-related episodic memory decline is often attributed to insufficient encoding of new information, although the underlying neural processes remain elusive. We here tested the hypothesis that impaired memory consolidation contributes to aging-related memory decline. To this end, we used resting state functional mag...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.06.004
更新日期：2016-09-01 00:00:00
abstract：:To better understand the role of insulin signaling in the development of Alzheimer's disease (AD), we utilized an animal model (intracerebroventricular injection of streptozotocin-ic-streptozotocin (STZ)) that displays insulin resistance only in the brain and exhibits AD pathology. In this model, deficits in hippocamp...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.12.002
更新日期：2012-02-01 00:00:00
abstract：:The study aimed to evaluate the effects of noninvasive brain stimulation on cognitive function in healthy older adults and patients with Alzheimer's disease. A comprehensive literature search was performed on noninvasive stimulation studies published from January 1990 to November 2014 in Pubmed and Web of Science. Fou...
journal_title：Neurobiology of aging
pub_type： 杂志文章,meta分析,评审
doi：10.1016/j.neurobiolaging.2015.04.016
更新日期：2015-08-01 00:00:00
abstract：:Cholesterol has been implicated in the pathogenesis of late-onset Alzheimer's disease (LOAD) and the cholesteryl ester transfer protein (CETP) is critical to cholesterol regulation within the cell, making CETP an Alzheimer's disease candidate gene. Several studies have suggested that CETP I405V (rs5882) is associated ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.08.022
更新日期：2015-01-01 00:00:00
abstract：:The current study describes both Abeta and tau abnormalities that accumulate in the brains of aged (16-21 years), but not young (<4 years) clinically characterized cats. Diffuse plaques that were morphologically different from what is typically observed in the human brain could be detected with 4G8 (Abeta17-24) or an ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2004.06.015
更新日期：2005-05-01 00:00:00
abstract：:In Alzheimer's disease, there is a major redistribution of the tau protein pool from soluble to PHF-bound forms. PHF-bound tau can be distinguished from normal tau by acid reversible occlusion of a generic tau epitope in the tandem repeat region and characteristic sedimentation in the if-II protocol developed in this ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(95)97327-d
更新日期：1995-05-01 00:00:00
abstract：:The neuropeptide neurokinin 3 (NK3) and its receptor modulate cholinergic activity of the basal forebrain (BF) and are implicated in learning and memory. In Alzheimer's disease, the rs2765 single-nucleotide polymorphism (SNP) of the NK3 receptor-coding gene TACR3 was correlated with the right hippocampus volume. Here,...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.12.031
更新日期：2015-06-01 00:00:00
abstract：:It was previously reported that in soleus neuromuscular junctions of old mice, synaptic vesicle density was decreased while transmitter release was increased (compared to results in young mice). In the present study, two hypotheses that might resolve this disparity were tested. The first was that the density of readil...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(87)90061-3
更新日期：1987-01-01 00:00:00
abstract：:Previously, we demonstrated that plasticity of frontal cortex is altered in aging rats: 3 months after surgery, excitotoxic lesions of the nucleus basalis magnocellularis (NBM) produce larger declines in dendritic morphology in frontal cortex of aged rats relative to young adults. To determine whether the differential...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2003.08.003
更新日期：2004-08-01 00:00:00
