Reactive astrocytes: cellular and molecular cues to biological function

Ridet, Jean‐Luc; Privat, Alain; Malhotra, S. K.; Gage, Fred H.

doi:10.1016/s0166-2236(97)01139-9

Cited by 1,601 publications

(1,263 citation statements)

References 86 publications

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“…Increased levels of GFAP may also indicate astrocyte activation in our cell cultures by chronic CXCL10 treatment. Activated astrocytes are known to produce soluble trophic and growth factors, and immunomodulatory cytokines that enhance the survival of adjacent neurons and glia in the likely attempt to preserve tissue integrity (Liberto et al, 2004;Ridet et al, 1997;Schwartz et al, 1993). Therefore, effects of chronic CXCL10 on hippocampal neurons observed in our studies may also involve in direct pathways through activation of astrocytes and subsequent secretion of growth factors, cytokines and chemokines and act on the neurons.…”

Section: Discussionmentioning

confidence: 76%

Chronic CXCL10 alters the level of activated ERK1/2 and transcriptional factors CREB and NF-κB in hippocampal neuronal cell culture

Bajova

Nelson

Gruol

2008

Journal of Neuroimmunology

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Signal transduction pathways may be important targets of chemokines during neuroinflammation. In the current study, Western blot analyses show that in rat hippocampal neuronal/glial cell cultures chronic CXCL10 increases the level of protein for ERK1/2 as well as for the transcriptional factors CREB and NF-κB. Bcl-2, an anti-apoptotic protein whose expression can be regulated by a pathway involving ERK1/2, CREB and NF-κB, was also increased in the CXCL10 treated cultures. These results implicate a role for ERK1/2, CREB and NF-κB in effects of CXCL10 on hippocampal cells and suggest that chronic CXCL10 may have a protective role during certain neuroinflammatory conditions.

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Section: Discussionmentioning

confidence: 76%

Chronic CXCL10 alters the level of activated ERK1/2 and transcriptional factors CREB and NF-κB in hippocampal neuronal cell culture

Bajova

Nelson

Gruol

2008

Journal of Neuroimmunology

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“…Astrocytes play seminal physiologic roles, so any disturbances likely have pathologic consequences , and they display homeostatic and inflammatory responses in injury. Indeed, the adaptive plasticity of astrocytes is a modulated reaction to different microenvironmental conditions reflecting fluxes in combinations of ''damage signals'' emanating from various cell types (Ridet et al, 1997). The classic responses of astrocytes to inflammatory stimuli are hypertrophy of astrocytic processes and upregulation of intermediate filaments (i.e.…”

Section: Discussionmentioning

confidence: 99%

Oxidative and excitotoxic insults exert differential effects on spinal motoneurons and astrocytic glutamate transporters: Implications for the role of astrogliosis in amyotrophic lateral sclerosis

Zagami

Beart

Wallis

et al. 2008

Glia

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In amyotrophic lateral sclerosis (ALS) non-neuronal cells play key roles in disease etiology and loss of motoneurons via noncell-autonomous mechanisms. Reactive astrogliosis and dysfunctional transporters for L-glutamate [excitatory amino acid transporters, (EAATs)] are hallmarks of ALS pathology. Here, we describe mechanistic insights into ALS pathology involving EAAT-associated homeostasis in response to a destructive milieu, in which oxidative stress and excitotoxicity induce respectively astrogliosis and motoneuron injury. Using an in vitro neuronal-glial culture of embryonic mouse spinal cord, we demonstrate that EAAT activity was maintained initially, despite a loss of cellular viability induced by exposure to oxidative [3-morpholinosydnonimine chloride (SIN-1)] and excitotoxic [(S)-5-fluorowillardiine (FW)] conditions. This homeostatic response of EAAT function involved no change in the cell surface expression of EAAT1/2 at 0.5-4 h, but rather alterations in kinetic properties. Over this time-frame, EAAT1/2 both became more widespread across astrocytic arbors in concert with increased expression of glial fibrillary acidic protein (GFAP), although at 8-24 h there was gliotoxicity, especially with SIN-1 rather than FW. An opposite picture was found for motoneurons where FW, not SIN-1, produced early and extensive neuritic shrinkage and blebbing ( 0.5 h) with somata loss from 2 h. We postulate that EAATs play an early homeostatic and protective role in the pathologic milieu. Moreover, the differential profiles of injury produced by oxidative and excitotoxic insults identify two distinct phases of injury which parallel important aspects of the pathology of ALS. V V C

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“…Persistent changes in spinal astrocytes in chronic pain states-Glial fibrillary acidic protein (GFAP), vimentin and S-100β are the markers that are used most often to identify astrocytes (Ridet et al, 1997). Although astrocytes are not as homogenous as previously thought, GFAP appears to label most astrocytes in the spinal cord.…”

Section: Involvement Of Spinal Astrocytes In Chronic Painmentioning

confidence: 99%

Possible role of spinal astrocytes in maintaining chronic pain sensitization: review of current evidence with focus on bFGF/JNK pathway

et al. 2006

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Although pain is regarded traditionally as neuronally mediated, recent progress shows an important role of spinal glial cells in persistent pain sensitization. Mounting evidence has implicated spinal microglia in the development of chronic pain (e.g. neuropathic pain after peripheral nerve injury). Less is known about the role of astrocytes in pain regulation. However, astrocytes have very close contact with synapses and maintain homeostasis in the extracellular environment. In this review, we provide evidence to support a role of spinal astrocytes in maintaining chronic pain. In particular, cJun N-terminal kinase (JNK) is activated persistently in spinal astrocytes in a neuropathic pain condition produced by spinal nerve ligation. This activation is required for the maintenance of neuropathic pain because spinal infusion of JNK inhibitors can reverse mechanical allodynia, a major symptom of neuropathic pain. Further study reveals that JNK is activated strongly in astrocytes by basic fibroblast growth factor (bFGF), an astroglial activator. Intrathecal infusion of bFGF also produces persistent mechanical allodynia. After peripheral nerve injury, bFGF might be produced by primary sensory neurons and spinal astrocytes because nerve injury produces robust bFGF upregulation in both cell types. Therefore, the bFGF/JNK pathway is an important signalling pathway in spinal astrocytes for chronic pain sensitization. Investigation of signaling mechanisms in spinal astrocytes will identify new molecular targets for the management of chronic pain.

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Reactive astrocytes: cellular and molecular cues to biological function

Cited by 1,601 publications

References 86 publications

Chronic CXCL10 alters the level of activated ERK1/2 and transcriptional factors CREB and NF-κB in hippocampal neuronal cell culture

Chronic CXCL10 alters the level of activated ERK1/2 and transcriptional factors CREB and NF-κB in hippocampal neuronal cell culture

Oxidative and excitotoxic insults exert differential effects on spinal motoneurons and astrocytic glutamate transporters: Implications for the role of astrogliosis in amyotrophic lateral sclerosis

Possible role of spinal astrocytes in maintaining chronic pain sensitization: review of current evidence with focus on bFGF/JNK pathway

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