Inhibition of mTOR pathway restrains astrocyte proliferation, migration and production of inflammatory mediators after oxygen-glucose deprivation and reoxygenation.


:Glial scar is a major impediment to axonal regeneration in central nervous system (CNS) disorders. Overcoming this physical and biochemical barrier might be crucial for axonal regeneration and functional compensation during the progression of CNS disorders. The mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase, involved in process of cell proliferation, migration, autophagy and protein synthesis. Rapamycin, an inhibitor of mTOR signaling, can exert neuroprotective effects in several CNS diseases. However, its role in the process of reactive astrogliosis including cell proliferation, migration and cytokine production after cerebral ischemia still remains largely unknown. In this study, we investigated the effects of mTOR blockade in cultured astrocytes exposed to oxygen-glucose deprivation/reoxygenation (OGD/R), a wildly used cellular ischemia model which mimics ideally cerebral ischemia model in vivo. We found that astrocytes became activated after OGD/R, characterized by change of astrocytic morphology, upregulation of GFAP expression, the increase number of Edu positive cells, and accompanied with phosphorylation of mTOR protein and its substrate S6K1. Rapamycin significantly inhibited mTOR signal pathway, suppressed proliferation of astrocytes via modulation of cell cycle progression. Moreover, rapamycin attenuated astrocytic migration and mitigated production of inflammatory factors such as TNF-α and iNOS induced by astrocytes exposed to OGD/R. Taken together, our findings indicated that mTOR blockade by rapamycin attenuates astrocyte migration, proliferation and production of inflammation mediators. We suggest that targeting mTOR pathway in astrocyte activation may represent a potentially new therapeutic strategy against deleterious neurotoxic processes of reactive astrogliosis in CNS disorders such as ischemic stroke.


Neurochem Int


Li CY,Li X,Liu SF,Qu WS,Wang W,Tian DS




Has Abstract


2015-04-01 00:00:00












  • Metabolomic analyses of vigabatrin (VGB)-treated mice: GABA-transaminase inhibition significantly alters amino acid profiles in murine neural and non-neural tissues.

    abstract::The anticonvulsant vigabatrin (VGB; SabrilR) irreversibly inhibits GABA transaminase to increase neural GABA, yet its mechanism of retinal toxicity remains unclear. VGB is suggested to alter several amino acids, including homocarnosine, β-alanine, ornithine, glycine, taurine, and 2-aminoadipic acid (AADA), the latter ...

    journal_title:Neurochemistry international

    pub_type: 杂志文章


    authors: Walters DC,Arning E,Bottiglieri T,Jansen EEW,Salomons GS,Brown MN,Schmidt MA,Ainslie GR,Roullet JB,Gibson KM

    更新日期:2019-05-01 00:00:00

  • Bisperoxovanadium complex promotes dopamine exocytosis in PC12 cells.

    abstract::The effects of the peroxovanadium complex potassium bisperoxo(1,10-phenanthroline)-oxovanadate (bpV[phen]) have been studied on dopamine (DA) exocytosis in PC12 cells. Bisperoxo(1,10-phenanthroline)-oxovanadate does not elicit dopamine secretion in PC12 cells. However, treatment of PC12 cells with 30 microM bpV[phen] ...

    journal_title:Neurochemistry international

    pub_type: 杂志文章


    authors: Bieger S,Morinville A,Maysinger D

    更新日期:2002-04-01 00:00:00

  • Pregnenolone sulfate in the brain: a controversial neurosteroid.

    abstract::Pregnenolone sulfate (PREGS) has been shown, either at high nanomolar or at micromolar concentrations, to increase neuronal activity by inhibiting GABAergic and by stimulating glutamatergic neurotransmission. PREGS is also a potent modulator of sigma type 1 (sigma1) receptors. It has been proposed that these actions o...

    journal_title:Neurochemistry international

    pub_type: 杂志文章,评审


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    更新日期:2008-03-01 00:00:00

  • Melatonin receptors: localization, molecular pharmacology and physiological significance.

    abstract::A pre-requisite to understanding the physiological mechanisms of action of melatonin is the identification of the target sites where the hormone acts. The radioligand 2-[125I]iodo-melatonin has been used extensively to localize binding sites in both the brain and peripheral tissues. In general these binding sites have...

    journal_title:Neurochemistry international

    pub_type: 杂志文章,评审


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  • Structural analogues of ZAPA as GABAA agonists.

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    journal_title:Neurochemistry international

    pub_type: 杂志文章


    authors: Allan RD,Dickenson HW,Johnston GA,Kazlauskas R,Mewett KN

    更新日期:1997-06-01 00:00:00

  • Agonist binding fraction of dopamine D2/3 receptors in rat brain: a quantitative autoradiographic study.

    abstract::There has arisen considerable interest in the study of dopamine D(2/3) agonist binding sites by positron emission tomography (PET), based on the claim that agonist sites represent a functional subset of the total number of sites labeled by more conventional antagonist ligands. To test the basis of this claim, we used ...

    journal_title:Neurochemistry international

    pub_type: 杂志文章


    authors: Minuzzi L,Cumming P

    更新日期:2010-05-01 00:00:00

  • NGF-dependent formation of ruffles in PC12D cells required a different pathway from that for neurite outgrowth.

    abstract::Two signaling pathways, phosphoinositide 3-kinase (PI-3k)/Akt and Ras/MAPK, are major effectors triggered by nerve growth factor (NGF). Rac1, Cdc42 and GSK-3beta are reported to be targets of PI-3k in the signal transduction for neurite outgrowth. Immediately after NGF was added, broad ruffles were observed temporaril...

    journal_title:Neurochemistry international

    pub_type: 杂志文章


    authors: Jin E,Nosaka K,Sano M

    更新日期:2007-07-01 00:00:00

  • Brain edema in diseases of different etiology.

    abstract::Cerebral edema is a potentially life-threatening complication shared by diseases of different etiology, such as diabetic ketoacidosis, acute liver failure, high altitude exposure, dialysis disequilibrium syndrome, and salicylate intoxication. Pulmonary edema is also habitually present in these disorders, indicating th...

    journal_title:Neurochemistry international

    pub_type: 杂志文章,评审


    authors: Adeva MM,Souto G,Donapetry C,Portals M,Rodriguez A,Lamas D

    更新日期:2012-07-01 00:00:00

  • Cell-selective effects of ammonia on glutamate transporter and receptor function in the mammalian brain.

    abstract::Increased brain ammonia concentrations are a hallmark feature of several neurological disorders including congenital urea cycle disorders, Reye's syndrome and hepatic encephalopathy (HE) associated with liver failure. Over the last decade, increasing evidence suggests that hyperammonemia leads to alterations in the gl...

    journal_title:Neurochemistry international

    pub_type: 杂志文章,评审


    authors: Chan H,Butterworth RF

    更新日期:2003-09-01 00:00:00

  • Concerted action of antiepileptic and antidepressant agents to depress spinal neurotransmission: Possible use in the therapy of spasticity and chronic pain.

    abstract::Chronic pain states and epilepsies are common therapeutic targets of voltage-gated sodium channel blockers. Inhibition of sodium channels results in central muscle relaxant activity as well. Selective serotonin reuptake inhibitors are also applied in the treatment of pain syndromes. Here, we investigate the pharmacody...

    journal_title:Neurochemistry international

    pub_type: 杂志文章


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    更新日期:2007-03-01 00:00:00

  • Existence of high and low affinity dinucleotides pentaphosphate-induced calcium responses in individual synaptic terminals and lack of correlation with the distribution of P2X1-7 subunits.

    abstract::Individual analysis of synaptic terminals calcium responses, induced by dinucleotides pentaphosphate, Ap(5)A or Gp(5)G, demonstrates the presence of two main groups considering the concentration required for stimulation. The first group corresponds to those responding to Ap(5)A or Gp(5)G at nanomolar concentration, re...

    journal_title:Neurochemistry international

    pub_type: 杂志文章


    authors: Gómez-Villafuertes R,Sánchez-Nogueiro J,Marín-García P,Miras-Portugal MT

    更新日期:2007-03-01 00:00:00

  • Excessive release of [3H] noradrenaline by veratridine and ischemia in spinal cord.

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    journal_title:Neurochemistry international

    pub_type: 杂志文章


    authors: Sumiya Y,Torigoe K,Gerevich Z,Köfalvi A,Vizi ES

    更新日期:2001-07-01 00:00:00

  • Correlation between rotational behaviors and neurochemical changes associated with damage of rat striatum: Analysis using unilateral microinjection of kainic acid.

    abstract::The correlation between rotational behaviors and neurochemical changes associated with the striatal damage induced by an unilateral microinjection of kainic acid were investigated. Shortly after the unilateral striatal injection of kainic acid, rats exhibited contralateral rotational behaviors, and these changes were ...

    journal_title:Neurochemistry international

    pub_type: 杂志文章


    authors: Kuriyama K,Kurihara E

    更新日期:1982-01-01 00:00:00

  • FAM3A attenuates ER stress-induced mitochondrial dysfunction and apoptosis via CHOP-Wnt pathway.

    abstract::Endoplasmic reticulum (ER) stress is linked to several neurological disorders, and neuronal injury cascades initiated by excessive ER stress are mediated, in part, via mitochondrial dysfunction. In the present study, we identified FAM3A as an important regulator of ER stress-induced cell death in neuronal HT22 cells. ...

    journal_title:Neurochemistry international

    pub_type: 杂志文章


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  • The P2Y14 receptor in the trigeminal ganglion contributes to the maintenance of inflammatory pain.

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    journal_title:Neurochemistry international

    pub_type: 杂志文章


    authors: Lin J,Zhang YY,Liu F,Fang XY,Liu MK,Huang CL,Wang H,Liao DQ,Zhou C,Shen JF

    更新日期:2019-12-01 00:00:00

  • Cytosolic sialidase from the nerve endings of developing rat forebrain.

    abstract::The developmental profile of cytosolic sialidase from the nerve ending and the nerve ending-free compartments of rat forebrain was studied from birth to 150 days. Soluble extracts containing the cytosol from nerve endings and nerve ending-free tissue were separately prepared; the recovery of cytosol in the two extract...

    journal_title:Neurochemistry international

    pub_type: 杂志文章


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  • Effects of nigral dopaminergic lesions and striatal excitotoxin lesions on brain converting enzyme.

    abstract::High levels of angiotensin converting enzyme (ACE) are found in the caudate-putamen (CPu), globus pallidus, entopeduncular nucleus and substantia nigra pars reticulata; these structures were connected by a continuous band of ACE. In order to investigate whether ACE was associated with dopaminergic projections from the...

    journal_title:Neurochemistry international

    pub_type: 杂志文章


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    更新日期:1987-01-01 00:00:00

  • Acylation of myelin proteolipid protein in subcellular fractions of rat brainstem.

    abstract::The acylation of myelin proteolipid protein (PLP) and intermediate protein (IP) was investigated in an in vitro system of tissue slices prepared from actively myelinating rat brainstem. The incorporation of [(3)H]palmitate into the proteins in nine subcellular fractions including myelin and other cellular membranes wh...

    journal_title:Neurochemistry international

    pub_type: 杂志文章


    authors: Konat G,Gantt G,Hogan EL

    更新日期:1986-01-01 00:00:00

  • Disposition of exogenous tritium-labelled GM1lactone in the rat.

    abstract::The disposition of labelled [3H]GM1lactone, the inner ester of ganglioside GM1, was studied in the rat. After i.v. administration [3H]GM1lactone was quickly converted to its corresponding open form most likely by plasma esterases, and then displayed a pharmacokinetic profile identical to [3H]GM1. Following intramuscul...

    journal_title:Neurochemistry international

    pub_type: 杂志文章


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  • GABA and the regulation of serotonin N-acetyltransferase activity in amphibian retina-I. Effects of GABA agonists and antagonists.

    abstract::Retinal melatonin biosynthesis is regulated in part by changes in the activity of serotonin N-acetyltransferase (NAT), which increases at night in dark-adapted retinas, but not in light-exposed retinas. Using an in vitro preparation of Xenopus laevis (African clawed frog) eye cups, we have obtained evidence supporting...

    journal_title:Neurochemistry international

    pub_type: 杂志文章


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  • Metabolism of [1-(13)C)glucose and [2-(13)C]acetate in the hypoxic rat brain..

    abstract::The effects of hypoxia on the metabolism of the central nervous system were investigated in rats submitted to a low oxygen atmosphere (8% O(2); 92% N(2)). [1-(13)C]glucose and [2-(13)C]acetate were used as substrates, this latter being preferentially metabolized by glial cells. After 1-h substrate infusion, the incorp...

    journal_title:Neurochemistry international

    pub_type: 杂志文章


    authors: Chateil J,Biran M,Thiaudière E,Canioni P,Merle M

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  • Repeated exposure to methiopropamine increases dendritic spine density in the rat nucleus accumbens core.

    abstract::Repeated exposure to classical psychomotor stimulants, like amphetamine (AMPH), produces locomotor sensitization and accompanied structural plasticity of dendritic spines in the nucleus accumbens (NAcc). Following our previous report that repeated administration of methiopropamine (MPA), a structural analog to meth-AM...

    journal_title:Neurochemistry international

    pub_type: 杂志文章


    authors: Cai WT,Yoon HS,Lee S,Kim JH

    更新日期:2019-10-01 00:00:00

  • Depletion of intracellular Ca2+ store itself may be a major factor in thapsigargin-induced ER stress and apoptosis in PC12 cells.

    abstract::The mechanisms of intracellular calcium store depletion and store-related Ca(2+) dysregulation in relation to apoptotic cell death in PC12 cells were investigated at physiological temperatures with a leak-resistant fluorescent indicator dye Fura-PE3/AM by a cooled CCD imaging analysis system. Electron microscopic obse...

    journal_title:Neurochemistry international

    pub_type: 杂志文章


    authors: Yoshida I,Monji A,Tashiro K,Nakamura K,Inoue R,Kanba S

    更新日期:2006-06-01 00:00:00

  • Calcium dysregulation in Alzheimer's disease.

    abstract::Alzheimer disease (AD) is the most common form of adult dementia. Its pathological hallmarks are synaptic degeneration, deposition of amyloid plaques and neurofibrillary tangles, leading to neuronal loss. A few hypotheses have been proposed to explain AD pathogenesis. The beta-amyloid (Abeta) and hyperphosphorylated t...

    journal_title:Neurochemistry international

    pub_type: 杂志文章,评审


    authors: Bojarski L,Herms J,Kuznicki J

    更新日期:2008-03-01 00:00:00

  • Hippocampal calcium dyshomeostasis and long-term potentiation in 2-week zinc deficiency.

    abstract::On the basis of abnormal neuropsychological behavior in the open-field test after 2-week zinc deprivation, neurochemical response was examined in young mice fed a zinc-deficient diet for 2 weeks. Serum corticosterone concentration was markedly higher in zinc-deficient mice than in the control mice. Basal signals of in...

    journal_title:Neurochemistry international

    pub_type: 杂志文章


    authors: Takeda A,Yamada K,Tamano H,Fuke S,Kawamura M,Oku N

    更新日期:2008-01-01 00:00:00

  • Protein kinase C-mediated impairment of glutamine outward transport and SN1 transporter distribution by ammonia in mouse cortical astrocytes.

    abstract::SN1, a system N amino acid transporter specific for astrocytes, is mainly responsible for export of newly synthesized L-glutamine from the cells. Astrocytic retention of L-glutamine which plays a critical role in ammonia-induced astrocytic swelling resulting in brain edema, could be tentatively attributed to the impai...

    journal_title:Neurochemistry international

    pub_type: 杂志文章


    authors: Dąbrowska K,Albrecht J,Zielińska M

    更新日期:2018-09-01 00:00:00

  • Intrastriatal kainic acid elicits functional supersensitivity of muscarinic receptors regulating dopamine release.

    abstract::Acetylcholine enhanced in a concentration-dependent way the K(+) (15 mM)-evoked release of [(3)H]dopamine from synaptosomes isolated from rat corpus striatum and prelabeled with the radioactive catecholamine. The concentration-effect curve of ACh obtained in presence of 1.2 mM Ca(2+) was progressively shifted to the l...

    journal_title:Neurochemistry international

    pub_type: 杂志文章


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    更新日期:1987-01-01 00:00:00

  • B vitamins in the nervous system.

    abstract::The coenzyme functions of the B vitamins in intermediatry metabolism are well established; nevertheless, for none of them is it possible to determine precisely the connection between the biochemical lesions associated with deficiency and the neurological consequences. Although there is convincing evidence of a neurosp...

    journal_title:Neurochemistry international

    pub_type: 杂志文章


    authors: Bender DA

    更新日期:1984-01-01 00:00:00

  • Colchicine-binding measurements of tubulin in variously sampled and incubated tissues from the mammalian brain.

    abstract::Tissue preparations from the brain of rats and guinea-pigs were examined for their activity in binding isotopically labelled colchicine, as a measure of their content of tubulin. The amount of binding material extracted into a cold buffered solution was unaffected by keeping tissues at 0 degrees C. It diminished by on...

    journal_title:Neurochemistry international

    pub_type: 杂志文章


    authors: McIlwain H,Poll JD

    更新日期:1983-01-01 00:00:00

  • Caffeinated coffee, decaffeinated coffee, and the phenolic phytochemical chlorogenic acid up-regulate NQO1 expression and prevent H₂O₂-induced apoptosis in primary cortical neurons.

    abstract::Neurodegenerative disorders are strongly associated with oxidative stress, which is induced by reactive oxygen species including hydrogen peroxide (H₂O₂). Epidemiological studies have suggested that coffee may be neuroprotective, but the molecular mechanisms underlying this effect have not been clarified. In this stud...

    journal_title:Neurochemistry international

    pub_type: 杂志文章


    authors: Kim J,Lee S,Shim J,Kim HW,Kim J,Jang YJ,Yang H,Park J,Choi SH,Yoon JH,Lee KW,Lee HJ

    更新日期:2012-04-01 00:00:00