Abstract:
:Microglial activation is a key pathogenic process at the onset of Alzheimer's disease (AD). Identifying regulators of microglial activation bears great potential in elucidating causes and mechanisms of AD and determining candidates for early intervention. Previous studies demonstrate abnormal elevation of glutaminase C (GAC) in HIV-infected or immune-activated microglia. However, whether GAC elevation causes microglial activation remains unknown. In this study, we found heightened expression levels of GAC in early AD mouse brain tissues compared with those in control littermates. Investigations on an in vitro neuroinflammation model revealed that GAC is increased in primary mouse microglia following pro-inflammatory stimulation. To model GAC elevation we overexpressed GAC by plasmid transfection and observed that GAC-overexpression shift the microglial phenotype to a pro-inflammatory state. Treatment with BPTES, a glutaminase inhibitor, reversed LPS-induced microglial activation and inflammation. Furthermore, we discovered that GAC overexpression in mouse microglia increased exosome release and changed exosome content, which includes specific packaging of pro-inflammatory miRNAs that activate microglia. Together, our results demonstrate a causal effect of GAC elevation on microglial activation and exosome release, both of which promote the establishment of a pro-inflammatory microenvironment. Therefore, GAC may have important relevance to the pathogenesis of AD.
journal_name
Front Cell Neuroscijournal_title
Frontiers in cellular neuroscienceauthors
Gao G,Zhao S,Xia X,Li C,Li C,Ji C,Sheng S,Tang Y,Zhu J,Wang Y,Huang Y,Zheng JCdoi
10.3389/fncel.2019.00264subject
Has Abstractpub_date
2019-06-28 00:00:00pages
264issn
1662-5102journal_volume
13pub_type
杂志文章abstract::Cerebral ischemic stroke is regarded as one of the most serious diseases in the human central nervous system. The secondary ischemia and reperfusion (I/R) injury increased the difficulty of treatment. Moreover, the latent molecular regulating mechanism in I/R injury is still unclear. Based on our previous clinical stu...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2020.00193
更新日期:2020-07-15 00:00:00
abstract::The phase of firing of hippocampal neurons during theta oscillations encodes spatial information. Moreover, the spike phase response to synaptic inputs in individual cells depends on the expression of the hyperpolarization-activated mixed cation current (I h ), which differs between CA3 and CA1 pyramidal neurons. Here...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2013.00263
更新日期:2013-12-25 00:00:00
abstract::To find satisfactory treatment strategies for neuropathic pain syndromes, the cellular mechanisms should be illuminated. Central sensitization is a generator of pain hypersensitivity, and is mainly reflected in neuronal hyperexcitability in pain pathway. Neuronal excitability depends on two components, the synaptic in...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2018.00436
更新日期:2018-11-21 00:00:00
abstract::Fragile X Syndrome (FXS) is caused by a deficiency in Fragile X Mental Retardation Protein (FMRP) leading to global sensorial abnormalities, among which visual defects represent a critical part. These visual defects are associated with cerebral neuron immaturity especially in the primary visual cortex. However, we rec...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2018.00096
更新日期:2018-04-06 00:00:00
abstract::Adeno-associated virus (AAV) is the preferred vector for gene therapy of hereditary deafness, and different viral serotypes, promoters and transduction pathways can influence the targeting of AAV to different types of cells and the expression levels of numerous exogenous genes. To determine the transduction and expres...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2019.00008
更新日期:2019-01-24 00:00:00
abstract::Gastrointestinal (GI) pain is a common clinical problem, for which effective therapy is quite limited. Sensations from the GI tract, including pain, are mediated largely by neurons in the dorsal root ganglia (DRG), and to a smaller extent by vagal afferents emerging from neurons in the nodose/jugular ganglia. Neurons ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2015.00412
更新日期:2015-10-13 00:00:00
abstract::The present study was designed to observe the effect of COX2/PGD2-related autophagy on brain injury in type 2 diabetes rats. The histopathology was detected by haematoxylin-eosin staining. The learning and memory functions were evaluated by Morris water maze. The levels of insulin and PGD2 were measured by enzyme-link...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2019.00068
更新日期:2019-02-27 00:00:00
abstract::Chronic inflammation and oxidative stress (OS) are present in Alzheimer's disease (AD) brains in addition to neuronal loss, Amyloid-β (Aβ) plaques and hyperphosphorylated tau-protein neurofibrillary tangles (NFTs). Previously we showed that levels of the pro-inflammatory cytokine, interleukin-18 (IL-18), are elevated ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2014.00214
更新日期:2014-08-07 00:00:00
abstract::Proper transport of the Parkinson's disease (PD) protein, α-synuclein (α-syn), is thought to be crucial for its localization and function at the synapse. Previous work has shown that defects in long distance transport within narrow caliber axons occur early in PD, but how such defects contribute to PD is unknown. Here...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2019.00540
更新日期:2020-01-10 00:00:00
abstract::Oligodendrocytes are the myelinating cells of the central nervous system (CNS). While the phrase is oft repeated and holds true, the last few years have borne witness to radical change in our understanding of this unique cell type. Once considered static glue, oligodendrocytes are now seen as plastic and adaptive, cap...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2015.00340
更新日期:2015-09-01 00:00:00
abstract::Members of the Shank family of multidomain proteins (Shank1, Shank2, and Shank3) are core components of the postsynaptic density (PSD) of excitatory synapses. At synaptic sites Shanks serve as scaffolding molecules that cluster neurotransmitter receptors as well as cell adhesion molecules attaching them to the actin c...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2016.00106
更新日期:2016-04-26 00:00:00
abstract::The GABAB receptor agonist, baclofen, is used to treat muscle tightness and cramping caused by spasticity in a number of disorders including multiple sclerosis (MS), but its precise mechanism of action is unknown. Neuroinflammation drives the central pathology in MS and is mediated by both immunoreactive glial cells a...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2015.00284
更新日期:2015-07-28 00:00:00
abstract::In vitro approaches have suggested that neuropsin (or kallikrein 8/KLK8), which controls gamma-aminobutyric acid (GABA) neurotransmission through neuregulin-1 (NRG-1) and its receptor (ErbB4), is involved in neural plasticity (Tamura et al., 2012, 2013). In the present study, we examined whether parvalbumin (PV)-posit...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2014.00420
更新日期:2014-12-10 00:00:00
abstract::[This corrects the article DOI: 10.3389/fncel.2019.00150.]. ...
journal_title:Frontiers in cellular neuroscience
pub_type: 已发布勘误
doi:10.3389/fncel.2019.00388
更新日期:2019-08-22 00:00:00
abstract::While task-dependent responses of specific brain areas during cognitive tasks are well established, much less is known about the changes occurring in resting state networks (RSNs) in relation to continuous cognitive processing. In particular, the functional involvement of cerebro-cerebellar loops connecting the poster...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2018.00331
更新日期:2018-10-01 00:00:00
abstract::Gene knockout by homologous recombination is a popular method to study gene functions in the mouse in vivo. However, its lack of temporal control has limited the interpretation of knockout studies because the complete elimination of a gene product often alters developmental processes, and can induce severe malformatio...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2014.00062
更新日期:2014-03-19 00:00:00
abstract::The cerebral cortical tissue of murine embryo and pluripotent stem cell (PSC)-derived neurons can survive in the brain and extend axons to the spinal cord. For efficient cell integration to the corticospinal tract (CST) after transplantation, the induction or selection of cortical motor neurons is important. However, ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2017.00123
更新日期:2017-05-01 00:00:00
abstract::Functional maturation of visual cortex is linked with dynamic changes in synaptic expression of GABAergic mechanisms. These include setting the excitation-inhibition balance required for experience-dependent plasticity, as well as, intracortical inhibition underlying development and aging of receptive field properties...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2010.00016
更新日期:2010-06-10 00:00:00
abstract::The axon provides a sole output of the neuron which propagates action potentials reliably to the axon terminal and transmits neuronal information to the postsynaptic neuron across the synapse. A classical view of neuronal signaling is based on these two processes, namely binary (all or none) signaling along the axon a...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2019.00407
更新日期:2019-09-06 00:00:00
abstract::Orexin and melanin-concentrating hormone (MCH) neurons have complementary roles in various physiological functions including energy balance and the sleep/wake cycle. in vitro electrophysiological studies investigating these cells typically use post-weaning rodents, corresponding to adolescence. However, it is unclear ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2018.00070
更新日期:2018-03-13 00:00:00
abstract::Neurodegenerative diseases in general and specifically late-onset Alzheimer's disease (LOAD) involve a genetically complex and largely obscure ensemble of causative and risk factors accompanied by complex feedback responses. The advent of "high-throughput" transcriptome investigation technologies such as microarray an...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2014.00089
更新日期:2014-03-27 00:00:00
abstract::Behavioral and electrophysiological studies of Alzheimer's disease (AD) and other tauopathies have revealed that the onset of cognitive decline correlates better with synaptic dysfunctions than with hallmark pathologies such as extracellular amyloid-β plaques, intracellular hyperphosphorylated tau or neuronal loss. Re...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2014.00034
更新日期:2014-02-10 00:00:00
abstract::Inflammatory cells may contribute to secondary brain injury following cerebral ischemia. The C57Bl/6 mouse strain is known to exhibit a T helper 1-prone, pro-inflammatory type response to injury, whereas the FVB strain is relatively T helper 2-prone, or anti-inflammatory, in its immune response. We tested whether stro...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2014.00365
更新日期:2014-11-19 00:00:00
abstract::Tyrosine hydroxylase (Th) expression has previously been reported in Purkinje cells (PCs) of rodents and humans, but its role in the regulation of behavior is not understood. Catecholamines are well known for facilitating cognitive behaviors and are expressed in many regions of the brain. Here, we investigated a possi...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2020.00228
更新日期:2020-07-29 00:00:00
abstract::Gonadotropin releasing hormone-1 (GnRH-1) neurons play a pivotal role in controlling pubertal onset and fertility once they reach their hypothalamic location. During embryonic development, GnRH-1 neurons migrate from the nasal area to the hypothalamus where they modulate gonadotropin release from the pituitary gland. ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2019.00070
更新日期:2019-03-01 00:00:00
abstract::There is growing recognition that fast mitochondrial transport in neurons is disrupted in multiple neurological diseases and psychiatric disorders. However, a major constraint in identifying novel therapeutics based on mitochondrial transport is that the large-scale analysis of fast transport is time consuming. Here w...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2015.00435
更新日期:2015-11-03 00:00:00
abstract::GABA transporters belong to a large family of neurotransmitter:sodium symporters. They are widely expressed throughout the brain, with different levels of expression in different brain regions. GABA transporters are present in neurons and in astrocytes and their activity is crucial to regulate the extracellular concen...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2014.00161
更新日期:2014-06-17 00:00:00
abstract::In this review, we discuss molecular and cellular mechanisms important for the function of neuronal progenitors during development, revealed by their perturbation in different cortical malformations. We focus on a class of neuronal progenitors, radial glial cells (RGCs), which are renowned for their unique morphologic...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2015.00030
更新日期:2015-02-12 00:00:00
abstract::The malignancy of glioblastoma multiform (GBM), the most common and aggressive form of human brain tumors, strongly correlates with the presence of hypoxic areas, but the mechanisms controlling the hypoxia-induced aggressiveness are still unclear. GBM cells express a number of ion channels whose activity supports cell...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2014.00467
更新日期:2015-01-15 00:00:00
abstract::The brain is a plastic organ where both the intrinsic CNS milieu and extrinsic cues play important roles in shaping and wiring neural connections. The perinatal period constitutes a critical time in central nervous system development with extensive refinement of neural connections, which are highly sensitive to fetal ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2017.00190
更新日期:2017-07-11 00:00:00