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 and their role in aging, we generated mice selectively lacking D2LR (D2L-/-). Here, we showed that middle-aged (12 months) to aged wild-type (WT) mice (22-24 months) displayed significantly lower levels of motor and learning functions than young WT mice (3 months). Interestingly, young D2L-/- mice (which still express D2SR) showed behavioral deficits similar to aged WT mice. It is possible that deletion of the D2LR might facilitate the aging process in mice. Our results also suggest that a deterioration of the D2LR (but not D2SR) system during aging may account, at least in part, for the motor and learning deficits exhibited in aged WT mice. We also showed that the critical age at which significant reduction in behavior occurred varied among different behaviors. Defining the age-related critical periods and understanding the role of the two D2R isoforms in aging may facilitate the development of new strategies for delaying or ameliorating age-related motor and learning impairments.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Fetsko LA,Xu R,Wang Ydoi
10.1016/j.neurobiolaging.2004.04.005subject
Has Abstractpub_date
2005-04-01 00:00:00pages
521-30issue
4eissn
0197-4580issn
1558-1497pii
S0197458004001666journal_volume
26pub_type
杂志文章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：PURPOSE:The goal of this project was to compare MRI measures of hippocampal, entorhinal cortex (ERC), and whole brain longitudinal change in cognitively normal elderly controls (C), non-demented subjects with cognitive impairment (CI), and demented (D) subjects. METHODS:16 C, 6 CI, and 7 D subjects of comparable age w...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(02)00130-6
更新日期：2003-07-01 00:00:00
abstract：:Clinico-pathological studies reveal that some elderly people with no cognitive impairment have high burdens of neurofibrillary tangles (NFTs), a pathology associated with Alzheimer's disease. We examined a total of 123 elderly participants without dementia and free of other neurological disorders or pathologies who at...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2015.10.012
更新日期：2016-01-01 00:00:00
abstract：:The present study assessed whether there are age-dependent differences in up-regulation of opiate receptors following chronic naloxone treatment in mature (3 months) and aged (27 months) male Wistar rats. Half of each age group were implanted subdermally with slow-release naloxone pellets for 10 days, and half were gi...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(89)80011-9
更新日期：1989-01-01 00:00:00
abstract：:Long-term ovariectomy attenuates several neuroendocrine-dependent changes in reproductive function of aging female rodents, but the sites affected and underlying mechanisms are not known. This study was designed to identify effects of aging on hypothalamic-preoptic neurocytoarchitecture and to determine whether long-t...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(89)90005-5
更新日期：1989-11-01 00:00:00
abstract：:The available published guidelines for the housing of rodents are reviewed, and assessments are made with regard to whether the data on which these guidelines are based appear to be sound. Ambient air temperature, relative humidity, lighting levels and photoperiods, sound levels, cage sizes, and ventilation rates are ...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/0197-4580(91)90116-2
更新日期：1991-11-01 00:00:00
abstract：:Alzheimer's disease (AD) involves progressive neurodegeneration in the presence of misfolded proteins and poorly-understood inflammatory changes. However, research has shown that AD is genetically, clinically, and pathologically heterogeneous. In frozen brain samples of frontal cortex (diseased) and cerebellum (nondis...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2012.09.012
更新日期：2013-04-01 00:00:00
abstract：:TREM2 mutations were first identified in Nasu-Hakola disease, a rare autosomal recessive disease characterized by recurrent fractures because of bone cysts and presenile dementia. Recently, homozygous and compound heterozygous TREM2 mutations were identified in rare families with frontotemporal lobar degeneration (FTL...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.04.010
更新日期：2014-10-01 00:00:00
abstract：:Dysfunction of circadian melatonin production by the pineal gland in aged humans and rats is thought to reflect the functional loss of its sympathetic innervation. Our ultrastructural neuropathologic studies of the sympathetic innervation of the pineal gland of aged (24 months old) Fischer-344 and Sprague-Dawley rats ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2005.08.005
更新日期：2006-10-01 00:00:00
abstract：:Alterations in the buffering capacity of the proteostasis network are a salient feature of Alzheimer's disease, associated with the occurrence of chronic endoplasmic reticulum (ER) stress. To cope with ER stress, cells activate the unfolded protein response (UPR), a signal transduction pathway that enforces adaptive p...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/j.neurobiolaging.2017.09.012
更新日期：2018-03-01 00:00:00
abstract：:An individual's genetic makeup plays an important role in determining susceptibility to cognitive aging. Identifying the specific genes that contribute to cognitive aging may aid in early diagnosis of at-risk patients, as well as identify novel therapeutics targets to treat or prevent development of symptoms. Challeng...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.06.008
更新日期：2016-10-01 00:00:00
abstract：:In amyotrophic lateral sclerosis (ALS), objective biomarkers are needed for early diagnosis and progression monitoring. Reduced phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) has recently been proposed to provide such a biomarker in ALS. Here, we aimed to scrutinize this notion, evaluating both p-tau and tota...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.10.019
更新日期：2015-02-01 00:00:00
abstract：:Sleep benefits memory across a range of tasks for young adults. However, remarkably little is known of the role of sleep on memory for healthy older adults. We used 2 tasks, 1 assaying motor skill learning and the other assaying nonmotor/declarative learning, to examine off-line changes in performance in young (20-34 ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.06.029
更新日期：2012-05-01 00:00:00
abstract：:This study aimed to investigate cross-sectional and longitudinal changes of regional cerebral blood flow (rCBF) in preclinical dementia using single photon emission computed tomography (SPECT). SPECT and cognitive function were investigated in 39 mild cognitive impairment (MCI) subjects and 20 age-matched controls. Al...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2006.05.017
更新日期：2007-07-01 00:00:00
abstract：:Cerebral gray-matter volume (GMV) decreases in normal aging but the extent of the decrease may be experience-dependent. Bilingualism may be one protective factor and in this article we examine its potential protective effect on GMV in a region that shows strong age-related decreases-the left anterior temporal pole. Th...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.03.010
更新日期：2014-09-01 00:00:00
abstract：:We examined the interaction of brain atrophy and white matter lesions (WML) with cognitive functioning in 605 patients (mean age, 58±10; 76% men) with atherosclerotic disease from the Second Manifestations of ARTerial disease-MR substudy (SMART-MR study). Automated brain segmentation was used to quantify volumes of br...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2009.05.005
更新日期：2011-05-01 00:00:00
abstract：:Results from basic and clinical studies demonstrate that stress and depression decrease neurotrophic factor expression and neurogenesis in brain, and that antidepressant treatment blocks or reverses these effects, leading to a neurotrophic hypothesis of depression. Neurotrophic factor expression and neurogenesis are a...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/j.neurobiolaging.2005.08.018
更新日期：2005-12-01 00:00:00
abstract：:Medial temporal lobe atrophy (MTA) and cerebrospinal fluid (CSF) markers of Alzheimer's disease (AD) pathology may aid the early detection of AD in mild cognitive impairment (MCI). However, the relationship between structural and pathological markers is not well understood. Furthermore, while posterior atrophy (PA) is...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2012.03.010
更新日期：2013-01-01 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：:Genetics is intricately involved in the etiology of neurodegenerative dementias. The incidence of monogenic dementia among all neurodegenerative forms is unknown due to the lack of systematic studies and of patient/clinician access to extensive diagnostic procedures. In this study, we conducted targeted sequencing in ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2018.02.006
更新日期：2018-06-01 00:00:00
abstract：:We report that a peripheral injection of Escherichia coli produces both anterograde and retrograde amnesia in 24 month old, but not 3 month old rats for memories that depend on the hippocampus, that is, memory of context, contextual fear, and place learning. The anterograde effect was restricted to measures of long-te...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2005.03.010
更新日期：2006-05-01 00:00:00
abstract：:Linkage data in Alzheimer's disease have not firmly established a genetic locus on chromosome 21 in early onset disease families. There is little or no support for a chromosome 21 locus in late onset families. Differences in the selection of families and the analysis of data accounts for the differences in interpretat...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(89)90083-3
更新日期：1989-09-01 00:00:00
abstract：:We obtained serum samples and measured alpha 1-antichymotrypsin (ACT) levels in 36 pairs of consecutive probable Alzheimer's disease (AD) patients and age- and sex-matched, cognitively intact control subjects. Serum ACT was measured by radial immunodiffusion. Unique to this study, we found that ACT levels rose signifi...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(94)90141-4
更新日期：1994-01-01 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：:Alzheimer's disease (AD) is the most common cause of dementia and, despite decades of effort, there is no effective treatment. In the last decade, many association studies have identified genetic markers that are associated with AD status. Two of these studies suggest that an epistatic interaction between variants rs1...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2020.01.013
更新日期：2020-05-01 00:00:00
abstract：:In the present study, we aim at investigating whether education modulates dynamical properties of time-varying whole-brain network connectivity (the chronnectome) in frontotemporal dementia (FTD) at a given level of symptom severity. Dynamic connectivity parameters were evaluated in 128 patients with FTD using indepen...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2020.04.021
更新日期：2020-09-01 00:00:00
abstract：:The 3-dimensional (3-D) distribution of cholinergic neurons located throughout the extent of the entire basal forebrain of young (4-5 months old) and aged (24-25 months old) Fischer-344 rats was examined using choline acetyltransferase immunocytochemistry (ChAT-IR). The number and 3-D position of ChAT-IR neurons spann...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(93)90126-v
更新日期：1993-07-01 00:00:00
abstract：:CR1 is a novel Alzheimer's disease (AD) gene identified by genome-wide association studies (GWAS). Recently, we showed that AD risk could be explained by an 18-kilobase insertion responsible for the complement component (3b/4b) receptor 1 (CR1)-S isoform. We investigated the relevance of the CR1 isoforms to AD in a Ca...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2012.07.001
更新日期：2012-12-01 00:00:00
abstract：:In attempts to understand the diverse roles which trophic activities exert in neuronal development and maintenance, it is useful to define some framework from within which to view their function. An example of such an outline is presented, sufficiently broad to avoid excluding by definition agents with clearly neurotr...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(89)90120-6
更新日期：1989-09-01 00:00:00
abstract：:Age-related decline in microstructural integrity of certain white matter tracts may explain cognitive decline associated with normal aging. Whole brain tractography and a clustering segmentation in 48 healthy individuals across the adult lifespan were used to examine: interhemispheric (corpus callosum), intrahemispher...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.02.009
更新日期：2012-01-01 00:00:00
