Abstract：
:A promising intervention for Alzheimer's disease (AD) would ideally target key pathological factors that are involved in AD pathogenesis. Soluble factors produced by engrafted mesenchymal stem cells (MSCs) mediate potential therapeutic effects in AD. However, these therapeutic benefits are largely hampered by the limited paracrine capacity of MSCs. In this study, we used adenovirus-mediated gene transduction of bone marrow MSCs to deliver exogenous proteins into the brain of APPswe/PSEN1dE9 (APP/PS1) mice in the early stage of impairment. We observed that engrafted MSCs carrying exogenous (C-X3-C motif) ligand 1 (CX3CL1) alone reduced the production of the inflammatory cytokine TNF-ɑ and improved synapse-related protein expression but not cognitive function. Transplantation of MSCs carrying CX3CL1 and Wnt3a (CX3CL1-Wnt3a-MSC) significantly attenuated the learning and memory impairment when compared with a control group. The improvement of neurobehavioral functions in APP/PS1 mice treated with CX3CL1-Wnt3a-MSC was related to the inhibition of microglial neurotoxicity and promotion of hippocampal neurogenesis. Transplantation of CX3CL1-Wnt3a-MSC also regulated phosphoinositide 3-kinase/activated protein kinase B (PI3K/AKT) signaling to inhibit the activity of glycogen synthase kinase 3 beta (GSK3β). Taken together, these results indicate that the delivery of exogenous proteins via MSCs can modulate microglial function and enhance neurogenesis, thereby providing new insights into AD intervention.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Li A,Zhao J,Fan C,Zhu L,Huang C,Li Q,Gan D,Wen C,Chen M,Lu Ddoi
10.1016/j.neurobiolaging.2019.10.012subject
Has Abstractpub_date
2020-02-01 00:00:00pages
81-91eissn
0197-4580issn
1558-1497pii
S0197-4580(19)30375-6journal_volume
86pub_type
杂志文章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 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：:We sought to describe change in cardiorespiratory (CR) fitness over 2 years in those with early-stage Alzheimer's disease (AD) and nondemented aging and assess the relationship of CR fitness with cognitive decline, brain atrophy, and dementia progression. Individuals with early-stage AD (n = 37) and without dementia (...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.03.016
更新日期：2012-08-01 00:00:00
abstract：:Mutants of presenilin 1 (PS1) increase neuronal cell death causing autosomal-dominant familial Alzheimer's disease (FAD). Recent literature shows that treatment of neuronal cultures with low concentrations of trypsin, a member of the serine family of proteases, protects neurons from toxic insults by binding to the pro...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.02.028
更新日期：2016-06-01 00:00:00
abstract：:Arrested autophagy may contribute to the pathogenesis of Alzheimer's disease. Because we found that chloroquine (CQ) causes arrested autophagy but clioquinol (ClioQ), a zinc ionophore, activates autophagic flux, in the present study, we examined whether ClioQ can overcome arrested autophagy induced by CQ or mutant pre...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2015.09.006
更新日期：2015-12-01 00:00:00
abstract：:The total number of the neuromelanin-containing neurons of the nucleus coeruleus was determined by means of a newly developed unbiased stereological counting scheme and a low-cost apparative set-up. The individuals (n = 20, age from 49-98 years) included in this study were carefully examined for absence of neurologica...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(97)00034-1
更新日期：1997-07-01 00:00:00
abstract：:Neuroimaging biomarkers differ between patients with early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD). Whether these changes reflect cognitive heterogeneity or differences in disease severity is still unknown. This study aimed at investigating changes in neuroimaging biomarkers, accordi...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2017.02.010
更新日期：2017-06-01 00:00:00
abstract：:Nonhuman primates (NHPs) are useful for the study of age-associated changes in the brain as a model that is biologically closely related to humans. For example, with age, all NHPs analyzed to date, develop β-amyloid (Aβ) plaques as seen in humans. Nevertheless, it is still unclear if NHPs have human-like age-associate...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.01.139
更新日期：2014-07-01 00:00:00
abstract：:Stroke is an important risk factor for dementia, but the exact mechanisms involved in cognitive decline remain unclear. In this study, we related baseline MRI brain measures with later cognitive decline. Seventy-nine stroke survivors aged 75+ years without dementia were recruited 3-month post-stroke. They underwent ye...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2006.07.009
更新日期：2007-11-01 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：:After a decade of intense study of cholinergic therapies for Alzheimer's disease, three conditions in this field are apparent: 1) The potential that cholinergic agents will ameliorate the memory dysfunction of Alzheimer patients (as 1-dopa benefits Parkinson patients) is still a stimulus for research. 2) Cholinergic n...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(89)80017-x
更新日期：1989-01-01 00:00:00
abstract：:The ability to maintain cognitive function during aging is a complex process subject to genetic and environmental influences. Alzheimer's disease (AD) is the most common disorder causing cognitive decline among the elderly. Among those with AD, there is broad variation in the relationship between AD neuropathology and...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2006.11.008
更新日期：2008-04-01 00:00:00
abstract：OBJECTIVE:To determine the patterns of cerebral glucose metabolism in frontotemporal dementia (FTD) and semantic dementia (SD). METHODS:25 patients with mild FTD and 9 patients with mild SD as well as 15 healthy age-matched control subjects underwent 18F-FDG- positron emission tomography. Patient scans were compared w...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2003.10.007
更新日期：2004-09-01 00:00:00
abstract：:While aged monkeys of several species show cerebral amyloid deposition in senile plaques and blood vessels similar to that seen in human aging and Alzheimer's disease (AD), studies of great apes have been limited. Using histological and immunohistochemical methods, we examined the brains of four orangutans aged 10, 28...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(97)00012-2
更新日期：1997-03-01 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：:Perhaps cognitive and brain imaging measures have been pushed almost as far as they can go in helping diagnose or understand AD. Their value may increase with the development of better models of the disease and the addition of new types of measurements to the armamentarium (e.g., eye-tracking, olfactory, and dermatogl...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(88)80033-2
更新日期：1988-01-01 00:00:00
abstract：:Mural cells (smooth muscle cells and pericytes) regulate blood flow and contribute to vessel stability. We examined whether mural cell changes accompany age-related alterations in the microvasculature of the central nervous system. The retinas of young adult and aged Wistar rats were subjected to immunohistofluorescen...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2005.10.021
更新日期：2006-12-01 00:00:00
abstract：:Posterior cingulate cortex (PCC) accumulates amyloid-β (Aβ) early in Alzheimer's disease (AD). The relative concentrations of full-length Aβ and truncated, pyroglutamate-modified Aβ (NpE3) forms, and their correlations to cognitive dysfunction in AD, are unknown. We quantified AβNpE3-42, AβNpE3-40, Aβ1-42, and Aβ1-40 ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.06.021
更新日期：2015-01-01 00:00:00
abstract：:Genetic analyses of patients with neurodegenerative disorders have identified multiple genes that need to be investigated for the presence of damaging variants. However, mutation analysis by Sanger sequencing is costly and time consuming. We tested the utility of a recently designed semi-custom genome-wide array (Neur...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.07.038
更新日期：2015-01-01 00:00:00
abstract：:We investigated the effect of apolipoprotein E (apoE) genotype on amyloid load in the frontal and cerebellar cortices of 24 patients with definite Alzheimer disease (AD) and 19 controls. Amyloid load was examined by using two methods: 1) acid-extractable amyloid beta-protein (A beta) and insoluble A beta levels of fro...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(96)00204-7
更新日期：1997-01-01 00:00:00
abstract：:Biochemical, genetic, and epidemiological evidence indicates that inflammation is an essential part of the pathogenesis of Alzheimer's disease. Over the last decade, we and others have focused on the mechanism by which specific inflammatory molecules contribute to the Alzheimer pathogenic pathway. In particular, we ha...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/s0197-4580(01)00308-6
更新日期：2001-11-01 00:00:00
abstract：:Frontotemporal lobar degeneration is a neuropathological disorder that causes a variety of clinical syndromes including frontotemporal dementia (FTD), progressive supranuclear palsy, and corticobasal syndrome (CBS). FTD associated with parkinsonism occurs frequently as a result of mutations in the C9orf72 gene and als...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2017.02.002
更新日期：2017-05-01 00:00:00
abstract：:DNA methylation is an important regulatory mechanism of Parkinson's disease (PD). To investigate the relationship between DNA methylation and hydroxymethylation genes and PD, we performed gene-targeted sequencing using molecular inversion probes in a Chinese PD population. We sequenced 12 genes related to DNA methylat...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2019.02.025
更新日期：2019-12-01 00:00:00
abstract：:The impact of many inflammatory diseases is influenced by age-related changes in the activation of resident and circulating myeloid cells. In the eye, a major sight-threatening consequence of age-related macular degeneration is the development of severe choroidal neovascularization (CNV). To identify the molecular pat...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2015.12.019
更新日期：2016-04-01 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：: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：:The loss of presynaptic markers is thought to represent a strong pathologic correlate of cognitive decline in Alzheimer's disease (AD). Spinophilin is a postsynaptic marker mainly located to the heads of dendritic spines. We assessed total numbers of spinophilin-immunoreactive puncta in the CA1 and CA3 fields of hippo...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2007.03.007
更新日期：2008-09-01 00:00:00
abstract：:The neuroprotective effects of menopausal hormonal therapy in Parkinson's disease have not yet been clarified, and it is not known whether there is a critical period. Estrogen induced significant protection against 6-hydroxydopamine-induced dopaminergic degeneration when administered immediately or 6 weeks, but not 20...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.10.028
更新日期：2015-02-01 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：:Here we employed human SHEP neuroblastoma cells either stably or inducibly expressing the amyloid precursor protein (APP) intracellular domain (AICD) to investigate its ability to modulate stress-induced cell death. Analysis of effector caspase activation revealed that AICD overexpression was specifically associated w...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.06.012
更新日期：2012-09-01 00:00:00
