Differences in the distribution, phenotype and gene expression of subretinal microglia/macrophages in C57BL/6N (Crb1 rd8/rd8) versus C57BL6/J (Crb1 wt/wt) mice.


BACKGROUND:Microglia/macrophages (MG/MΦ) are found in the subretinal space in both mice and humans. Our goal was to study the spatial and temporal distribution, the phenotype, and gene expression of subretinal MG/MΦ in mice with normal retinas and compare them to mice with known retinal pathology. METHODS:We studied C57BL/6 mice with (C57BL/6N), or without (C57BL/6J) the rd8 mutation in the Crb1 gene (which, in the presence of yet unidentified permissive/modifying genes, leads to a retinal degeneration), and documented their fundus appearance and the change with aging. Immunostaining of retinal pigment epithelium (RPE) flat mounts was done for 1) Ionized calcium binding adaptor (Iba)-1, 2) FcγIII/II Receptor (CD16/CD32, abbreviated as CD16), and 3) Macrophage mannose receptor (MMR). Reverse-transcription quantitative PCR (RT-qPCR) was done for genes involved in oxidative stress, complement activation and inflammation. RESULTS:The number of yellow fundus spots correlated highly with subretinal Iba-1+ cells. The total number of subretinal MG/MΦ increased with age in the rd8 mutant mice, but not in the wild-type (WT) mice. There was a centripetal shift in the distribution of the subretinal MG/MΦ with age. Old rd8 mutant mice had a greater number of CD16+ MG/MΦ. CD16+ cells had morphological signs of activation, and this was most prominent in old rd8 mutant mice (P < 1 × 10(-8) versus old WT mice). Subretinal MG/MΦ in rd8 mutant mice also expressed iNOS and MHC-II, and had ultrastructural signs of activation. Finally, rd8 mutant mouse RPE/ MG/MΦ RNA isolates showed an upregulation of Ccl2, CFB, C3, NF-kβ, CD200R and TNF-alpha. The retinas of rd8 mutant mice showed upregulation of HO-1, C1q, C4, and Nrf-2. CONCLUSIONS:When compared to C57BL/6J mice, C57BL/6N mice demonstrate increased accumulation of subretinal MG/MΦ, displaying phenotypical, morphological, and gene-expression characteristics consistent with a pro-inflammatory shift. These changes become more prominent with aging and are likely due to the combination of the rd8 mutation and yet unidentified permissive/modulatory genes in the C57BL/6N mice. In contrast, aging leads to a scavenging phenotype in the C57BL/6J subretinal microglia/macrophages.


J Neuroinflammation


Aredo B,Zhang K,Chen X,Wang CX,Li T,Ufret-Vincenty RL




Has Abstract


2015-01-15 00:00:00










  • Intra-amniotic LPS causes acute neuroinflammation in preterm rhesus macaques.

    abstract:BACKGROUND:Chorioamnionitis is associated with an increased risk of brain injury in preterm neonates. Inflammatory changes in brain could underlie this injury. Here, we evaluated whether neuroinflammation is induced by chorioamnionitis in a clinically relevant model. METHODS:Rhesus macaque fetuses were exposed to eith...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Schmidt AF,Kannan PS,Chougnet CA,Danzer SC,Miller LA,Jobe AH,Kallapur SG

    更新日期:2016-09-06 00:00:00

  • CCL20-CCR6 axis modulated traumatic brain injury-induced visual pathologies.

    abstract:BACKGROUND:Traumatic brain injury (TBI) is a major cause of death and disability in the USA and the world; it constitutes 30% of injury-related deaths (Taylor et al., MMWR Surveill Summ 66:1-16, 2017). Contact sports athletes often experience repetitive TBI (rTBI), which exerts a cumulative effect later in life. Visual...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Das M,Tang X,Han JY,Mayilsamy K,Foran E,Biswal MR,Tzekov R,Mohapatra SS,Mohapatra S

    更新日期:2019-05-31 00:00:00

  • More than just inflammation: Ureaplasma species induce apoptosis in human brain microvascular endothelial cells.

    abstract:BACKGROUND:Ureaplasma species (spp.) are commonly regarded as low-virulent commensals but may cause invasive diseases in immunocompromised adults and in neonates, including neonatal meningitis. The interactions of Ureaplasma spp. with host defense mechanisms are poorly understood. This study addressed Ureaplasma-driven...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Silwedel C,Haarmann A,Fehrholz M,Claus H,Speer CP,Glaser K

    更新日期:2019-02-14 00:00:00

  • Early life overfeeding impairs spatial memory performance by reducing microglial sensitivity to learning.

    abstract:BACKGROUND:Obesity can lead to cognitive dysfunction including poor performance in memory tasks. However, poor memory is not seen in all obese humans and takes several months to develop in animal models, indicating the adult brain is relatively resistant to obesity's cognitive effects. We have seen that, in the rat, ov...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: De Luca SN,Ziko I,Sominsky L,Nguyen JC,Dinan T,Miller AA,Jenkins TA,Spencer SJ

    更新日期:2016-05-18 00:00:00

  • Neural networks and the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation in depression.

    abstract::Transcutaneous auricular vagus nerve stimulation (taVNS) is a relatively non-invasive alternative treatment for patients suffering from major depressive disorder (MDD). It has been postulated that acupuncture may achieve its treatment effects on MDD through suppression of vagal nerve inflammatory responses. Our previo...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章,评审


    authors: Liu CH,Yang MH,Zhang GZ,Wang XX,Li B,Li M,Woelfer M,Walter M,Wang L

    更新日期:2020-02-12 00:00:00

  • High-salt diet does not boost neuroinflammation and neurodegeneration in a model of α-synucleinopathy.

    abstract:AIM:Pre-clinical studies in models of multiple sclerosis and other inflammatory disorders suggest that high-salt diet may induce activation of the immune system and potentiate inflammation. However, high-salt diet constitutes a common non-pharmacological intervention to treat autonomic problems in synucleinopathies suc...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Heras-Garvin A,Refolo V,Reindl M,Wenning GK,Stefanova N

    更新日期:2020-01-24 00:00:00

  • 5, 8, 11, 14-eicosatetraynoic acid suppresses CCL2/MCP-1 expression in IFN-γ-stimulated astrocytes by increasing MAPK phosphatase-1 mRNA stability.

    abstract:BACKGROUND:The peroxisome proliferator-activated receptor (PPAR)-α activator, 5,8,11,14-eicosatetraynoic acid (ETYA), is an arachidonic acid analog. It is reported to inhibit up-regulation of pro-inflammatory genes; however, its underlying mechanism of action is largely unknown. In the present study, we focused on the ...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Lee JH,Kim H,Woo JH,Joe EH,Jou I

    更新日期:2012-02-18 00:00:00

  • Alteration of colonic excitatory tachykininergic motility and enteric inflammation following dopaminergic nigrostriatal neurodegeneration.

    abstract:BACKGROUND:Parkinson's disease (PD) is frequently associated with gastrointestinal (GI) symptoms, including constipation and defecatory dysfunctions. The mechanisms underlying such disorders are still largely unknown, although the occurrence of a bowel inflammatory condition has been hypothesized. This study examined t...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Pellegrini C,Fornai M,Colucci R,Tirotta E,Blandini F,Levandis G,Cerri S,Segnani C,Ippolito C,Bernardini N,Cseri K,Blandizzi C,Haskó G,Antonioli L

    更新日期:2016-06-13 00:00:00

  • Mannose-binding lectin-associated serine protease 2 (MASP-2) contributes to poor disease outcome in humans and mice with pneumococcal meningitis.

    abstract:BACKGROUND:Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the pro-inflammatory response in the subarachnoid space. The complement system, wh...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Kasanmoentalib ES,Valls Seron M,Ferwerda B,Tanck MW,Zwinderman AH,Baas F,van der Ende A,Schwaeble WJ,Brouwer MC,van de Beek D

    更新日期:2017-01-03 00:00:00

  • NLRP3 inflammasome as a potential treatment in ischemic stroke concomitant with diabetes.

    abstract::The NLRP3 (nucleotide-binding oligomerization domain-like receptor [NLR] family pyrin domain-containing 3) inflammasome is a member of the NLR family of innate immune cell sensors. These are crucial regulators of cytokine secretions, which promote ischemic cell death and insulin resistance. This review summarizes rece...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章,评审


    authors: Hong P,Gu RN,Li FX,Xiong XX,Liang WB,You ZJ,Zhang HF

    更新日期:2019-06-07 00:00:00

  • Transcription factor myocyte enhancer factor 2D regulates interleukin-10 production in microglia to protect neuronal cells from inflammation-induced death.

    abstract:BACKGROUND:Neuroinflammatory responses have been recognized as an important aspect in the pathogenesis of Parkinson's disease (PD). Transcriptional regulation plays a critical role in the process of inflammation. Transcription factor myocyte enhancer factor 2D (MEF2D) is identified as a central factor in transmission o...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Yang S,Gao L,Lu F,Wang B,Gao F,Zhu G,Cai Z,Lai J,Yang Q

    更新日期:2015-02-20 00:00:00

  • Tick-borne encephalitis virus induces chemokine RANTES expression via activation of IRF-3 pathway.

    abstract:BACKGROUND:Tick-borne encephalitis virus (TBEV) is one of the most important flaviviruses that targets the central nervous system (CNS) and causes encephalitides in humans. Although neuroinflammatory mechanisms may contribute to brain tissue destruction, the induction pathways and potential roles of specific chemokines...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Zhang X,Zheng Z,Liu X,Shu B,Mao P,Bai B,Hu Q,Luo M,Ma X,Cui Z,Wang H

    更新日期:2016-08-30 00:00:00

  • The contribution of activated astrocytes to Aβ production: implications for Alzheimer's disease pathogenesis.

    abstract:BACKGROUND:β-Amyloid (Aβ) plays a central role in Alzheimer's disease (AD) pathogenesis. Neurons are major sources of Aβ in the brain. However, astrocytes outnumber neurons by at least five-fold. Thus, even a small level of astrocytic Aβ production could make a significant contribution to Aβ burden in AD. Moreover, act...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Zhao J,O'Connor T,Vassar R

    更新日期:2011-11-02 00:00:00

  • Neuroprotective effects of bilobalide on cerebral ischemia and reperfusion injury are associated with inhibition of pro-inflammatory mediator production and down-regulation of JNK1/2 and p38 MAPK activation.

    abstract:BACKGROUND:Mitogen-activated protein kinase (MAPK) signaling pathways are implicated in inflammatory and apoptotic processes of cerebral ischemia and reperfusion (I/R) injury. Hence, MAPK pathways represent a promising therapeutic target. Exploring the full potential of inhibitors of MAPK pathways is a useful therapeut...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Jiang M,Li J,Peng Q,Liu Y,Liu W,Luo C,Peng J,Li J,Yung KK,Mo Z

    更新日期:2014-09-26 00:00:00

  • Antagonist of the neurokinin-1 receptor curbs neuroinflammation in ex vivo and in vitro models of Lyme neuroborreliosis.

    abstract:BACKGROUND:Lyme neuroborreliosis (LNB) can affect both the peripheral (PNS) and the central nervous systems (CNS); it is caused by the spirochete Borrelia burgdorferi. The neuropeptide substance P (SP) is an important mediator of both neuroinflammation and blood-brain barrier dysfunction, through its NK1 receptor. Incr...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Martinez AN,Ramesh G,Jacobs MB,Philipp MT

    更新日期:2015-12-30 00:00:00

  • Effects of anti-inflammatory vagus nerve stimulation on the cerebral microcirculation in endotoxinemic rats.

    abstract:BACKGROUND:In sepsis syndromes the severity of the inflammation triggers microvascular dysfunction and early organ failure. We studied the effects of anti-inflammatory vagus nerve stimulation on the cerebral microcirculatory integrity in an endotoxinemic rat model. METHODS:In both control and endotoxinemic (5 mg/kg li...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Mihaylova S,Killian A,Mayer K,Pullamsetti SS,Schermuly R,Rosengarten B

    更新日期:2012-07-25 00:00:00

  • Electroacupuncture attenuates cognition impairment via anti-neuroinflammation in an Alzheimer's disease animal model.

    abstract:BACKGROUND:Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive loss of cognitive abilities and memory leading to dementia. Electroacupuncture (EA) is a complementary alternative medicine approach, applying an electrical current to acupuncture points. In clinical and animal studies, EA ...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Cai M,Lee JH,Yang EJ

    更新日期:2019-12-13 00:00:00

  • Cortisol-induced immune suppression by a blockade of lymphocyte egress in traumatic brain injury.

    abstract:BACKGROUND:Acute traumatic brain injury (TBI) represents one of major causes of mortality and disability in the USA. Neuroinflammation has been regarded both beneficial and detrimental, probably in a time-dependent fashion. METHODS:To address a role for neuroinflammation in brain injury, C57BL/6 mice were subjected to...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Dong T,Zhi L,Bhayana B,Wu MX

    更新日期:2016-08-25 00:00:00

  • Neurofilament levels, disease activity and brain volume during follow-up in multiple sclerosis.

    abstract:BACKGROUND:There is a need for clinically useful biomarkers of disease activity in clinically isolated syndrome (CIS) and relapsing remitting MS (RRMS). The aim of this study was to assess the correlation between neurofilament light chain (NFL) in cerebrospinal fluid (CSF) and serum and the relationship between NFL and...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Håkansson I,Tisell A,Cassel P,Blennow K,Zetterberg H,Lundberg P,Dahle C,Vrethem M,Ernerudh J

    更新日期:2018-07-18 00:00:00

  • Increased interleukin-1β levels following low dose MDMA induces tolerance against the 5-HT neurotoxicity produced by challenge MDMA.

    abstract:BACKGROUND:Preconditioning is a phenomenon by which tolerance develops to injury by previous exposure to a stressor of mild severity. Previous studies have shown that single or repeated low dose MDMA can attenuate 5-HT transporter loss produced by a subsequent neurotoxic dose of the drug. We have explored the mechanism...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Mayado A,Torres E,Gutierrez-Lopez MD,Colado MI,O'Shea E

    更新日期:2011-11-24 00:00:00

  • Functional characteristics of Th1, Th17, and ex-Th17 cells in EAE revealed by intravital two-photon microscopy.

    abstract:BACKGROUND:T helper (Th) 17 cells are a highly plastic subset of T cells, which in the context of neuroinflammation, are able to acquire pathogenic features originally attributed to Th1 cells (resulting in so called ex-Th17 cells). Thus, a strict separation between the two T cell subsets in the context of experimental ...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Loos J,Schmaul S,Noll TM,Paterka M,Schillner M,Löffel JT,Zipp F,Bittner S

    更新日期:2020-11-26 00:00:00

  • Infiltrating T lymphocytes reduce myeloid phagocytosis activity in synucleinopathy model.

    abstract:BACKGROUND:Synucleinopathies comprise a group of neurodegenerative diseases associated with abnormal accumulation of α-synuclein. One of the key factors that contribute to the progression of synucleinopathies is neuroinflammation. However, the role of lymphocytes in synucleinopathies like Parkinson's disease (PD) remai...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Sommer A,Fadler T,Dorfmeister E,Hoffmann AC,Xiang W,Winner B,Prots I

    更新日期:2016-06-30 00:00:00

  • A role for DNA-dependent activator of interferon regulatory factor in the recognition of herpes simplex virus type 1 by glial cells.

    abstract:BACKGROUND:The rapid onset of potentially lethal neuroinflammation is a defining feature of viral encephalitis. Microglia and astrocytes are likely to play a significant role in viral encephalitis pathophysiology as they are ideally positioned to respond to invading central nervous system (CNS) pathogens by producing k...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Furr SR,Chauhan VS,Moerdyk-Schauwecker MJ,Marriott I

    更新日期:2011-08-12 00:00:00

  • Role of the indoleamine-2,3-dioxygenase/kynurenine pathway of tryptophan metabolism in behavioral alterations in a hepatic encephalopathy rat model.

    abstract:BACKGROUND:This study aims to explore the role of indoleamine-2,3-dioxygenase (IDO)/kynurenine (KYN) pathway of tryptophan (TRY) metabolism in behavioral alterations observed in hepatic encephalopathy (HE) rats. METHODS:Expression levels of proinflammatory cytokines were tested by QT-PCR and ELISA, levels of IDOs were...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Jiang X,Xu L,Tang L,Liu F,Chen Z,Zhang J,Chen L,Pang C,Yu X

    更新日期:2018-01-04 00:00:00

  • Prevention of methamphetamine-induced microglial cell death by TNF-α and IL-6 through activation of the JAK-STAT pathway.

    abstract:BACKGROUND:It is well known that methamphetamine (METH) is neurotoxic and recent studies have suggested the involvement of neuroinflammatory processes in brain dysfunction induced by misuse of this drug. Indeed, glial cells seem to be activated in response to METH, but its effects on microglial cells are not fully unde...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Coelho-Santos V,Gonçalves J,Fontes-Ribeiro C,Silva AP

    更新日期:2012-07-06 00:00:00

  • Expression of tumor necrosis factor-α and interleukin-1β genes in the cochlea and inferior colliculus in salicylate-induced tinnitus.

    abstract:BACKGROUND:Changes in the gene expressions for tumor necrosis factor-α (TNF-α) and/or interleukin-1β (IL-1β) during tinnitus have not been previously reported. We evaluated tinnitus and mRNA expression levels of TNF-α, IL-1β, and N-methyl D-aspartate receptor subunit 2B (NR2B) genes in cochlea and inferior colliculus (...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Hwang JH,Chen JC,Yang SY,Wang MF,Chan YC

    更新日期:2011-04-09 00:00:00

  • Blast traumatic brain injury and serum inflammatory cytokines: a repeated measures case-control study among U.S. military service members.

    abstract:BACKGROUND:There is a paucity of human data on exposure to blast traumatic brain injury (bTBI) and the corresponding systemic cytokine immune response at later time points (i.e., months, years) post-injury. METHODS:We conducted a repeated measures, case-control study, examining associations of serum levels of pro- and...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Rusiecki J,Levin LI,Wang L,Byrne C,Krishnamurthy J,Chen L,Galdzicki Z,French LM

    更新日期:2020-01-13 00:00:00

  • Curcumin attenuates acute inflammatory injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway in experimental traumatic brain injury.

    abstract:BACKGROUND:Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to substantial neuronal damage and behavioral impairment, and Toll-like receptor 4 (TLR4) is an important mediator of thiscascade. In the current study, we tested the hypothesis that curcumin, a phytochemical compound with po...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Zhu HT,Bian C,Yuan JC,Chu WH,Xiang X,Chen F,Wang CS,Feng H,Lin JK

    更新日期:2014-03-27 00:00:00

  • Astrocytic expression of HIV-1 viral protein R in the hippocampus causes chromatolysis, synaptic loss and memory impairment.

    abstract:BACKGROUND:HIV-infected individuals are at an increased risk of developing neurological abnormalities. HIV induces neurotoxicity by host cellular factors and individual viral proteins. Some of these proteins including viral protein R (Vpr) promote immune activation and neuronal damage. Vpr is known to contribute to cel...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Torres L,Noel RJ Jr

    更新日期:2014-03-22 00:00:00

  • Metalloprotease Adam10 suppresses epilepsy through repression of hippocampal neuroinflammation.

    abstract:BACKGROUND:Mice with pilocarpine-induced temporal lobe epilepsy (TLE) are characterized by intense hippocampal neuroinflammation, a prominent pathological hallmark of TLE that is known to contribute to neuronal hyperexcitability. Recent studies indicate that Adam10, a member of a disintegrin and metalloproteinase domai...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Zhu X,Li X,Zhu M,Xu K,Yang L,Han B,Huang R,Zhang A,Yao H

    更新日期:2018-08-04 00:00:00