GLAST-CreERT2 mediated deletion of GDNF increases brain damage and exacerbates long-term stroke outcomes after focal ischemic stroke in mouse model.

Abstract:

:Focal ischemic stroke (FIS) is a leading cause of human death. Glial scar formation largely caused by reactive astrogliosis in peri-infarct region (PIR) is the hallmark of FIS. Glial cell-derived neurotrophic factor (GDNF) was originally isolated from a rat glioma cell-line supernatant and is a potent survival neurotrophic factor. Here, using CreERT2 -LoxP recombination technology, we generated inducible and astrocyte-specific GDNF conditional knockout (cKO), that is, GLAST-GDNF-/- cKO mice to investigate the effect of reactive astrocytes (RAs)-derived GDNF on neuronal death, brain damage, oxidative stress and motor function recovery after photothrombosis (PT)-induced FIS. Under non-ischemic conditions, we found that adult GLAST-GDNF-/- cKO mice exhibited significant lower numbers of Brdu+, Ki67+ cells, and DCX+ cells in the dentate gyrus (DG) in hippocampus than GDNF floxed (GDNFf/f ) control (Ctrl) mice, indicating endogenous astrocytic GDNF can promote adult neurogenesis. Under ischemic conditions, GLAST-GDNF-/- cKO mice had a significant increase in infarct volume, hippocampal damage and FJB+ degenerating neurons after PT as compared with the Ctrl mice. GLAST-GDNF-/- cKO mice also had lower densities of Brdu+ and Ki67+ cells in the PIR and exhibited larger behavioral deficits than the Ctrl mice. Mechanistically, GDNF deficiency in astrocytes increased oxidative stress through the downregulation of glucose-6-phosphate dehydrogenase (G6PD) in RAs. In summary, our study indicates that RAs-derived endogenous GDNF plays important roles in reducing brain damage and promoting brain recovery after FIS through neural regeneration and suggests that promoting anti-oxidant mechanism in RAs is a potential strategy in stroke therapy.

journal_name

Glia

journal_title

Glia

authors

Zhang N,Zhang Z,He R,Li H,Ding S

doi

10.1002/glia.23848

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

2395-2414

issue

11

eissn

0894-1491

issn

1098-1136

journal_volume

68

pub_type

杂志文章

相关文献

GLIA文献大全
  • The origin of remyelinating cells in the adult central nervous system: the role of the mature oligodendrocyte.

    abstract::The sequence of events by which new oligodendrocytes are generated in the adult mammalian central nervous system has not been clearly defined. Here we review old evidence that remyelinating cells can arise from the division of mature oligodendrocytes. In addition, we report the results of a tissue culture study compar...

    journal_title:Glia

    pub_type: 杂志文章,评审

    doi:10.1002/glia.440040214

    authors: Wood PM,Bunge RP

    更新日期:1991-01-01 00:00:00

  • Rehabilitative therapies differentially alter proliferation and survival of glial cell populations in the perilesional zone of cortical infarcts.

    abstract::Rehabilitative therapies after stroke are designed to improve remodeling of neuronal circuits and to promote functional recovery. Only very little is known about the underlying cellular mechanisms. In particular, the effects of rehabilitative training on glial cells, which play an important role in the pathophysiology...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20632

    authors: Keiner S,Wurm F,Kunze A,Witte OW,Redecker C

    更新日期:2008-04-01 00:00:00

  • Cell type-specific regulation of major histocompatibility complex (MHC) class I gene expression in astrocytes, oligodendrocytes, and neurons.

    abstract::Mechanisms of major histocompatibility complex (MHC) class I gene regulation in cells of the CNS have been studied in vitro. Astrocytes in primary cultures, but neither oligodendrocytes nor neurons, constitutively expressed cell surface MHC class I molecules. Interferon-gamma (IFN-gamma) treatment led to induction of ...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440080307

    authors: Massa PT,Ozato K,McFarlin DE

    更新日期:1993-07-01 00:00:00

  • Inositol 1,4,5-trisphosphate receptor type 2-independent Ca2+ release from the endoplasmic reticulum in astrocytes.

    abstract::Accumulating evidence indicates that astrocytes are actively involved in the physiological and pathophysiological functions of the brain. Intracellular Ca2+ signaling, especially Ca2+ release from the endoplasmic reticulum (ER), is considered to be crucial for the regulation of astrocytic functions. Mice with genetic ...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.23531

    authors: Okubo Y,Kanemaru K,Suzuki J,Kobayashi K,Hirose K,Iino M

    更新日期:2019-01-01 00:00:00

  • ROCK inhibition with Y27632 activates astrocytes and increases their expression of neurite growth-inhibitory chondroitin sulfate proteoglycans.

    abstract::Inhibition of Rho-kinase (ROCK) with Y27632 stimulates sprouting by injured corticospinal tract and dorsal column tract axons, and accelerates functional recovery. However, regeneration of these axons across the glial scar was not observed. Here we examined the effects of Y27632 treatment on chondroitin sulfate proteo...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20466

    authors: Chan CC,Wong AK,Liu J,Steeves JD,Tetzlaff W

    更新日期:2007-03-01 00:00:00

  • Sphingosine-1-phosphate is released by cerebellar astrocytes in response to bFGF and induces astrocyte proliferation through Gi-protein-coupled receptors.

    abstract::The mitogenic role of sphingosine-1-phosphate (S1P) and its involvement in basic fibroblast growth factor (bFGF)-induced proliferation were examined in primary cultures of cerebellar astrocytes. Exposure to bFGF resulted in a rapid increase of extracellular S1P formation, bFGF inducing astrocytes to release S1P, but n...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20324

    authors: Bassi R,Anelli V,Giussani P,Tettamanti G,Viani P,Riboni L

    更新日期:2006-04-15 00:00:00

  • Innate immunity and neuroinflammation in the CNS: the role of microglia in Toll-like receptor-mediated neuronal injury.

    abstract::Microglia are key players of the immune response in the central nervous system (CNS) and, being the resident innate immune cells, they are responsible for the early control of infections and for the recruitment of cells of the adaptive immune system required for pathogen clearance. The innate and adaptive immune respo...

    journal_title:Glia

    pub_type: 杂志文章,评审

    doi:10.1002/glia.20928

    authors: Lehnardt S

    更新日期:2010-02-01 00:00:00

  • Effect of TPA on aquaporin 4 mRNA expression in cultured rat astrocytes.

    abstract::Aquaporin 4 (AQP4) is a predominant water channel protein in mammalian brains, localized in the astrocyte plasma membrane. The regulation of AQP4 is believed to be important for the homeostasis of water in the brain, but the AQP4 regulatory mechanisms are not yet known. In this study, we investigated the effect of a p...

    journal_title:Glia

    pub_type: 杂志文章

    doi:

    authors: Nakahama K,Nagano M,Fujioka A,Shinoda K,Sasaki H

    更新日期:1999-02-01 00:00:00

  • A novel role of microglial NADPH oxidase in mediating extra-synaptic function of norepinephrine in regulating brain immune homeostasis.

    abstract::Although the peripheral anti-inflammatory effect of norepinephrine (NE) is well documented, the mechanism by which this neurotransmitter functions as an anti-inflammatory/neuroprotective agent in the central nervous system (CNS) is unclear. This article aimed to determine the anti-inflammatory/neuroprotective effects ...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.22801

    authors: Jiang L,Chen SH,Chu CH,Wang SJ,Oyarzabal E,Wilson B,Sanders V,Xie K,Wang Q,Hong JS

    更新日期:2015-06-01 00:00:00

  • Platelet-activating factor induces cell death in cultured astrocytes and oligodendrocytes: involvement of caspase-3.

    abstract::The biologically active lipid metabolite, platelet-activating factor (PAF), is thought to contribute to inflammatory processes and tissue damage in a variety of central nervous system (CNS) injuries. In previous studies, we found that after contusion spinal cord injury, treatment with a PAF antagonist led to significa...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.10065

    authors: Hostettler ME,Knapp PE,Carlson SL

    更新日期:2002-05-01 00:00:00

  • ADAM-10 and ADAM-17 in the inflamed human CNS.

    abstract::Inflammatory demyelinating disorders of the CNS, such as multiple sclerosis (MS), are mediated, at least in part, by various cytokines and proteases. In the present study, we investigated the expression of A disintegrin and metalloproteinase (ADAM)-17, an important sheddase for various proteins, including tumor necros...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.10226

    authors: Kieseier BC,Pischel H,Neuen-Jacob E,Tourtellotte WW,Hartung HP

    更新日期:2003-06-01 00:00:00

  • VEGF as a modulator of the innate immune response in glioblastoma.

    abstract::VEGF is an important factor in tumor vascularization and used as target for anti-angiogenic treatment strategies in glioma. In this study, we demonstrate for the first time that VEGF is a modulator of the innate immune response with suppressive effects on the immunologic and pro-angiogenic function of microglia/macrop...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.23234

    authors: Turkowski K,Brandenburg S,Mueller A,Kremenetskaia I,Bungert AD,Blank A,Felsenstein M,Vajkoczy P

    更新日期:2018-01-01 00:00:00

  • MiR-409-3p and MiR-1896 co-operatively participate in IL-17-induced inflammatory cytokine production in astrocytes and pathogenesis of EAE mice via targeting SOCS3/STAT3 signaling.

    abstract::Th17 cells and interleukin-17 (IL-17) have been found to play an important role in the pathology of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Response to IL-17, reactive astrocytes accompany with immune cells infiltration and axonal damage in MS/EAE. However, the ro...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.23530

    authors: Liu X,Zhou F,Yang Y,Wang W,Niu L,Zuo D,Li X,Hua H,Zhang B,Kou Y,Guo J,Kong F,Pan W,Gao D,Meves JM,Sun H,Xue M,Zhang Q,Wang Y,Tang R

    更新日期:2019-01-01 00:00:00

  • Differential regulation of trophic and proinflammatory microglial effectors is dependent on severity of neuronal injury.

    abstract::Microglial activation has been reported to promote neurotoxicity and also neuroprotective effects. A possible contributor to this dichotomy of responses may be the degree to which proximal neurons are injured. The aim of this study was to determine whether varying the severity of neuronal injury influenced whether mic...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20610

    authors: Lai AY,Todd KG

    更新日期:2008-02-01 00:00:00

  • Gene expression profiling reveals a conserved microglia signature in larval zebrafish.

    abstract::Microglia are the resident macrophages of the brain. Over the past decade, our understanding of the function of these cells has significantly improved. Microglia do not only play important roles in the healthy brain but are involved in almost every brain pathology. Gene expression profiling allowed to distinguish micr...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.23717

    authors: Mazzolini J,Le Clerc S,Morisse G,Coulonges C,Kuil LE,van Ham TJ,Zagury JF,Sieger D

    更新日期:2020-02-01 00:00:00

  • Age-related changes in astrocytic and ependymal cells of the subventricular zone.

    abstract::Neurogenesis persists in the adult subventricular zone (SVZ) of the mammalian brain. During aging, the SVZ neurogenic capacity undergoes a progressive decline, which is attributed to a decrease in the population of neural stem cells (NSCs). However, the behavior of the NSCs that remain in the aged brain is not fully u...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.22642

    authors: Capilla-Gonzalez V,Cebrian-Silla A,Guerrero-Cazares H,Garcia-Verdugo JM,Quiñones-Hinojosa A

    更新日期:2014-05-01 00:00:00

  • Modulation of two functionally distinct Ca2+ stores in astrocytes: role of the plasmalemmal Na/Ca exchanger.

    abstract::Mechanisms that regulate the amount of releasable Ca2+ in intracellular stores of cultured mouse astrocytes were investigated using digital imaging of fura-2 loaded cells. At rest, the cytoplasmic Ca2+ concentration, [Ca2+]cyt, was about 110 nM. In the absence of extracellular Ca2+, cyclopiazonic acid (CPA), an inhibi...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-1136(199604)16:4<296::AID-GLIA2

    authors: Golovina VA,Bambrick LL,Yarowsky PJ,Krueger BK,Blaustein MP

    更新日期:1996-04-01 00:00:00

  • Induction of the genes for Cxcl9 and Cxcl10 is dependent on IFN-gamma but shows differential cellular expression in experimental autoimmune encephalomyelitis and by astrocytes and microglia in vitro.

    abstract::The chemokines CXCL9 and CXCL10 bind to the common receptor CXCR3 and are implicated in the pathogenesis of T-cell-mediated immunity in the central nervous system (CNS). Here we examined the temporal and spatial regulation of the Cxcl9 and Cxcl10 genes in the CNS of mice with myelin oligodendrocyte glycoprotein (MOG)-...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20587

    authors: Carter SL,Müller M,Manders PM,Campbell IL

    更新日期:2007-12-01 00:00:00

  • Immunocytochemical characterization of reactive optic nerve astrocytes and meningeal cells.

    abstract::Regeneration in the adult central nervous system (CNS) is thought to be hampered by the lesion-induced activation of astrocytes and meningeal cells and the consecutive formation of a glial scar. The substrate properties of reactive astrocytes differ significantly from their neonatal counterparts, which promote axon gr...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/(sici)1098-1136(199903)26:1<36::aid-glia4>

    authors: Hirsch S,Bähr M

    更新日期:1999-03-01 00:00:00

  • Neu differentiation factor regulates tau protein and mRNA in cultured neonatal oligodendrocytes.

    abstract::Axonal signals activate myelinogenesis via regulation of the extent to which oligodendrocyte (OLG) processes wrap around the axon. The cytoskeleton in OLG processes is actively involved in myelination and is a putative target for axonal regulation of myelination. The axon-associated neuregulins may regulate the cytosk...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.1079

    authors: LoPresti P,Muma NA,De Vries GH

    更新日期:2001-08-01 00:00:00

  • Hyperpolarization-activated ion currents in cultured rat cortical and spinal cord astrocytes.

    abstract::Hyperpolarization-activated currents were recorded from rat brain cortical and spinal cord astrocytes maintained in culture. Spinal cord astrocytes expressed primarily an inward rectifier potassium current characterized by time-dependent inactivation, a strong dependence on extracellular Na+ and insensitivity to intra...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-1136(199603)16:3<196::AID-GLIA2

    authors: Guatteo E,Stanness KA,Janigro D

    更新日期:1996-03-01 00:00:00

  • Expression of N-methyl D-aspartate receptor subunits in amoeboid microglia mediates production of nitric oxide via NF-κB signaling pathway and oligodendrocyte cell death in hypoxic postnatal rats.

    abstract::The present study was focused on identifying the expression of N-methyl D-aspartate receptor (NMDAR) subunits on activated microglia and to determine their role in the pathogenesis of periventricular white matter damage (PWMD) in neonatal rats following hypoxia. One day old wistar rats were subjected to hypoxia (5% O(...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.21121

    authors: Murugan M,Sivakumar V,Lu J,Ling EA,Kaur C

    更新日期:2011-04-01 00:00:00

  • Astrocytes interact intimately with degenerating motor neurons in mouse amyotrophic lateral sclerosis (ALS).

    abstract::Astrocytic proliferation and hypertrophy (astrogliosis) are associated with neuronal injury. However, neither the temporal nor the spatial relationship between astrocytes and injured neurons is clear, especially in neurodegenerative diseases. We investigated these questions in a mouse amyotrophic lateral sclerosis (AL...

    journal_title:Glia

    pub_type: 杂志文章

    doi:

    authors: Levine JB,Kong J,Nadler M,Xu Z

    更新日期:1999-12-01 00:00:00

  • Acidic pH rapidly increases immunoreactivity of glial fibrillary acidic protein in cultured astrocytes.

    abstract::Neuroepithelial progenitor cells from forebrains of newborn rat pups develop into "mature" astrocytes in an epidermal growth factor-containing medium free of serum (Von Visger et al: Exp Neurol 128:34, 1994). Eight-week-old "mature" astrocyte cultures on poly-L-lysine-coated dishes were exposed to an acidic medium (pH...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440130408

    authors: Oh TH,Markelonis GJ,Von Visger JR,Baik B,Shipley MT

    更新日期:1995-04-01 00:00:00

  • Nitric oxide as a messenger between neurons and satellite glial cells in dorsal root ganglia.

    abstract::Abnormal neuronal activity in sensory ganglia contributes to chronic pain. There is evidence that signals can spread between cells in these ganglia, which may contribute to this activity. Satellite glial cells (SGCs) in sensory ganglia undergo activation following peripheral injury and participate in cellular communic...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.23603

    authors: Belzer V,Hanani M

    更新日期:2019-07-01 00:00:00

  • Neurofibromatosis 1 (NF1) heterozygosity results in a cell-autonomous growth advantage for astrocytes.

    abstract::Individuals with neurofibromatosis 1 (NF1) develop low-grade astrocytomas at an increased frequency. To gain insight into the function of the Nf1 gene product as a growth regulator for astrocytes, we examined mice heterozygous for a targeted Nf1 mutation. In our previous studies, we demonstrated increased numbers of p...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/1098-1136(20010315)33:4<314::aid-glia1030>

    authors: Bajenaru ML,Donahoe J,Corral T,Reilly KM,Brophy S,Pellicer A,Gutmann DH

    更新日期:2001-03-15 00:00:00

  • Patterned distribution of immunoreactive astroglial processes in the striate (V1) cortex of New World monkeys.

    abstract::The possibility of a modular organization of non-neuronal elements was analyzed in the opercular region of the striate neocortex in adult New World monkeys. For this purpose, and in order to follow possible correlations in the general organization of neuronal and astroglial elements, immunocytochemical procedures for ...

    journal_title:Glia

    pub_type: 杂志文章

    doi:

    authors: Colombo JA,Schleicher A,Zilles K

    更新日期:1999-01-01 00:00:00

  • Neuronal dependency of the glycine transporter GLYT1 expression in glial cells.

    abstract::Two membrane-localized transporter proteins (GLYT1 and GLYT2) are responsible for removal of extracellular glycine in the mammalian CNS. Whereas GLYT1 seems to be expressed mainly in glial cells, GLYT2 is neuronal. The highest concentrations of both transporters are found in glycinergic areas of the nervous system. Th...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/(sici)1098-1136(199706)20:2<155::aid-glia7

    authors: Zafra F,Poyatos I,Gimenez C

    更新日期:1997-06-01 00:00:00

  • Oligodendrocyte-specific ceramide galactosyltransferase (CGT) expression phenotypically rescues CGT-deficient mice and demonstrates that CGT activity does not limit brain galactosylceramide level.

    abstract::Galactosylceramide (GalC) is the major sphingolipid of the myelin membrane. Mice lacking GalC due to ceramide galactosyltransferase (CGT) deficiency form unstable and functionally affected myelin and exhibit a progressive demyelination, accompanied by severe motor coordination deficits. In addition to oligodendrocytes...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20230

    authors: Zöller I,Büssow H,Gieselmann V,Eckhardt M

    更新日期:2005-11-15 00:00:00

  • Astrocytic poly(ADP-ribose) polymerase-1 activation leads to bioenergetic depletion and inhibition of glutamate uptake capacity.

    abstract::Poly(ADP-ribose) polymerase-1 (PARP-1) is a ubiquitous nuclear enzyme involved in genomic stability. Excessive oxidative DNA strand breaks lead to PARP-1-induced depletion of cellular NAD(+), glycolytic rate, ATP levels, and eventual cell death. Glutamate neurotransmission is tightly controlled by ATP-dependent astroc...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20936

    authors: Tang KS,Suh SW,Alano CC,Shao Z,Hunt WT,Swanson RA,Anderson CM

    更新日期:2010-03-01 00:00:00