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PubMed2003

Early loss of astrocytes after experimental traumatic brain injury.

Neuronal-glial interactions are important for normal brain function and contribute to the maintenance of the brain's extracellular environment. Damage to glial cells following traumatic brain injury (TBI) could therefore be an important contributing factor to brain dysfunction and neuronal injury. We examined the early fate of astrocytes and neurons after TBI in rats. A total of 27 rats were euthanized at 0.5, 1, 2, 4, or 24 h after moderate lateral fluid percussion TBI or after sham TBI. Ipsilateral and contralateral hippocampi were examined in coronal sections from -2.12 to -4.80 mm relative to bregma. Adjacent sections were processed with markers for either astrocytes or degenerating neurons. Astrocytes were visualized using glial fibrillary acidic protein (GFAP) or glutamine synthetase immunohistochemistry. Neuronal degeneration was visualized using Fluoro-Jade (FJ) histofluorescence. At 30 min, there was a significant loss of GFAP immunoreactivity in ipsilateral hippocampal CA3 with some loss of normal astrocyte morphology in the remaining cells. The number of normal staining astrocytes decreased progressively over time with extensive astrocyte loss at 24 h. At 4 h, lightly stained FJ-positive neurons were scattered in the ipsilateral CA3. The intensity and number of FJ-positive neurons progressively increased over time with moderate numbers of degenerating neurons in the ipsilateral hippocampal CA3 evident at 24 h. We conclude that astrocyte loss occurs in the hippocampus early after TBI. The data suggest that loss of supporting glial cell may contribute to subsequent neuronal degeneration.

Animals↗
PubMed2000

Astrocyte differentiation of fetal neuroepithelial cells by interleukin-11 via activation of a common cytokine signal transducer, gp130, and a transcription factor, STAT3.

The interleukin (IL)-6 family cytokines utilize membrane glycoprotein gp130 in common as a critical signal-transducing receptor component. IL-11, a cytokine initially identified as a plasmacytoma growth factor, belongs to this family. We show here that IL-11 and its cognate receptor components are expressed in fetal mouse neuroepithelial cells. We also show that after 4 days of culture with IL-11, cells with typical astrocytic morphologies expressing glial fibrillary acidic protein (GFAP; a marker for astrocytes) come out. This differentiation process is totally dependent on the gp130-mediated signal-transduction pathway involving activation of a latent cytoplasmic transcription factor, STAT3 (for signal transducer and activator of transcription 3), because (a) IL-11-induced astrocyte differentiation is not observed when neuroepithelial cells prepared from gp130-deficient mice were used, (b) stimulation of neuroepithelial cells by IL-11 rapidly induces tyrosine-phosphorylation of STAT3, and (c) transfection of neuroepithelial cells with a dominant-negative form of STAT3 inhibits IL-11-induced activation of the GFAP gene promoter. We have further identified, in the GFAP promoter region, a STAT3 site at which nucleotide substitutions almost completely abolished the IL-11-induced GFAP promoter activation. Taken together, it is suggested that IL-11 contributes to astrocytogenesis in fetal brain via activation of gp130 and STAT3.

Animals↗
PubMed2005

Acute cytotoxic effects of mercuric compounds in cultured astrocytes prepared from cerebral hemisphere and cerebellum of newborn rats.

We investigated acute cytotoxic effects and Hg accumulation after exposure to methylmercury (MeHg) or Hg(2+) in the presence or absence of serum in cultured astrocytes prepared from the cerebral hemisphere or cerebellum of newborn rats. Dose-related changes in viable cell numbers after exposure to mercuric compounds were not different between astrocytes from both regions under the specified conditions. Accumulation of each compound for 3 h was similar in both astrocytes but that for 24 h became different, especially that of Hg(2+). In both astrocytes, susceptibility to the respective compounds was higher in the order of those exposed immediately after, without, and 24 h after changing the serum-containing medium to a serum-free defined medium (SFDM). Accumulation for 3 h was higher in the respective astrocytes exposed to MeHg or Hg(2+) immediately after being maintained in SFDM than in those exposed 24 h after. These results suggest that accumulation of mercuric compounds up to 3 h strongly correlates with susceptibility, at least when maintained in SFDM. Astrocytic morphology changed to a satellite shape after the medium change to SFDM particularly in cerebellar astrocytes but only a few in cerebral hemisphere astrocytes, and it was reverted to a polygonal shape by MeHg but not Hg(2+) at 3 microM. The present results suggest that although some properties such as morphological changes and Hg accumulation are different between cerebral hemisphere and cerebellar astrocytes, these differences are not simply reflected by susceptibility to the acute cytotoxicity of mercuric compounds.

Animals↗
PubMed1996

mu-Opioid receptor-induced Ca2+ mobilization and astroglial development: morphine inhibits DNA synthesis and stimulates cellular hypertrophy through a Ca(2+)-dependent mechanism.

Morphine, a preferential mu-opioid receptor agonist, alters astroglial development by inhibiting cell proliferation and by promoting cellular differentiation. Although morphine affects cellular differentiation through a Ca(2+)-dependent mechanism, few studies have examined whether Ca2+ mediates the effect of opioids on cell proliferation, or whether a particular Ca2+ signal transduction pathway mediates opioid actions. Moreover, it is uncertain whether one or more opioid receptor types mediates the developmental effects of opioids. To address these questions, the present study examined the role of mu-opioid receptors and Ca2+ mobilization in morphine-induced astrocyte development. Morphine (1 microM) and non-morphine exposed cultures enriched in murine astrocytes were incubated in Ca(2+)-free media supplemented with < 0.005, 0.3, 1.0, or 3.0 mM Ca2+ ([Ca2+]o), or in unmodified media containing Ca2+ ionophore (A23187), nifedipine (1 microM), dantrolene (10 microM), thapsigargin (100 nM), or L-glutamate (100 microM) for 0-72 h. mu-Opioid receptor expression was examined immunocytochemically using specific (MOR1) antibodies. Intracellular Ca2+ ([Ca2+]i) was measured by microfluorometric analysis using fura-2. Astrocyte morphology and bromodeoxyuridine (BrdU) incorporation (DNA synthesis) were assessed in glial fibrillary acidic protein (GFAP) immunoreactive astrocytes. The results showed that morphine inhibited astroglial growth by activating mu-opioid receptors. Astrocytes expressed MOR1 immunoreactivity and morphine's actions were mimicked by the selective mu agonist PL017. In addition, morphine inhibited DNA synthesis by mobilizing [Ca2+]i in developing astroglia. At normal [Ca2+]o, morphine attenuated DNA synthesis by increasing [Ca2+]i; low [Ca2+]o (0.3 mM) blocked this effect, while treatment with Ca2+ ionophore or glutamate mimicked morphine's actions. At extremely low [Ca2+]o (< 0.005 mM), morphine paradoxically increased BrdU incorporation. Although opioids can increase [Ca2+]i in astrocytes through several pathways, not all affect DNA synthesis or cellular morphology. Nifedipine (which blocks L-type Ca2+ channels) did not prevent morphine-induced reductions in BrdU incorporation or cellular differentiation, while thapsigargin (which depletes IP3-sensitive Ca2+ stores) severely affected inhibited DNA synthesis and cellular differentiation-irrespective of morphine treatment. However, dantrolene (an inhibitor of Ca(2+)-dependent Ca2+ release) selectively blocked the effects of morphine. Collectively, the findings suggest that opioids suppress astroglial DNA synthesis and promote cellular hypertrophy by inhibiting Ca(2+)-dependent Ca2+ release from dantrolene-sensitive intracellular stores. This implies a fundamental mechanism by which opioids affect central nervous system maturation.

Animals↗
PubMed2005

Connexin43, the major gap junction protein of astrocytes, is down-regulated in inflamed white matter in an animal model of multiple sclerosis.

Both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), its animal model, involve inflammatory attack on central nervous system (CNS) white matter, leading to demyelination and axonal damage. Changes in astrocytic morphology and function are also prominent features of MS and EAE. Resting astrocytes form a network that is interconnected through gap junctions, composed mainly of connexin43 (Cx43) protein. Although astrocytic gap junctional connectivity is known to be altered in many CNS pathologies, little is known about Cx43 expression in inflammatory demyelinating disease. Therefore, we evaluated the expression of Cx43 in spinal cords of EAE mice compared with healthy controls. Lumbar ventral white matter areas were heavily infiltrated with CD11beta-immunoreactive monocytes, and within these infiltrated regions loss of Cx43 immunoreactivity was evident. These regions also showed axonal dystrophy, demonstrated by the abnormally dephosphorylated heavy-chain neurofilament proteins. Astrocytes in these Cx43-depleted lesions were strongly glial fibrillary acidic protein reactive. Significant loss (38%) of Cx43 protein in EAE mouse at the lumbar portion of spinal cords was confirmed by Western blot analysis. Decreased Cx43 transcript level was also observed on cDNA microarray analysis. In addition to changes in Cx43 expression, numerous other genes were altered, including those encoding adhesion and extracellular matrix proteins. Our data support the notion that, in addition to damage of myelinating glia, altered astrocyte connectivity is a prominent feature of inflammatory demyelination.

Animals↗
PubMed1999

Cellular and molecular mechanisms of glial scarring and progressive cavitation: in vivo and in vitro analysis of inflammation-induced secondary injury after CNS trauma.

Post-traumatic cystic cavitation, in which the size and severity of a CNS injury progress from a small area of direct trauma to a greatly enlarged secondary injury surrounded by glial scar tissue, is a poorly understood complication of damage to the brain and spinal cord. Using minimally invasive techniques to avoid primary physical injury, this study demonstrates in vivo that inflammatory processes alone initiate a cascade of secondary tissue damage, progressive cavitation, and glial scarring in the CNS. An in vitro model allowed us to test the hypothesis that specific molecules that stimulate macrophage inflammatory activation are an important step in initiating secondary neuropathology. Time-lapse video analyses of inflammation-induced cavitation in our in vitro model revealed that this process occurs primarily via a previously undescribed cellular mechanism involving dramatic astrocyte morphological changes and rapid migration. The physical process of cavitation leads to astrocyte abandonment of neuronal processes, neurite stretching, and secondary injury. The macrophage mannose receptor and the complement receptor type 3 beta2-integrin are implicated in the cascade that induces cavity and scar formation. We also demonstrate that anti-inflammatory agents modulating transcription via the nuclear hormone receptor peroxisome proliferator-activated receptor-gamma may be therapeutic in preventing progressive cavitation by limiting inflammation and subsequent secondary damage after CNS injury.

Animals↗
PubMed1997

Altered immunoreactivity for glial fibrillary acidic protein in astrocytes within 1 h after cervical spinal cord injury.

One hour after a C2 spinal cord hemisection, there are changes in astrocyte morphology and increased glial fibrillary acidic protein immunoreactivity (GFAP IR) near the site of the lesion. Astrocytes adjacent to the lesion display thick, richly branched processes within 1/2 segment rostral and caudal to the level of hemisection. Astrocytes are also enlarged and immunoreactive in gray matter regions of the spinal cord as far caudal as C4 and rostrally to C1. Sham-operated controls, undergoing a laminectomy and durotomy at C2, but not spinal cord hemisection, also exhibit a strong astroglial reaction within 1 h from C1 to C4. However, controls undergoing only a C2 laminectomy do not demonstrate alterations in GFAP IR compared to non-operated controls. The results of this investigation suggest that spinal cord astrocytes are extremely sensitive to both major as well as minor alterations of their microenvironment. Rapid changes in astroglial morphology, as detected by altered GFAP IR, may play a role in changes in neuronal function following spinal cord injury.

Animals↗
PubMed2000

Time-dependent astroglial changes after gamma knife radiosurgery in the rat forebrain.

OBJECTIVE: Using an experimental rat model and a clinically relevant treatment dose, we performed gamma knife radiosurgery to define the hyperacute radiation effects in normal rat forebrain, the time dependence of the astrocytic reaction, and the participation of astrocytes in the healing process after single-dose gamma radiation injuries. METHODS: Seventy-one rats underwent radiosurgical treatment (4-mm collimator) of the caudate-putamen nucleus (single-fraction maximal dose of 100 Gy) and were killed at times ranging from 3 hours to 90 days. Serial cryostat brain sections were processed with the immunohistochemical avidin-biotin complex technique, using anti-glial fibrillary acidic protein as the primary antibody (to identify astrocytes). RESULTS: Vascular changes, including endothelial hyperplasia and vessel wall thickening, were identified as the earliest postradiation manifestations and continued throughout the observation period. Astrocytes reacted to the radiation injury with hyperplasia and hypertrophy. At earlier time points (3-24 h), proliferation was the predominant reaction. The expression of glial fibrillary acidic protein in the proliferating and hypertrophic astrocytes formed an initial peak in the adjacent corpus callosum 3 days after radiosurgery and peaked within the target site between 14 and 30 days. Astrocytic proliferation and hypertrophy were also observed in distant cortices (frontal, parietal, insular, and piriform cortices) and in the hippocampus. No necrosis was observed less than 30 days after irradiation. By Day 90, necrotic lesions with a mean diameter of 4 mm were identified, with glial scar at their peripheries. Astrocytic morphological features varied according to the distance from the necrosis. The irradiated side contained more glial fibrillary acidic protein-containing cells than did the nonirradiated contralateral side. CONCLUSION: During the early phase after radiation, vasculopathy was the first morphological change and may serve as the initiating factor for subsequent changes. Reactive astrocytes appeared not only at the target site but also in the surrounding regions; the severity of injury was determined by the distance from the target.

Animals↗
PubMedDate not supplied

Two novel cell specific receptor proteins, CRLR and CD 117 in human glial tumors.

OBJECTIVE: CRLR (calcitonin receptor-like receptor) and CD 117, the gene product of c-kit have been shown to be expressed in cells of glial tumors, especially in those with higher malignancy. Here we report the distribution of these peptides in various cellular compartments within those tumors. MATERIAL: Both receptor proteins have been investigated in 95 glial tumor biopsies of different grades. METHODS: Both proteins were visualized by immunohistochemistry with antibodies either commercially available or raised for this purpose. RESULTS: Both receptor peptides can be identified in or around tumor blood vessels. CRLR occurs in some endothelial cells, especially in the microvascular proliferations of glioblastoma multiforme, whereas CD 117 preferentially occurs in cells of the thickened vascular wall within cells of pericyte or fibroblast morphology. Both antigens are found in addition in few neoplastic cells of overt astrocyte morphology. CONCLUSIONS: The occurrence of identical antigens in glial tumor blood vessels and in neighboring tumor cells underlines the common origin of "mesenchymal" and "neuroepithelial" components of such (malignant) glial neoplasms.

Actins↗
PubMed2003

Gabaergic signaling mediates the morphological organization of astrocytes in the adult rat forebrain.

Previous studies have provided evidence that the morphological organization of immature astrocytes is influenced by the inhibitory neuronal transmitter gamma amino-butyric acid (GABA). The present study was designed to determine whether the occurrence of differential organization of mature astrocytes throughout various regions of the adult brain is related to differential GABAergic signaling. For this we first used Western blotting and high-performance liquid chromatography to quantify the levels of the astrocytic protein glial fibrillary acidic protein (GFAP) and GABA, respectively, within the same tissue punches taken from different forebrain regions of the adult rat, as well as immunocytochemistry for GFAP, GABA, or glutamate decarboxylase to visualize the morphological organization of astrocytes and of GABAergic axons in these regions. These data indicate that GFAP and GABA contents are correlated throughout the different forebrain regions analyzed, and that the regions containing the highest densities in GABAergic terminals are those that contain astrocytes exhibiting the highest degree of stellation. Secondly, we chronically increased GABAergic signaling in vivo by the systemic administration of an inhibitor of GABA transaminase or by the intracerebroventricular infusion of muscimol, a potent agonist of GABA(A) receptors. Our data show that in both cases, the GFAP content of the different forebrain regions is significantly augmented, in close association with a marked increase in the number of astrocytic processes and with their degree of branching. Taken together, these data strongly suggest that GABAergic signaling mediates the morphological organization of astrocytes and their expression of GFAP in the adult brain.

4-Aminobutyrate Transaminase↗
PubMed1996

Development of astrocytes and neurons in cultured brain slices from mice lacking connexin43.

Astrocyte and neuronal development was investigated in organotypic brain slice cultures from mouse fetuses with a null mutation in the connexin43 gene. Astrocyte morphology and electrical properties were indistinguishable in null mutant slices and control slices but at 18 days in vitro astrocyte density in the central regions of the null mutant slices was significantly higher than in control slices. Neuronal development assessed morphologically and electrophysiologically appeared normal in the mutant slices. These results suggest that intercellular communication mediated through connexin43 is not essential for the development of astrocytes and neurons but may play a role in regulating astrocytic migration.

Animals↗
PubMed1994

Cytoskeletal alterations in human fetal astrocytes induced by interleukin-1 beta.

Previous studies in this and other laboratories have shown that interleukin-1 beta (IL-1 beta) is a selective and potent activator of human astrocytes with respect to induction of cytokines and hematopoietic growth factors. To study the effect of recombinant human IL-1 beta (rhIL-1 beta) on astrocyte morphology, glial fibrillary acidic protein (GFAP) and vimentin expression, and actin organization, we conducted a systematic survey using dissociated human fetal astrocyte cultures. Within hours of stimulation with IL-1 beta, the majority of astrocytes converted from flat, polygonal cells to small, contracted, highly branched cells. This change in morphology was more striking when serum was eliminated from the medium. Complete dissolution of filamentous actin occurred simultaneously with the change in cell shape, as demonstrated by fluorescein-phalloidin binding. These "activated" astrocytes displayed intense GFAP and vimentin immunoreactivity in the small perikarya and processes. In contrast, the large, flat astrocytes in control cultures showed diffuse pale immunoreactivity for GFAP and vimentin. To quantify the changes in GFAP and vimentin content with IL-1 beta stimulation, densitometric analyses of northern and western blots were performed. Northern blot analysis of IL-1 beta-stimulated astrocytes revealed a transient, marked decrease in steady-state levels of mRNA for GFAP, vimentin, and microtubule-associated protein 4. The decrease in mRNA levels was evident by 4-8 h and fell to the lowest level at 16-24 h (80-98% decrease by densitometry) with partial recovery by 72 h. By immunoblotting, a significant decrease in both GFAP and vimentin protein content was observed after IL-1 beta stimulation. Furthermore, metabolic labeling studies revealed an almost total loss of GFAP synthesis following stimulation with IL-1 beta for 16 h. These observations are consistent with the idea that increases in immunoreactivity were related to factors such as redistribution of epitope, rather than increases in total protein content. We hypothesize that in IL-1 beta-stimulated astrocytes, synthesis of other proteins, e.g., inflammatory cytokines, occurs at the expense of structural proteins and that the decrease in content of cytoskeletal proteins may reflect an "activated" state of astrocytes.

Astrocytes↗
PubMed2003

Upregulation of neuronal nitric oxide synthase in in vitro stellate astrocytes and in vivo reactive astrocytes after electrically induced status epilepticus.

Neuronal nitric oxide synthase (nNOS) is a constitutively expressed and calcium-dependent enzyme. Despite predominantly expressed in neurons, nNOS has been also found in astrocytes, although at lower expression levels. We have studied the regulation of nNOS expression in cultured rat astrocytes from cortex and spinal cord by Western blotting and immunocytochemistry. nNOS was not detectable in cultured astrocytes grown in serum-containing medium (SCM), but was highly expressed after serum deprivation. Accordingly, calcium-dependent NOS activity and both intracellular nitrite levels and nitrotyrosine immunoreactivity after glutamate stimulation were higher in serum-deprived astrocytes than in cells grown in SCM. Serum deprivation induced a modification of astrocytes morphology, from flat to stellate. nNOS up-regulation was also observed in reactive astrocytes of rat hippocampi after electrically induced status epilepticus, as demonstrated by double-labeling experiments. Thus, nNOS upregulation occurs in both in vitro stellate and in vivo reactive astrocytes, suggesting a possible involvement of glial nNOS in neurological diseases characterized by reactive gliosis.

Animals↗
PubMed1994

Astrocytes express insulin-like growth factor-I (IGF-I) and its binding protein, IGFBP-2, during demyelination induced by experimental autoimmune encephalomyelitis.

To assess the distribution of insulin-like growth-factor-related proteins during autoimmune CNS demyelination and remyelination, experimental autoimmune encephalomyelitis was produced by injecting Lewis rats with an emulsion containing guinea pig spinal cord and complete Freund's adjuvant. Tail weakness appeared at 10-12 days and was followed by hind and forelimb weakness. Paraplegia and incontinence were observed in some animals. From 8-40 days postinoculation (dpi), spinal cord sections were used to correlate lesion location and severity with mRNA distributions of insulin-like growth factor I (IGF-I), IGF-binding protein 2 (IGFBP-2), IGF-I-receptor (IGFR-I), glial fibrillary acidic protein (GFAP), and myelin basic protein (MBP). These were determined semiquantitatively by in situ hybridization. Fourteen dpi, there were inflammatory infiltrates and demyelination in both white matter (WM) and grey matter (GM). IGF-I and GFAP mRNAs were increased in these lesions and transcripts encoding myelin basic protein (MBP) were greatly reduced. Large lesions with extensive demyelination were evident in both WM and GM when mRNA levels of GFAP and IGF-I peaked 26 dpi. MBP mRNA levels began increasing 21 dpi and peaked 26 dpi, when a few thin regenerating myelin sheaths were found morphologically. Astrocytes, identified by their morphology and GFAP immunoreactivity, expressed very low levels of IGFBP-2 mRNA and peptide in normal controls; their levels were significantly higher 14 dpi, peaked 26 dpi, and then gradually decreased. Some neurons, as well as oligodendroglia in areas undergoing remyelination, expressed IGFR-I. Although levels of IGF-I, IGFBP-2, and GFAP mRNAs were highest in lesion areas, levels were also elevated around lesions and in some normal-appearing areas of WM and GM 14-40 dpi. The gene expression of both IGF-I and IGFBP-2 by hypertrophic GFAP-positive astrocytes was demonstrated 14-40 dpi by combined in situ hybridization and immunocytochemistry as well as by double immunostaining. Coexpression of IGF-I and IGFBP-2 in the same astrocyte was a frequent finding. Relative increases in both IGF-I, GFAP, IGFBP-2, IGFR-I, and MBP mRNAs peaked at about the same time. This suggests that during lesion progression and recovery, astrocytic expression of IGF-I-related peptides may reduce immune-mediated myelin injury. We also suggest that astrocytic IGFBP-2 in lesions may help target IGF-I to IGFR-I-expressing oligodendrocytes and promote remyelination of demyelinated axons.

Animals↗
PubMed1988

Reactive astrocytes in the morphologic composition of peripheral areas of gliomas.

The participation of reactive astrocytes in the morphologic composition of peripheral areas of 25 gliomas was investigated. Reactive astrocytes were studied by the immunohistochemical demonstration of glial fibrillary acidic protein and vimentin. Reactive astrocytes were more abundant around malignant gliomas than around well-differentiated astrocytomas. They underwent modifications when entrapped within the tumor proliferation and became indistinguishable from tumor astrocytes. Mitoses occurred in both types of cells. Reactive astrocytes did participate in the cell composition of gliomas. They might have contributed to tumor growth. Practically, their occurrence might lead to an erroneous diagnosis when small fragments of tissue are examined.

Astrocytes↗
PubMed2001

A comparison of intermediate filament markers for presumptive astroglia in the developing rat neocortex: immunostaining against nestin reveals more detail, than GFAP or vimentin.

The present study compares the immunopositive elements in the developing rat cortex between the day of birth (P0) and the 18th postnatal day (P18), after immunostaining against nestin, vimentin and glial fibrillary acidic protein (GFAP). Nestin immunostaining revealed more structural details than either vimentin or GFAP, or they together. While vimentin immunostaining preferred radial glia and GFAP preferred astrocytes, nestin immunostaining detected both. Stellate-shaped astrocyte-like cells were already seen at P0 and cells of typical astrocytic morphology were numerous at P3, and were predominating elements from P7, whereas GFAP-immunopositive astrocytes were very scarce even at P7, and became numerous only by P11, when nestin immunopositivity started to disappear. Nestin immunostaining revealed such structures which were not seen in GFAP- or vimentin immunostained sections: cell body-like structures 'hanging' at the end the radial fibers, seeming to divide with their fibers, or having astrocyte-like processes. Nestin immunostaining is therefore highly recommended for studies of the glial architecture in the early post-natal brain development.

Age Factors↗
PubMed1983

Functional receptors for vasoactive intestinal polypeptide in cultured astroglia from neonatal rat brain.

The effects of vasoactive intestinal polypeptide (VIP) were assessed on astroglia cultured from rat CNS. In these cultures VIP (500 nM) promoted the hydrolysis of [3H]glycogen newly synthesized from [3H]glucose. This effect on [3H]glycogen levels was also observed with the structurally related peptide PHI-27 and with other substances which had been demonstrated to promote glycogenolysis in rodent CNS in vitro such as: norepinephrine (NE), serotonin, histamine, adenosine, K+ and dibutyryl cyclic-AMP (dbcAMP). Furthermore, VIP (500 nM) and PHI 27 (500 nM), when applied to astroglial cultures in serum-free medium, displayed marked effects on the morphological appearance of the cell population: they converted the flat cells present in the cultures into cells with typical astrocytic morphology. As previously reported, this effect on the cellular morphology of the cultures was also observed, under identical experimental conditions, after NE and dbcAMP application. These studies demonstrate that cultured rat neonatal astroglia possess receptors for VIP, and suggest that a cyclic AMP accumulation may mediate both the metabolic and morphologic components of this response.

Animals↗
PubMed2005

Heparin structures in FGF-2-dependent morphological transformation of astrocytes.

Fibroblast growth factor-2 (FGF-2) participates in the morphological transformation of astrocytes (stellation) during the formation of glial scars in injured brains. In the current study, we used quantitative morphometric analysis to investigate the structural requirements for heparin's enhancement of FGF-2-induced stellation of cultured cortical astrocytes. Native heparin significantly promoted FGF-2-dependent astrocytic stellation, whereas heparin hexasaccharide inhibited FGF-2-dependent stellation. Furthermore, 2-O-, 6-O-, and N-desulfated heparins were unable to promote FGF-2-dependent stellation. The stellation induced by FGF-2 or by a combination of FGF-2 and native heparin was inhibited by SU5402, an FGF receptor inhibitor. These results demonstrate that the length and sulfated position of heparin are important for its enhancement of FGF-2-dependent astrocyte stellation. In addition, our findings show that heparin oligosaccharides are useful for regulating the FGF-2-dependent astrocytic transformation.

Animals↗