Oligodendrocyte-specific ATF4 inactivation does not influence the development of EAE.


BACKGROUND:Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are inflammatory demyelinating and neurodegenerative diseases of the CNS. Although recent studies suggest the neuroprotective effects of oligodendrocytes in neurodegenerative diseases, it remains unknown whether oligodendrocyte death induced by inflammatory attacks contributes to neurodegeneration in MS and EAE. Upon endoplasmic reticulum (ER) stress, activation of pancreatic ER kinase (PERK) promotes cell survival through induction of activating transcription factor 4 (ATF4) by phosphorylating eukaryotic translation initiation factor 2α (eIF2α). We have generated a mouse model that allows for temporally controlled activation of PERK specifically in oligodendrocytes. Our previous study has demonstrated that PERK activation specifically in oligodendrocytes attenuates EAE disease severity and ameliorates EAE-induced oligodendrocyte apoptosis, demyelination, and axon degeneration, without altering inflammation. METHODS:We determined whether oligodendrocyte-specific PERK activation reduced neuron loss in the CNS of EAE mice using the mouse model that allows for temporally controlled activation of PERK specifically in oligodendrocytes. We further generated a mouse model that allows for inactivation of ATF4 specifically in oligodendrocytes, and determined the effects of ATF4 inactivation in oligodendrocytes on mice undergoing EAE. RESULTS:We showed that protection of oligodendrocytes resulting from PERK activation led to attenuation of neuron loss in the CNS gray matter of EAE mice. Surprisingly, we found that ATF4 inactivation specifically in oligodendrocytes did not alter EAE disease severity and had no effect on oligodendrocyte loss, demyelination, axon degeneration, neuron loss, and inflammation in EAE mice. CONCLUSIONS:These findings suggest the neuroprotective effects of PERK activation in oligodendrocytes in EAE, and rule out the involvement of ATF4 in oligodendrocytes in the development of EAE. These results imply that the protective effects of PERK activation in oligodendrocytes in MS and EAE are not mediated by ATF4.


J Neuroinflammation


Yue Y,Stanojlovic M,Lin Y,Karsenty G,Lin W




Has Abstract


2019-02-01 00:00:00












  • Molecular and cellular neuroinflammatory status of mouse brain after systemic lipopolysaccharide challenge: importance of CCR2/CCL2 signaling.

    abstract:BACKGROUND:Genetic and environmental factors are critical elements influencing the etiology of major depression. It is now accepted that neuroinflammatory processes play a major role in neuropsychological disorders. Neuroinflammation results from the dysregulation of the synthesis and/or release of pro- and anti-inflam...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Cazareth J,Guyon A,Heurteaux C,Chabry J,Petit-Paitel A

    更新日期:2014-07-28 00:00:00

  • Microglial inflammation after chronic spinal cord injury is enhanced by reactive astrocytes via the fibronectin/β1 integrin pathway.

    abstract:BACKGROUND:After spinal cord injury (SCI), glial scarring is mainly formed around the lesion and inhibits axon regeneration. Recently, we reported that anti-β1 integrin antibody (β1Ab) had a therapeutic effect on astrocytes by preventing the induction of glial scar formation. However, the cellular components within the...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Yoshizaki S,Tamaru T,Hara M,Kijima K,Tanaka M,Konno DJ,Matsumoto Y,Nakashima Y,Okada S

    更新日期:2021-01-06 00:00:00

  • Interleukin 18 in the CNS.

    abstract::Interleukin (IL)-18 is a cytokine isolated as an important modulator of immune responses and subsequently shown to be pleiotropic. IL-18 and its receptors are expressed in the central nervous system (CNS) where they participate in neuroinflammatory/neurodegenerative processes but also influence homeostasis and behavio...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章,评审


    authors: Alboni S,Cervia D,Sugama S,Conti B

    更新日期:2010-01-29 00:00:00

  • Caspase-1 has a critical role in blood-brain barrier injury and its inhibition contributes to multifaceted repair.

    abstract:BACKGROUND:Excessive inflammation might activate and injure the blood-brain barrier (BBB), a common feature of many central nervous system (CNS) disorders. We previously developed an in vitro BBB injury model in which the organophosphate paraoxon (PX) affects the BBB endothelium by attenuating junctional protein expres...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Israelov H,Ravid O,Atrakchi D,Rand D,Elhaik S,Bresler Y,Twitto-Greenberg R,Omesi L,Liraz-Zaltsman S,Gosselet F,Schnaider Beeri M,Cooper I

    更新日期:2020-09-09 00:00:00

  • Replication of the association of HLA-B7 with Alzheimer's disease: a role for homozygosity?

    abstract:BACKGROUND:There are reasons to expect an association with Alzheimer's disease (AD) within the HLA region. The HLA-B & C genes have, however, been relatively understudied. A geographically specific association with HLA-B7 & HLA-Cw*0702 had been suggested by our previous, small study. METHODS:We studied the HLA-B & C a...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Lehmann DJ,Barnardo MC,Fuggle S,Quiroga I,Sutherland A,Warden DR,Barnetson L,Horton R,Beck S,Smith AD

    更新日期:2006-12-18 00:00:00

  • The common inflammatory etiology of depression and cognitive impairment: a therapeutic target.

    abstract::Chronic inflammation has been shown to contribute to the development of a wide variety of disorders by means of a number of proposed mechanisms. Depression and cognitive impairment are two such disorders which may share a closely linked inflammatory etiology. The ability of inflammatory mediators to alter the activity...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章,评审


    authors: Allison DJ,Ditor DS

    更新日期:2014-09-02 00:00:00

  • LncGBP9/miR-34a axis drives macrophages toward a phenotype conducive for spinal cord injury repair via STAT1/STAT6 and SOCS3.

    abstract:BACKGROUND:Acute spinal cord injury (SCI) could cause mainly two types of pathological sequelae, the primary mechanical injury, and the secondary injury. The macrophage in SCI are skewed toward the M1 phenotype that might cause the failure to post-SCI repair. METHODS:SCI model was established in Balb/c mice, and the c...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Zhou J,Li Z,Wu T,Zhao Q,Zhao Q,Cao Y

    更新日期:2020-04-28 00:00:00

  • Beneficial effect of TNF-α inhibition on diabetic peripheral neuropathy.

    abstract:BACKGROUND:Tumor necrosis factor-α (TNF-α) is an important inflammatory factor produced by activated macrophages and monocytes and plays an important role in the pathogenesis of diabetic peripheral neuropathy (DPN). To evaluate the effect of TNF-α signaling suppression and the potential of TNF-α in the treatment of DPN...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Shi X,Chen Y,Nadeem L,Xu G

    更新日期:2013-06-04 00:00:00

  • In vivo TSPO and cannabinoid receptor type 2 availability early in post-stroke neuroinflammation in rats: a positron emission tomography study.

    abstract:BACKGROUND:Upregulated levels of 18-kDa translocator proteins (TSPO) and type 2 endocannabinoid receptors (CB2) are considered to reflect different aspects of microglia-related neuroinflammatory responses in the brain. Relative to the increase in the TSPO expression that occurs slightly later during neuroinflammation i...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Hosoya T,Fukumoto D,Kakiuchi T,Nishiyama S,Yamamoto S,Ohba H,Tsukada H,Ueki T,Sato K,Ouchi Y

    更新日期:2017-03-29 00:00:00

  • Human marrow stromal cells reduce microglial activation to protect motor neurons in a transgenic mouse model of amyotrophic lateral sclerosis.

    abstract:BACKGROUND:Human marrow stromal cells (hMSCs) injected intrathecally can effectively increase the lifespan and protect motor neurons in a transgenic mouse model of amyotrophic lateral sclerosis. However, how the transplanted cells exert a neuroprotective effect is still unclear. More recently, the anti-inflammation eff...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Zhou C,Zhang C,Zhao R,Chi S,Ge P,Zhang C

    更新日期:2013-04-30 00:00:00

  • Interactions between inflammatory mediators and corticosteroids regulate transcription of genes within the Kynurenine Pathway in the mouse hippocampus.

    abstract:BACKGROUND:Increased tryptophan metabolism towards the production of kynurenine via indoleamine/tryptophan-2,3-dioxygenases (DOs: Ido1, Ido2, and Tdo2) is strongly associated with the prevalence of major depressive disorder in patients and the induction of depression-like behaviors in animal models. Several studies hav...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Brooks AK,Lawson MA,Smith RA,Janda TM,Kelley KW,McCusker RH

    更新日期:2016-05-03 00:00:00

  • Mossy cell hypertrophy and synaptic changes in the hilus following mild diffuse traumatic brain injury in pigs.

    abstract:BACKGROUND:Each year in the USA, over 2.4 million people experience mild traumatic brain injury (TBI), which can induce long-term neurological deficits. The dentate gyrus of the hippocampus is notably susceptible to damage following TBI, as hilar mossy cell changes in particular may contribute to post-TBI dysfunction. ...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Grovola MR,Paleologos N,Wofford KL,Harris JP,Browne KD,Johnson V,Duda JE,Wolf JA,Cullen DK

    更新日期:2020-01-31 00:00:00

  • Osteopetrotic (op/op) mice have reduced microglia, no Abeta deposition, and no changes in dopaminergic neurons.

    abstract:BACKGROUND:Activation of microglia is a part of the inflammatory response in neurodegenerative diseases but its role in the pathophysiology of these diseases is still unclear. The osteopetrotic (op/op) mouse lacks colony-stimulating factor-1 (CSF-1) and thus has a deficiency in microglia and macrophages. Prior reports ...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Kondo Y,Lemere CA,Seabrook TJ

    更新日期:2007-12-20 00:00:00

  • Cooperative contributions of interferon regulatory factor 1 (IRF1) and IRF8 to interferon-γ-mediated cytotoxic effects on oligodendroglial progenitor cells.

    abstract:BACKGROUND:Administration of exogenous interferon-γ (IFNγ) aggravates the symptoms of multiple sclerosis (MS), whereas interferon-β (IFNβ) is used for treatment of MS patients. We previously demonstrated that IFNγ induces apoptosis of oligodendroglial progenitor cells (OPCs), suggesting that IFNγ is more toxic to OPCs ...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Horiuchi M,Itoh A,Pleasure D,Ozato K,Itoh T

    更新日期:2011-01-24 00:00:00

  • The role of the complement system in traumatic brain injury: a review.

    abstract::Traumatic brain injury (TBI) is an important cause of disability and mortality in the western world. While the initial injury sustained results in damage, it is the subsequent secondary cascade that is thought to be the significant determinant of subsequent outcomes. The changes associated with the secondary injury do...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章,评审


    authors: Hammad A,Westacott L,Zaben M

    更新日期:2018-01-22 00:00:00

  • DHCR24 exerts neuroprotection upon inflammation-induced neuronal death.

    abstract:BACKGROUND:DHCR24, involved in the de novo synthesis of cholesterol and protection of neuronal cells against different stress conditions, has been shown to be selectively downregulated in neurons of the affected brain areas in Alzheimer's disease. METHODS:Here, we investigated whether the overexpression of DHCR24 prot...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Martiskainen H,Paldanius KMA,Natunen T,Takalo M,Marttinen M,Leskelä S,Huber N,Mäkinen P,Bertling E,Dhungana H,Huuskonen M,Honkakoski P,Hotulainen P,Rilla K,Koistinaho J,Soininen H,Malm T,Haapasalo A,Hiltunen M

    更新日期:2017-11-07 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

  • Intracerebral overexpression of miR-669c is protective in mouse ischemic stroke model by targeting MyD88 and inducing alternative microglial/macrophage activation.

    abstract:BACKGROUND:Ischemic stroke is a devastating disease without a cure. The available treatments for ischemic stroke, thrombolysis by tissue plasminogen activator, and thrombectomy are suitable only to a fraction of patients and thus novel therapeutic approaches are urgently needed. The neuroinflammatory responses elicited...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Kolosowska N,Gotkiewicz M,Dhungana H,Giudice L,Giugno R,Box D,Huuskonen MT,Korhonen P,Scoyni F,Kanninen KM,Ylä-Herttuala S,Turunen TA,Turunen MP,Koistinaho J,Malm T

    更新日期:2020-06-19 00:00:00

  • Rab32 connects ER stress to mitochondrial defects in multiple sclerosis.

    abstract:BACKGROUND:Endoplasmic reticulum (ER) stress is a hallmark of neurodegenerative diseases such as multiple sclerosis (MS). However, this physiological mechanism has multiple manifestations that range from impaired clearance of unfolded proteins to altered mitochondrial dynamics and apoptosis. While connections between t...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Haile Y,Deng X,Ortiz-Sandoval C,Tahbaz N,Janowicz A,Lu JQ,Kerr BJ,Gutowski NJ,Holley JE,Eggleton P,Giuliani F,Simmen T

    更新日期:2017-01-23 00:00:00

  • Increased expression of cystine/glutamate antiporter in multiple sclerosis.

    abstract:BACKGROUND:Glutamate excitotoxicity contributes to oligodendrocyte and tissue damage in multiple sclerosis (MS). Intriguingly, glutamate level in plasma and cerebrospinal fluid of MS patients is elevated, a feature which may be related to the pathophysiology of this disease. In addition to glutamate transporters, level...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Pampliega O,Domercq M,Soria FN,Villoslada P,Rodríguez-Antigüedad A,Matute C

    更新日期:2011-06-03 00:00:00

  • Human mesenchymal stem/stromal cells suppress spinal inflammation in mice with contribution of pituitary adenylate cyclase-activating polypeptide (PACAP).

    abstract:BACKGROUND:Adult human mesenchymal stem/stromal cells (hMSCs) from bone marrow have been reported to exhibit beneficial effects on spinal cord injury (SCI). A neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP) is known to decrease neuronal cell death and inflammatory response after ischemia, SCI, ...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Tsumuraya T,Ohtaki H,Song D,Sato A,Watanabe J,Hiraizumi Y,Nakamachi T,Xu Z,Dohi K,Hashimoto H,Atsumi T,Shioda S

    更新日期:2015-02-22 00:00:00

  • 2-arachidonyl glycerol modulates astrocytic glutamine synthetase via p38 and ERK1/2 pathways.

    abstract:BACKGROUND:The glutamine synthetase (GS), an astrocyte-specific enzyme, is involved in lipopolysaccharide (LPS)-induced inflammation which activates the mitogen-activated protein kinase (MAPK) signaling. Endocannabinoid 2-arachidonyl glycerol (2-AG) has been described to serve as an endogenous mediator of analgesia and...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Wang S,Zhang H,Geng B,Xie Q,Li W,Deng Y,Shi W,Pan Y,Kang X,Wang J

    更新日期:2018-08-03 00:00:00

  • Apocynin prevents mitochondrial burdens, microglial activation, and pro-apoptosis induced by a toxic dose of methamphetamine in the striatum of mice via inhibition of p47phox activation by ERK.

    abstract:BACKGROUND:Activation of NADPH oxidase (PHOX) plays a critical role in mediating dopaminergic neuroinflammation. In the present study, we investigated the role of PHOX in methamphetamine (MA)-induced neurotoxic and inflammatory changes in mice. METHODS:We examined changes in mitogen-activated protein kinases (MAPKs), ...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Dang DK,Shin EJ,Nam Y,Ryoo S,Jeong JH,Jang CG,Nabeshima T,Hong JS,Kim HC

    更新日期:2016-01-18 00:00:00

  • Epigenetic suppression of liver X receptor β in anterior cingulate cortex by HDAC5 drives CFA-induced chronic inflammatory pain.

    abstract:BACKGROUND:Liver X receptors (LXRs), including LXRα and LXRβ, are key regulators of transcriptional programs for both cholesterol homeostasis and inflammation in the brain. Here, the modes of action of LXRs and the epigenetic mechanisms regulating LXRβ expression in anterior cingulate cortex (ACC) of chronic inflammato...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Li YJ,Zhang K,Sun T,Wang J,Guo YY,Yang L,Yang Q,Li YJ,Liu SB,Zhao MG,Wu YM

    更新日期:2019-06-29 00:00:00

  • Protective and therapeutic role of 2-carba-cyclic phosphatidic acid in demyelinating disease.

    abstract:BACKGROUND:Multiple sclerosis is a neuroinflammatory demyelinating and neurodegenerative disease of the central nervous system characterized by recurrent and progressive demyelination/remyelination cycles, neuroinflammation, oligodendrocyte loss, demyelination, and axonal degeneration. Cyclic phosphatidic acid (cPA) is...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Yamamoto S,Yamashina K,Ishikawa M,Gotoh M,Yagishita S,Iwasa K,Maruyama K,Murakami-Murofushi K,Yoshikawa K

    更新日期:2017-07-21 00:00:00

  • Diet-induced obesity and low testosterone increase neuroinflammation and impair neural function.

    abstract:BACKGROUND:Low testosterone and obesity are independent risk factors for dysfunction of the nervous system including neurodegenerative disorders such as Alzheimer's disease (AD). In this study, we investigate the independent and cooperative interactions of testosterone and diet-induced obesity on metabolic, inflammator...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Jayaraman A,Lent-Schochet D,Pike CJ

    更新日期:2014-09-16 00:00:00

  • Advanced oxidation protein products induce microglia-mediated neuroinflammation via MAPKs-NF-κB signaling pathway and pyroptosis after secondary spinal cord injury.

    abstract:BACKGROUND:Inflammatory response mediated by oxidative stress is considered as an important pathogenesis of spinal cord injury (SCI). Advanced oxidation protein products (AOPPs) are novel markers of oxidative stress and their role in inflammatory response after SCI remained unclear. This study aimed to investigate the ...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Liu Z,Yao X,Jiang W,Li W,Zhu S,Liao C,Zou L,Ding R,Chen J

    更新日期:2020-03-20 00:00:00

  • Lentivirus-mediated interleukin-1β (IL-1β) knock-down in the hippocampus alleviates lipopolysaccharide (LPS)-induced memory deficits and anxiety- and depression-like behaviors in mice.

    abstract:BACKGROUND:Recent evidence has suggested that peripheral inflammatory responses induced by lipopolysaccharides (LPS) play an important role in neuropsychiatric dysfunction in rodents. Interleukin-1β (IL-1β), a pro-inflammatory cytokine, has been proposed to be a key mediator in a variety of behavioral dysfunction induc...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Li M,Li C,Yu H,Cai X,Shen X,Sun X,Wang J,Zhang Y,Wang C

    更新日期:2017-09-20 00:00:00

  • Oral administration of the KATP channel opener diazoxide ameliorates disease progression in a murine model of multiple sclerosis.

    abstract:BACKGROUND:Multiple Sclerosis (MS) is an acquired inflammatory demyelinating disorder of the central nervous system (CNS) and is the leading cause of nontraumatic disability among young adults. Activated microglial cells are important effectors of demyelination and neurodegeneration, by secreting cytokines and others n...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Virgili N,Espinosa-Parrilla JF,Mancera P,Pastén-Zamorano A,Gimeno-Bayon J,Rodríguez MJ,Mahy N,Pugliese M

    更新日期:2011-11-02 00:00:00

  • Brain-derived neurotrophic factor reduces inflammation and hippocampal apoptosis in experimental Streptococcus pneumoniae meningitis.

    abstract:BACKGROUND:Streptococcus pneumoniae meningitis is a serious inflammatory disease of the central nervous system (CNS) and is associated with high morbidity and mortality rates. The inflammatory processes initiated by recognition of bacterial components contribute to apoptosis in the hippocampal dentate gyrus. Brain-deri...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章


    authors: Xu D,Lian D,Wu J,Liu Y,Zhu M,Sun J,He D,Li L

    更新日期:2017-08-04 00:00:00