Abstract:
:Constitutive expression of C-C chemokine receptor (CCR) 5 has been detected in astrocytes, microglia and neurons, but its physiological roles in the central nervous system are obscure. The bidirectional interactions between neuron and glial cells through CCR5 and its ligands were thought to be crucial for maintaining normal neuronal activities. No study has described function of CCR5 in the dopaminergic neurodegeneration in Parkinson's disease. In order to examine effects of CCR5 on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration, we employed CCR5 wild type (WT) and knockout (KO) mice. Immunostainings for tyrosine hydroxylase (TH) exhibited that CCR5 KO mice had lower number of TH-positive neurons even in the absence of MPTP. Difference in MPTP (15mg/kg×4 times, 2hr interval)-mediated loss of TH-positive neurons was subtle between CCR5 WT and KO mice, but there was larger dopamine depletion, behavioral impairments and microglial activation in CCR5 deficient mice. Intriguingly, CCR5 KO brains contained higher immunoreactivity for monoamine oxidase (MAO) B which was mainly localized within astrocytes. In agreement with upregulation of MAO B, concentration of MPP+ was higher in the substantia nigra and striatum of CCR5 KO mice after MPTP injection. We found remarkable activation of p38 MAPK in CCR5 deficient mice, which positively regulates MAO B expression. These results indicate that CCR5 deficiency modifies the nigrostriatal dopaminergic neuronal system and bidirectional interaction between neurons and glial cells via CCR5 might be important for dopaminergic neuronal survival.
journal_name
Neurobiol Disjournal_title
Neurobiology of diseaseauthors
Choi DY,Lee MK,Hong JTdoi
10.1016/j.nbd.2012.08.001subject
Has Abstractpub_date
2013-01-01 00:00:00pages
159-68eissn
0969-9961issn
1095-953Xpii
S0969-9961(12)00288-4journal_volume
49pub_type
杂志文章abstract::Shed photoreceptor outer segments (POS) are phagocytosed by RPE cells in a circadian manner. The homozygous deletion of the c-mer gene abolishes the ingestion phase of this phagocytosis in the Royal College of Surgeons (RCS) rat strain, which in turn leads to the death of photoreceptor cells. We identified RPE transcr...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/s0969-9961(03)00102-5
更新日期:2003-11-01 00:00:00
abstract::Charcot-Marie-Tooth disease type 2B (CMT2B) is an inherited axonal peripheral neuropathy. It is characterised by prominent sensory loss, often complicated by severe ulcero-mutilations of toes or feet, and variable motor involvement. Missense mutations in RAB7A, the gene encoding the small GTPase Rab7, cause CMT2B and ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2014.01.021
更新日期:2014-05-01 00:00:00
abstract::Voltage-gated sodium channels (VGSCs) are essential for the generation and propagation of action potentials in electrically excitable cells. Dominant mutations in SCN1A, which encodes the Nav1.1 VGSC α-subunit, underlie several forms of epilepsy, including Dravet syndrome (DS) and genetic epilepsy with febrile seizure...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2012.08.012
更新日期:2013-01-01 00:00:00
abstract::Exposure to stress during pregnancy influences the trajectory of brain development resulting in permanent alterations that may contribute to increased susceptibility to subsequent cognitive or neuropsychiatric disorders. In this manuscript, we examined the effects of prenatal stress on the expression of basic fibrobla...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.05.005
更新日期:2005-12-01 00:00:00
abstract::Familial amyotrophic lateral sclerosis (FALS) has been modeled in transgenic mice by introducing mutated versions of human genomic DNA encompassing the entire gene for Cu,Zn superoxide dismutase (SOD1). In this setting, the transgene is expressed throughout the body and results in mice that faithfully recapitulate man...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.06.005
更新日期:2005-12-01 00:00:00
abstract::Ample evidence has surfaced documenting the neurotoxic effects of various general anesthetic (GA) agents in the mammalian brain when administered at critical periods of synaptogenesis. However, little is known about how this neurotoxic insult affects persisting neuronal excitability after the initial exposure. Here we...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2019.01.016
更新日期:2019-07-01 00:00:00
abstract::Excitotoxicity plays a central role in the neuronal damage during ischemic stroke. Although growing evidence suggests that activation of extrasynaptic NMDA receptors initiates neuronal death, no direct evidence demonstrated their activation during ischemia. Using rat hippocampal slices, we detected oxygen-glucose depr...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2013.05.005
更新日期:2013-10-01 00:00:00
abstract::The mutilated-foot rat (mf rat) is an autosomal recessive mutant with characteristic digit deformities in adult animals, and this phenotype mimics many aspects of human sensory neuropathy. The genetics of mf rats was recently elucidated. To understand whether the genotype is responsible for cutaneous denervation befor...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2004.03.003
更新日期:2004-07-01 00:00:00
abstract::In the present study we analyze the molecular mechanisms underlying motor neuron degeneration in familial amyotrophic lateral sclerosis (FALS). For this, we used a transgenic mouse model expressing the Cu/Zn superoxide dismutase (SOD1) gene with a Gly(86) to Arg (G86R) mutation equivalent to that found in a subset of ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1006/nbdi.2000.0292
更新日期:2000-08-01 00:00:00
abstract::The human motor system has the capacity to act as an internal form of analgesia. Since the discovery of the potential influence of motor systems on analgesia in rodent models, clinical applications of targeting the motor system for analgesia have been implemented. However, a neurobiological basis for motor activation'...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2020.105158
更新日期:2021-01-01 00:00:00
abstract::Amyloid beta-peptide (Abeta) containing plaques and neurofibrillary tangles (NFT) are the two major histopathological hallmarks of Alzheimer's disease (AD). According to the amyloid cascade hypothesis, deposition of Abeta is an initial and essential step in the pathogenesis of AD, and formation of NFT has been propose...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.10.002
更新日期:2006-04-01 00:00:00
abstract::Frontotemporal dementia (FTD) is the second most common type of primary degenerative dementia. Some patients present an overlap between Alzheimer's disease (AD) and FTD both in neuropathological and clinical aspects. This may suggest a similar overlap in physiopathology, namely an involvement of mitochondrial DNA (mtD...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2003.11.004
更新日期:2004-03-01 00:00:00
abstract::Patients with Krabbe disease, a genetic demyelinating syndrome caused by deficiency of galactosyl-ceramidase and the resulting accumulation of galactosyl-sphingolipids, develop signs of a dying-back axonopathy compounded by a deficiency of large-caliber axons. Here, we show that axonal caliber in Twitcher mice, an ani...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2012.01.013
更新日期:2012-05-01 00:00:00
abstract::Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized behaviorally by chorea, incoordination, and shortened lifespan and neuropathologically by huntingtin inclusions and neuronal degeneration. In order to facilitate studies of pathogenesis and therapeutics, we have generated a new...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.07.014
更新日期:2006-02-01 00:00:00
abstract::Extracellular matrix molecule chondroitin sulfate proteoglycans (CSPGs) are highly upregulated in scar tissues and form a potent chemical barrier for CNS axon regeneration. Recent studies support that the receptor protein tyrosine phosphatase σ (PTPσ) and its subfamily member leukocyte common antigen related phosphata...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2014.08.030
更新日期:2015-01-01 00:00:00
abstract::Low brain expression of the spermidine/spermine N-1 acetyltransferase (SAT1) gene, the rate-limiting enzyme involved in catabolism of polyamines that mediate the polyamine stress response (PSR), has been reported in depressed suicides. However, it is unknown whether this effect is associated with depression or with su...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2015.04.014
更新日期:2015-07-01 00:00:00
abstract::The spreading of pathology through neuronal pathways is likely to be the cause of the progressive cognitive loss observed in Alzheimer's disease (AD) and other neurodegenerative diseases. We have recently shown the propagation of AD pathology via cell-to-cell transfer of oligomeric amyloid beta (Aβ) residues 1-42 (oAβ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2013.12.019
更新日期:2014-05-01 00:00:00
abstract::Recently, we showed that oxidative stress activates the expression and activity of the beta-site AbetaPP-cleaving enzyme (BACE), an aspartyl protease responsible for the beta-secretase cleavage of AbetaPP. The identification of compounds able to prevent the induction of this event is an important goal of therapeutic s...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/s0969-9961(03)00131-1
更新日期:2003-11-01 00:00:00
abstract::Cholesterol precursors and cholesterol levels are reduced in brain regions of Huntington's disease (HD) mice. Here we quantified the rate of in vivo de novo cholesterol biosynthesis in the HD brain. Samples from different brain regions and blood of the heterozygous knock-in mouse model carrying 175 CAG repeats (Q175) ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2016.11.013
更新日期:2017-02-01 00:00:00
abstract::During the last few years, adenoviral gene transfer techniques have achieved increasing interest in the treatment of neurodegenerative diseases. However, gene therapy requires that delivered genes are translated into proteins. This may pose a problem in focal ischemia where protein synthesis is compromized. The presen...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1006/nbdi.2001.0399
更新日期:2001-08-01 00:00:00
abstract::The disruption of the blood-spinal cord barrier (BSCB) by matrix metalloprotease (MMP) activation is a detrimental event that leads to blood cell infiltration, inflammation, and apoptosis, thereby contributing to permanent neurological disability after spinal cord injury (SCI). However, the molecular mechanisms underl...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2016.07.015
更新日期:2016-11-01 00:00:00
abstract::Alpha-synuclein (aSyn) is the major protein component of Lewy bodies and Lewy neurites, the typical pathological hallmarks in Parkinson's disease (PD) and Dementia with Lewy bodies. aSyn is capable of inducing transcriptional deregulation, but the precise effect of specific aSyn mutants associated with familial forms ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2018.08.001
更新日期:2018-11-01 00:00:00
abstract::Frontotemporal dementia (FTD) is one of the most prevalent forms of early-onset dementia. It represents part of the FTD-Amyotrophic Lateral Sclerosis (ALS) spectrum, a continuum of genetically and pathologically overlapping disorders. FTD-causing mutations in CHMP2B, a gene encoding a core component of the heteromeric...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2020.105047
更新日期:2020-10-01 00:00:00
abstract::Fragile X Syndrome (FXS) is a heritable form of mental retardation caused by a non-coding trinucleotide expansion of the FMR1 gene leading to loss of expression of this RNA binding protein. Mutations in this gene are strongly linked to enhanced Group I metabotropic glutamate receptor (mGluR) signaling. A recent report...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2013.04.002
更新日期:2013-08-01 00:00:00
abstract::This paper presents a novel model of tremor in Parkinson's disease (PD) based on extensive literature review as well as novel results stemming from functional stereotactic neurosurgery for the alleviation of tremor in PD. Specifically, evidence that suggests the basal ganglia induces PD tremor via excessive inhibitory...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2015.10.009
更新日期:2016-01-01 00:00:00
abstract::Background While significant advances have been made in uncovering the aetiology of Alzheimer's disease and related dementias at the genetic level, molecular events at the epigenetic level remain largely undefined. Emerging evidence indicates that small non-coding RNAs (sncRNAs) and their associated RNA modifications ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2020.105058
更新日期:2020-11-01 00:00:00
abstract::Infection of immunocompetent adult rats with Borna disease virus (BDV) causes severe encephalitis and neural dysfunction. The expression of COX-2 and CGRP, genes previously shown to be implicated in CNS disease and peripheral inflammation, was dramatically upregulated in the cortical neurons of acutely BDV-infected ra...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1006/nbdi.1998.0225
更新日期:1999-02-01 00:00:00
abstract::Although peroxisome biogenesis and β-oxidation disorders are well known for their neurodevelopmental defects, patients with these disorders are increasingly diagnosed with neurodegenerative pathologies. In order to investigate the cellular mechanisms of neurodegeneration in these patients, we developed a mouse model l...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2013.06.006
更新日期:2013-10-01 00:00:00
abstract::Over 1250 mutations in SCN1A, the Nav1.1 voltage-gated sodium channel gene, are associated with seizure disorders including GEFS+. To evaluate how a specific mutation, independent of genetic background, causes seizure activity we generated two pairs of isogenic human iPSC lines by CRISPR/Cas9 gene editing. One pair is...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2019.104627
更新日期:2020-02-01 00:00:00
abstract::We used quantal dose-titration of a mouse-adapted human transmissible spongiform encephalopathy strain (M470) to compare different analytical methods for their ability to detect asymptomatic brain prion infection after low dose inoculation. At a time point approximately 2.5-fold beyond the mean incubation period of hi...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.03.014
更新日期:2005-11-01 00:00:00