Abstract:
:Neuroinflammation and autophagy dysfunction are closely related to the development of neurodegeneration such as Parkinson's disease (PD). However, the role of autophagy in microglia polarization and neuroinflammation is poorly understood. TNF-α, which is highly toxic to dopaminergic neurons, is implicated as a major mediator of neuroinflammation in PD. In this study, we found that TNF-α resulted in an impairment of autophagic flux in microglia. Concomitantly, an increase of M1 marker (iNOS/NO, IL-1β, and IL-6) expression and reduction of M2 marker (Arginase1, Ym1/2, and IL-10) were observed in TNF-α challenged microglia. Upregulation of autophagy via serum deprivation or pharmacologic activators (rapamycin and resveratrol) promoted microglia polarization toward M2 phenotype, as evidenced by suppressed M1 and elevated M2 gene expression, while inhibition of autophagy with 3-MA or Atg5 siRNA consistently aggravated the M1 polarization induced by TNF-α. Moreover, Atg5 knockdown alone was sufficient to trigger microglia activation toward M1 status. More important, TNF-α stimulated microglia conditioned medium caused neurotoxicity when added to neuronal cells. The neurotoxicity was further aggravated when Atg5 knockdown in BV2 cells but alleviated when microglia pretreatment with rapamycin. Activation of AKT/mTOR signaling may contribute to the changes of autophagy and inflammation as the AKT specific inhibitor perifosine prevented the increase of LC3II (an autophagic marker) in TNF-α stimulated microglia. Taking together, our results demonstrate that TNF-α inhibits autophagy in microglia through AKT/mTOR signaling pathway, and autophagy enhancement can promote microglia polarization toward M2 phenotype and inflammation resolution.
journal_name
Front Aging Neuroscijournal_title
Frontiers in aging neuroscienceauthors
Jin MM,Wang F,Qi D,Liu WW,Gu C,Mao CJ,Yang YP,Zhao Z,Hu LF,Liu CFdoi
10.3389/fnagi.2018.00378subject
Has Abstractpub_date
2018-11-20 00:00:00pages
378issn
1663-4365journal_volume
10pub_type
杂志文章abstract::Herpes simplex virus type 1 (HSV1), when present in brain of carriers of the type 4 allele of the apolipoprotein E gene (APOE), has been implicated as a major factor in Alzheimer's disease (AD). It is proposed that virus is normally latent in many elderly brains but reactivates periodically (as in the peripheral nervo...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnagi.2014.00202
更新日期:2014-08-11 00:00:00
abstract:Background and Purpose:To identify clinical, laboratory, and magnetic resonance imaging (MRI) features in predicting incident stroke and dementia in Korean patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Materials and Methods:We enrolled 87 Korean CAD...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2020.591879
更新日期:2020-11-20 00:00:00
abstract::[This corrects the article on p. 13 in vol. 8, PMID: 26903857.]. ...
journal_title:Frontiers in aging neuroscience
pub_type: 已发布勘误
doi:10.3389/fnagi.2017.00035
更新日期:2017-02-23 00:00:00
abstract::The cognitive reserve hypothesis claims that the brain can overcome pathology by reinforcing preexistent processes or by developing alternative cognitive strategies. Epidemiological studies have revealed that this reserve can be built throughout life experiences as education or leisure activities. We previously showed...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2015.00178
更新日期:2015-09-23 00:00:00
abstract::This study aimed to explore the effects of open- and closed-skill exercise interventions on the neurocognitive performance of executive functions in the elderly. Sixty-four healthy elderly males were randomly assigned to either a closed-skill (bike riding or brisk walking/jogging, n = 22), open-skill (table tennis, n ...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2017.00294
更新日期:2017-09-12 00:00:00
abstract::Mouse models are key tools for studying cochlear alterations in noise-induced hearing loss (NIHL) and for evaluating new therapies. Stimuli used to induce deafness in mice are usually white and octave band noises that include very low frequencies, considering the large mouse auditory range. We designed different sound...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2015.00007
更新日期:2015-02-16 00:00:00
abstract::Background and Purpose: Olfactory dysfunction (OD) is a common non-motor symptom of Parkinson disease (PD). However, the relationship between OD and neuropathologic proteins in cerebrospinal fluid (CSF) from PD patients remains unclear. Methods: 166 PD patients were included in the study. Overall olfactory function wa...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2020.594324
更新日期:2020-12-11 00:00:00
abstract::Introduction: Cognitive screening in settings such as emergency departments (ED) is frequently carried out using paper-and-pencil tests that require administration by trained staff. These assessments often compete with other clinical duties and thus may not be routinely administered in these busy settings. Literature ...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2016.00258
更新日期:2016-11-07 00:00:00
abstract::Background: Primary progressive aphasia (PPA) is a clinical syndrome characterized by the neurodegeneration of language brain systems. Three main clinical forms (non-fluent, semantic, and logopenic PPA) have been recognized, but applicability of the classification and the capacity to predict the underlying pathology i...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2018.00230
更新日期:2018-07-31 00:00:00
abstract::Alzheimer's disease (AD) is a multifactorial neurodegenerative disease. It begins years prior to the onset of clinical symptoms, such as memory loss and cognitive decline. Pathological hallmarks of AD include the accumulation of β-amyloid in plaques and hyperphosphorylated tau in neurofibrillary tangles. Copper, iron,...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnagi.2014.00091
更新日期:2014-05-15 00:00:00
abstract::Electroacupuncture (EA) has been reported to have beneficial effects on Alzheimer's disease (AD). BACE1 (β-site amyloid precursor protein-cleaving enzyme 1) is involved in the abnormal production of amyloid-β plaque (Aβ), a hallmark of AD pathophysiology. Thus, the present study investigated the effects of EA on memor...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2015.00148
更新日期:2015-07-29 00:00:00
abstract::Activity-dependent neuroprotective protein (ADNP) is deregulated in Alzheimer's disease (AD) and in schizophrenia and mutated in autism. In mice, ADNP is essential for brain formation and ADNP haploinsufficiency is associated with cognitive and social deficits and tauopathy. Tauopathy, a major pathology in AD, is also...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnagi.2015.00205
更新日期:2015-10-29 00:00:00
abstract::We examined whether baseline self-reported physical activity is associated with the efficacy of cognitive behavioral therapy for insomnia (CBT-I) in older veterans. Community-dwelling veterans aged 60 years and older with insomnia received CBT-I in a randomized controlled trial. Participants who received active treatm...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2018.00274
更新日期:2018-09-13 00:00:00
abstract::The obesity epidemic had spawned considerable interest in understanding peoples' responses to palatable food cues that are plentiful in obesogenic environments. In this paper we examine how trait mindfulness of older, obese adults may moderate brain networks that arise from exposure to such cues. Nineteen older, obese...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2012.00013
更新日期:2012-06-06 00:00:00
abstract::Objectives: Postural control in elderly people is impaired by degradations of sensory, motor, and higher-level adaptive mechanisms. Here, we characterize the effects of a progressive balance training program on these postural control impairments using a brain network model based on system identification techniques. Me...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2017.00273
更新日期:2017-08-11 00:00:00
abstract::Postoperative cognitive dysfunction (POCD) is a significant complication of surgery, particularly in elderly patients. Emerging researches showed that long non-coding RNA (lncRNA) may play a vital role in the pathogenesis of POCD. Here we aimed to identify potential key lncRNAs involved in the development of POCD. Lnc...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2019.00181
更新日期:2019-07-17 00:00:00
abstract::A defining pathophysiological hallmark of Alzheimer's disease (AD) is the amyloid plaque; an extracellular deposit of aggregated fibrillar Aβ1-42 peptides. Amyloid plaques are hard, brittle structures scattered throughout the hippocampus and cerebral cortex and are thought to cause hyperphosphorylation of tau, neurofi...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2018.00332
更新日期:2018-10-22 00:00:00
abstract::Understanding speech in the presence of background sound can be challenging for older adults. Speech comprehension in noise appears to depend on working memory and executive-control processes (e.g., Heald and Nusbaum, 2014), and their augmentation through training may have rehabilitative potential for age-related hear...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2016.00049
更新日期:2016-03-22 00:00:00
abstract::Frontotemporal lobar degeneration (FTLD) is a severe neurodegenerative disorder that is diagnosed with increasing frequency in clinical setting. Currently, no therapy is available and in addition the molecular basis of the disease are far from being elucidated. Consequently, it is of pivotal importance to develop reli...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2016.00146
更新日期:2016-06-22 00:00:00
abstract::The aim of this study was to develop a fast method for estimating whether a brain volume loss is within the normal range for the respective age of the patient. A readout-segmented diffusion-weighted echo-planar imaging sequence was performed as part of the routine examination at a 3-T scanner. Data without (b0-image) ...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2013.00078
更新日期:2013-11-19 00:00:00
abstract:OBJECTIVE:Early-onset Alzheimer's disease (EAD) shows distinct features from late-onset Alzheimer's disease (LAD). To explore the characteristics of EAD, clinical, neuropsychological, and functional imaging studies have been conducted. However, differences between EAD and LAD are not clear, especially in terms of brain...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2016.00159
更新日期:2016-06-30 00:00:00
abstract:Background:Despite known associations of lower serum uric acid (UA) with Alzheimer's disease (AD) dementia or AD-related cognitive impairment, little is known regarding the underlying patho-mechanisms. We aimed to examine the relationships of serum UA with in vivo AD pathologies including cerebral beta-amyloid (Aβ) and...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2020.00160
更新日期:2020-06-05 00:00:00
abstract::This study investigated age-related changes in the neural bases of sequential strategy interference. Sequential strategy interference refers to decreased strategy interference (i.e., poorer performance when the cued strategy is not the best) after executing a poorer strategy relative to after a better strategy. Young ...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2018.00232
更新日期:2018-08-08 00:00:00
abstract::Neuroimaging-based age prediction using machine learning is proposed as a biomarker of brain aging, relating to cognitive performance, health outcomes and progression of neurodegenerative disease. However, even leading age-prediction algorithms contain measurement error, motivating efforts to improve experimental pipe...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2018.00028
更新日期:2018-02-12 00:00:00
abstract::Previous studies investigating working memory performance in patients with mild cognitive impairment (MCI) have mainly focused on the neural mechanisms of alterations in activation. To date, very few studies have investigated background network alterations in the working memory state. Therefore, the present study inve...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2019.00152
更新日期:2019-06-28 00:00:00
abstract::Amyloid-beta (Aβ) in Alzheimer's disease (AD) appeared to be a promising target for disease-modifying therapeutic strategies like passive immunotherapy with anti-Aβ monoclonal antibodies (mAbs). Biochemical markers in cerebrospinal fluid (CSF) include alterations of Aβ that allow the diagnosis of AD. Biomarker strateg...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2013.00025
更新日期:2013-07-02 00:00:00
abstract::Recent work suggests that the brain can be conceptualized as a network comprised of groups of sub-networks or modules. The extent of segregation between modules can be quantified with a modularity metric, where networks with high modularity have dense connections within modules and sparser connections between modules....
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2017.00426
更新日期:2018-01-04 00:00:00
abstract::Alzheimer's disease (AD) is the most common form of dementia diagnosed amongst the elderly. Mild cognitive impairment (MCI) is a condition often indicative of the earliest symptomatology of AD with 10%-15% of MCI patients reportedly progressing to a diagnosis of AD. Individuals with a history of vascular risk factors ...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnagi.2017.00048
更新日期:2017-03-03 00:00:00
abstract::Aging is associated with cognitive decline and alterations in early perceptual processes. Studies in the auditory and visual sensory modalities have shown that the mismatch negativity [or the mismatch response (MMR)], an event-related potential (ERP) elicited by a deviant stimulus in a background of homogenous events,...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2014.00293
更新日期:2014-10-27 00:00:00
abstract:BACKGROUND:During the last two decades, protein aggregation at all organismal levels, from viruses to humans, has emerged from a neglected area of protein science to become a central issue in biology and biomedicine. This article constitutes a risk-based review aimed at supporting an etiologic scenario of selected, spo...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2016.00138
更新日期:2016-06-13 00:00:00