Abstract：
:Increased mitochondrial hydrogen peroxide (H2O2) is associated with Alzheimer's disease and brain aging. Peroxiredoxin 3 (Prdx3) is the key mitochondrial antioxidant defense enzyme in detoxifying H2O2. To investigate the importance of mitochondrial H2O2 in age-associated cognitive decline, we compared cognition between aged (17-19 months) APP transgenic mice and APP/Prdx3 double transgenic mice (dTG) and between old (24 months) wild-type mice and Prdx3 transgenic mice (TG). Compared with aged APP mice, aged dTG mice showed improved cognition that was correlated with reduced brain amyloid beta levels and decreased amyloid beta production. Old TG mice also showed significantly increased cognitive ability compared with old wild-type mice. Both aged dTG mice and old TG mice had reduced mitochondrial oxidative stress and increased mitochondrial function. Moreover, CREB signaling, a signaling pathway important for cognition was enhanced in both aged dTG mice and old TG mice. Thus, our results indicate that mitochondrial H2O2 is a key culprit of age-associated cognitive impairment, and that a reduction of mitochondrial H2O2 could improve cognition by maintaining mitochondrial health and enhancing CREB signaling.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Chen L,Na R,Ran Qdoi
10.1016/j.neurobiolaging.2014.05.007subject
Has Abstractpub_date
2014-11-01 00:00:00pages
2552-2561issue
11eissn
0197-4580issn
1558-1497pii
S0197-4580(14)00345-5journal_volume
35pub_type
杂志文章abstract：:Aged, cognitively-impaired rats (and humans) show hypothalamic-pituitary-adrenal (HPA) hyperactivity that correlates with hippocampal damage. The resultant increase in plasma glucocorticoid exposure is thought to contribute to impaired hippocampal function and to potentiate hippocampal neuron death. In young, adult ra...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(97)00103-6
更新日期：1997-09-01 00:00:00
abstract：:Although important in neurodegeneration, systematic studies of nicotinic acetylcholine receptor expression in normal aging human brains are difficult to perform. We have studied the expression of nicotinic receptor alpha 4-1 and alpha 5 mRNA in the frontal and parietal isocortex of 3- (young adult), 24- (late middle a...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(97)80316-8
更新日期：1997-05-01 00:00:00
abstract：:Poor cognitive performance of elderly individuals with low educational attainment is often difficult to interpret in dementia evaluation. Lack of education, as well as dementia, is often associated with poor cognitive test performance. To elucidate the underlying structural change of low cognitive performance in elder...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2005.07.020
更新日期：2006-09-01 00:00:00
abstract：:Glial cell line-derived neurotrophic factor (GDNF) supports the viability of midbrain dopamine (DA) neurons that degenerate in Parkinson's disease. Middle-aged, 12 month old, Gdnf heterozygous (Gdnf(+/-)) mice have diminished spontaneous locomotor activity and enhanced synaptosomal DA uptake compared with wild type mi...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.10.013
更新日期：2012-02-01 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：:We evaluated young (3-4 months) and aged (22-24 months) male Sprague-Dawley rats in an attentional set-shifting procedure that assessed reversal, intradimensional shift (IDS), and extradimensional shift (EDS) discrimination learning tasks within one test session. These aspects of discrimination learning are sensitive ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2006.10.005
更新日期：2008-02-01 00:00:00
abstract：:Increasing evidence suggests that cholesterol plays a central role in the pathophysiology of Alzheimer's disease (AD). Caveolin is a cholesterol-binding membrane protein involved in cellular cholesterol transport. We investigated the changes in the protein amount of hippocampal caveolin of autopsy-confirmed AD and age...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2003.07.004
更新日期：2004-07-01 00:00:00
abstract：:The fine structural organization of the floor of the third cerebral ventricle (dorsum of the median eminence of the hypothalamus) of 2 normal adult mice Fisher 344 rats was compared and contrasted with that of 2 aged rats 30 months old. Closely juxtaposed tanycytes (specialized ependymal cells) of normal young adults ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(81)90004-x
更新日期：1981-07-01 00:00:00
abstract：:An association between semicarbazide-sensitive amine oxidase (SSAO) and cerebral amyloid angiopathy (CAA) related to Alzheimer's disease (AD) has been largely postulated. Increased SSAO activity and expression have been detected in cerebrovascular tissue and plasma of AD patients, colocalizing with cerebrovascular amy...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.09.030
更新日期：2015-02-01 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：:Decline in fluid abilities in normal aging is associated with increased white matter lesions, measured on T1-weighted images as white matter signal abnormalities (WMSAs). WMSAs are particularly evident in hypertensive older adults, suggesting vascular involvement. However, because hypertension is assessed systemically...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2019.08.004
更新日期：2019-12-01 00:00:00
abstract：:To determine whether polymorphisms in the microtubule-associated protein tau (MAPT) and/or glycogen synthase kinase-3β (GSK3β) genes underpin susceptibility to Parkinson's disease (PD), we conducted a case-control association study in a Greek cohort of 196 PD cases and 163 healthy controls. In our study, the MAPT H1 h...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2009.05.007
更新日期：2011-03-01 00:00:00
abstract：:Regions of diffuse periventricular white matter hyperintensities (PVWMH) are a common finding on T(2)-weighted MRI scans of older subjects, but their aetiology remains unclear. The aim of this study was to characterize differences in water diffusion and magnetization transfer MRI parameters between macroscopically nor...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2007.05.013
更新日期：2009-01-01 00:00:00
abstract：:We measured midbrain structures of 194 subjects without neurological disorders, using T2-weighted MR imaging. Age was negatively correlated with the maximum anteroposterior distance of the midbrain through the substantia nigra (MD), and the average distance from the substantia nigra to the red nucleus (SNRND), while a...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(01)00227-5
更新日期：2001-07-01 00:00:00
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, t...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2005.03.009
更新日期：2006-04-01 00:00:00
abstract：:The effect of aging on exploratory behavior was investigated in adult (5 month) and aged (28 month) CB6F1 mice. During the first 10 minutes of the test session, aged mice made fewer head dip responses and spent less time exploring the novel stimuli. Because the aged mice were observed to subsequently increase their du...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(81)90021-x
更新日期：1981-10-01 00:00:00
abstract：:We investigated whether individuals with impaired glucose tolerance (IGT) in midlife subsequently show regionally specific longitudinal changes in regional cerebral blood flow (rCBF) relative to those with normal glucose tolerance (NGT). Sixty-four cognitively normal participants in the neuroimaging substudy of the Ba...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.03.025
更新日期：2013-10-01 00:00:00
abstract：:Young, middle-aged, old, and senescent Fischer 344 x Brown Norway F1 hybrid rats were trained in either the trace or delay eyeblink conditioning task in order to investigate how aging affects associative learning and memory over the life span. Senescent rats at 34-35 months showed severe impairments in acquisition of ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(00)00194-9
更新日期：2001-01-01 00:00:00
abstract：:Alzheimer's disease is characterized by amyloid plaques, neurofibrillary tangles, glial activation, and neurodegeneration. In mouse models, inflammatory activation of microglia accelerates tau pathology. The chemokine fractalkine serves as an endogenous neuronal modulator to quell microglial activation. Experiments wi...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2012.12.011
更新日期：2013-06-01 00:00:00
abstract：:Abnormal neuronal excitability and impaired synaptic plasticity might occur before the degeneration and death of neurons in Alzheimer's disease (AD). To elucidate potential biophysical alterations underlying aberrant neuronal network activity in AD, we performed whole-cell patch clamp analyses of L-type (nifedipine-se...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.07.007
更新日期：2014-01-01 00:00:00
abstract：:Counts of neurons in locus coeruleus of Fisher 344 rats of ages from 12 to 32 months showed no loss with advancing age. Species comparisons of age changes in locus coeruleus neuron counts and measures of catecholamine systems suggested that the human and nonhuman primate locus coeruleus shows age changes and seen in r...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(81)90056-7
更新日期：1981-04-01 00:00:00
abstract：:Two neuroanatomically dissociable, large-scale cortical memory networks, referred to as the anterior and posterior medial temporal lobe (MTL) networks have recently been described in young adults using resting-state blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI)-based functional conne...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.03.041
更新日期：2015-01-01 00:00:00
abstract：:We have assessed the frequency of alpha-synuclein (SNCA) mutations in Japanese patients with familial or sporadic Parkinson's disease (PD) and surveyed their associated clinical manifestations. We screened SNCA exon 3 in 988 patients without SNCA multiplications (430 with autosomal dominant PD and 558 with sporadic PD...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2017.05.022
更新日期：2017-09-01 00:00:00
abstract：:Frontotemporal dementias with parkinsonism linked to chromosome 17 (FTDP-17) are hereditary tauopathies affecting at least 50 known kindred worldwide. Most kindred present with severe behavioral or psychiatric manifestations progressing to dementia, while some kindred first manifest a parkinsonian-plus syndrome. Nine ...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/s0197-4580(00)00202-5
更新日期：2001-01-01 00:00:00
abstract：:Age-related synaptic change is associated with the functional decline of the nervous system. It is unknown whether this synaptic change is the cause or the consequence of neuronal cell loss. We have addressed this question by examining mice genetically engineered to over- or underexpress neuregulin-1 (NRG1), a direct ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.05.011
更新日期：2011-12-01 00:00:00
abstract：:Many elderly individuals remain dementia-free throughout their life. However, some of these individuals exhibit Alzheimer disease neuropathology on autopsy, evidenced by neurofibrillary tangles (NFTs) in AD-specific brain regions. We conducted a genome-wide association study to identify genetic mechanisms that disting...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.01.010
更新日期：2011-12-01 00:00:00
abstract：:While cytoskeletal abnormalities are prominent in the neurons of patients with Alzheimer's disease, the possibility remains that these changes are secondary to changes in the neuronal environment. The success of NGF in the therapy of Alzheimer's disease may be dependent on its ability to promote neuronal survival rath...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(89)90134-6
更新日期：1989-09-01 00:00:00
abstract：:The aim of this study was to compare the patterns of grey and white matter atrophy on MRI in autopsy confirmed progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), and to determine whether the patterns vary depending on the clinical syndrome. Voxel-based morphometry was used to compare patterns of...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2006.09.019
更新日期：2008-02-01 00:00:00
abstract：:Repetitive transcranial magnetic stimulation (rTMS), a noninvasive brain stimulation technique, has emerged as a promising treatment for mild cognitive impairment (MCI) and Alzheimer's disease (AD). Currently, however, the effectiveness of this therapy is unclear because of the low statistical power and heterogeneity ...
journal_title：Neurobiology of aging
pub_type： 杂志文章,meta分析
doi：10.1016/j.neurobiolaging.2019.08.020
更新日期：2020-02-01 00:00:00
abstract：:Progranulin (PGRN) mutations account for an average of 15% of familial frontotemporal dementia (FTD) cases and 20% of total FTD cases worldwide. Here, we investigated the frequency of PGRN mutations in FTD patients (n = 116) from a clinical cohort of south India and detected one novel mutation located on exon 12 in a ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2015.11.026
更新日期：2016-03-01 00:00:00
