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Impaired CO2 sensitivity of astrocytes in a mouse model of Rett syndrome.

Rett syndrome, a prototypical neurological disorder caused by loss of function of the transcriptional regulator methyl-CpG-binding protein 2 (MeCP2) gene, is associated with a severely disordered breathing pattern and reduced ventilatory CO2 sensitivity. In a mouse model of Rett syndrome (MeCP2 knockout), re-introduction of the MeCP2 gene selectively in astrocytes rescues normal respiratory phenotype. In the present study we determined whether the metabolic and/or signalling functions of astrocytes are affected by testing the hypotheses that in conditions of MeCP2 deficiency, medullary astrocy…

Acetylation regulates the stability of glutamate carboxypeptidase II protein in human astrocytes.

Glutamate carboxypeptidase II (GCPII) is known to be implicated in brain diseases such as schizophrenia and bipolar disorder, and dramatically increases in prostate cancer. Here, we investigated the regulation of GCPII expression in astrocytes and examined whether GCPII is epigenetically regulated through histone modification. In this study, valproic acid (VPA), a drug used for bipolar disorder and epilepsy and a known histone deacetylase (HDAC) inhibitor was used. We found that acute exposure of VPA for 4-6h increased the GCPII protein level in human astrocyte U87MG cells but did not have a s…

G-protein coupled receptor-evoked glutamate exocytosis from astrocytes: role of prostaglandins.

Astrocytes are highly secretory cells, participating in rapid brain communication by releasing glutamate. Recent evidences have suggested that this process is largely mediated by Ca(2+)-dependent regulated exocytosis of VGLUT-positive vesicles. Here by taking advantage of VGLUT1-pHluorin and TIRF illumination, we characterized mechanisms of glutamate exocytosis evoked by endogenous transmitters (glutamate and ATP), which are known to stimulate Ca(2+) elevations in astrocytes. At first we characterized the VGLUT1-pHluorin expressing vesicles and found that VGLUT1-positive vesicles were a specif…

Astrocytes differentially respond to inflammatory autoimmune insults and imbalances of neural activity.

BACKGROUND: Neuronal activity intimately communicates with blood flow through the blood-brain barrier (BBB) in the central nervous system (CNS). Astrocyte endfeet cover more than 90% of brain capillaries and interact with synapses and nodes of Ranvier. The roles of astrocytes in neurovascular coupling in the CNS remain poorly understood. RESULTS: Here we show that astrocytes that are intrinsically different are activated by inflammatory autoimmune insults and alterations of neuronal activity. In the progression of experimental autoimmune encephalomyelitis (EAE), both fibrous and protoplasmic …

Brain-derived neurotrophic factor interacts with astrocytes and neurons to control respiration.

Respiratory rhythm is generated and modulated in the brainstem. Neuronal involvement in respiratory control and rhythmogenesis is now clearly established. However, glial cells have also been shown to modulate the activity of brainstem respiratory groups. Although the potential involvement of other glial cell type(s) cannot be excluded, astrocytes are clearly involved in this modulation. In parallel, brain-derived neurotrophic factor (BDNF) also modulates respiratory rhythm. The currently available data on the respective roles of astrocytes and BDNF in respiratory control and rhythmogenesis lea…

Induction of cytopathic effect and cytokines in coxsackievirus B3-infected murine astrocytes.

BACKGROUND: Coxsackievirus commonly infects children and occasionally causes severe meningitis and/or encephalitis in the newborn. The underlying mechanism(s) behind the central nervous system pathology is poorly defined. METHODS: It is hypothesized that astrocytes may be involved in inflammatory response induced by CVB3 infection. Here we discuss this hypothesis in the context of CVB3 infection and associated inflammatory response in primary mouse astrocytes. RESULTS: The results showed that coxsackievirus receptor (CAR) was distributed homogeneously on the astrocytes, and that CVB3 could i…

Abnormal glycogen in astrocytes is sufficient to cause adult polyglucosan body disease.

BACKGROUND: A 45-year old woman of Cambodian ethnic background presented with fatal respiratory failure due to a severe diaphragmatic dysfun … PBD) was confirmed by enzymatic and molecular studies. CONCLUSION: Storage of abnormal glycogen in astrocytes is sufficient to cause the leukodystrophy of APBD. Since brain glycogen is almost exclusively metabolized in astrocytes, this observation sheds light on the pathophysiology of APBD. In addition, this is the first report of an APBD patient presenting …

Ultrastructure and electrophysiology of astrocytes differentiated from adult adipose-derived stromal cells.

BACKGROUND: Adipose-derived stromal cell (ADSC) differentiation into neural cells in vitro is becoming widely studied. However, there are few reports on astrocytes following differentiation, and particularly on maturation and electrophysiology. In this study, we used various methods to determine ADSC-derived astrocyte maturity. METHODS: Chemical induction with isobutylmethylxanthine (IBMX) was used to differentiate adult ADSCs into astrocytes followed by hematoxylin-eosin (HE) staining to observe morphology and transmission electron microscopy for cellular ultrastructure assessment. Immunoflu…

S100B modulates growth factors and costimulatory molecules expression in cultured human astrocytes.

S100B is a Ca(2+)-binding protein expressed in the nervous system. Increased levels of S100B in the extracellular space have been detected in several neurological disorders. We investigated the response of human astrocytes to micromolar chronic concentrations of this protein measuring the expression of some costimulatory molecules, such as CD137, CD137-L, CD40, CD40-L, the chemokine RANTES and two growth factors FGF-2 and TGF-β2. Our findings suggest that high levels of S100B in the brain parenchyma may modulate the activation status of astrocytes decreasing their neuroprotective role and modi…

Alexander disease mutant glial fibrillary acidic protein compromises glutamate transport in astrocytes.

Alexander disease (AxD) is a leukodystrophy caused by heterozygous mutations in the gene for glial fibrillary acidic protein, an intermediate filament protein expressed by astrocytes. The mutation causes prominent protein aggregates inside astrocytes; there is also loss of myelin and oligodendrocytes and neuronal degeneration. We show that immunohistochemical staining for glutamate transporter 1, the major brain glutamate transporter expressed primarily in astrocytes suggests decreased levels in the hippocampi of infantile AxD patients. A knock-in mouse model of AxD also shows significant redu…

Valproic acid stimulates clusterin expression in human astrocytes: Implications for Alzheimer's disease.

Clusterin is a secreted molecular chaperone, also called apolipoprotein J. Recent genetic studies have demonstrated that clusterin is a sign … r. In this study, we examined whether valproic acid can induce the expression of clusterin in human astrocytes. Our results demonstrated that valproic acid is a potent inducer of clusterin expression and secretion in human astrocytes at the therapeutical concentrations. Another clinically used HDAC inhibitor, the cancer drug, Vorinostat (SAHA, suberoylanilid …

An excitatory loop with astrocytes contributes to drive neurons to seizure threshold.

Seizures in focal epilepsies are sustained by a highly synchronous neuronal discharge that arises at restricted brain sites and subsequently spreads to large portions of the brain. Despite intense experimental research in this field, the earlier cellular events that initiate and sustain a focal seizure are still not well defined. Their identification is central to understand the pathophysiology of focal epilepsies and to develop new pharmacological therapies for drug-resistant forms of epilepsy. The prominent involvement of astrocytes in ictogenesis was recently proposed. We test here whether …

Effect of resveratrol on gliotransmitter levels and p38 activities in cultured astrocytes.

Accumulating evidence suggests that resveratrol may have beneficial effects against traumatic brain injury. However, its effect on the regulation of extracellular levels of gliotransmitter and on the activation of p38 MAPK in astrocytes is still unknown. We have examined whether resveratrol regulates extracellular levels of gliotransmitter as well as the activation of p38 MAPK in cultured astrocytes before and after stretch injury. The extracellular levels of glutamate, D-/L-serine and D-serine were apparently reduced by 100 μM resveratrol in control astrocyte cultures. The dramatic increase o…

Rett syndrome astrocytes are abnormal and spread MeCP2 deficiency through gap junctions.

MECP2, an X-linked gene encoding the epigenetic factor methyl-CpG-binding protein-2, is mutated in Rett syndrome (RTT) and aberrantly expressed in autism. Most children affected by RTT are heterozygous Mecp2-/+ females whose brain function is impaired postnatally due to MeCP2 deficiency. While prior functional investigations of MeCP2 have focused exclusively on neurons and have concluded the absence of MeCP2 in astrocytes, here we report that astrocytes express MeCP2, and MeCP2 deficiency in astrocytes causes significant abnormalities in BDNF regulation, cytokine production, and neuronal dendr…

Bestrophin-1 encodes for the Ca2+-activated anion channel in hippocampal astrocytes.

In mammalian brain, neurons and astrocytes are reported to express various chloride and anion channels, but the evidence for functional expression of Ca(2+)-activated anion channel (CAAC) and its molecular identity have been lacking. Here we report electrophysiological evidence for the CAAC expression and its molecular identity by mouse Bestrophin 1 (mBest1) in astrocytes of the mouse brain. Using Ca(2+) imaging and perforated-patch-clamp analysis, we demonstrate that astrocytes displayed an inward current at holding potential of -70 mV that was dependent on an increase in intracellular Ca(2+)…

Mice overexpressing chemokine ligand 2 (CCL2) in astrocytes display enhanced nociceptive responses.

Recent findings demonstrate that chemokines, and more specifically CC chemokine ligand 2 (CCL2 or monocyte chemoattractant protein-1), play a major role in pain processing. In the present study, we assess nociceptive responses of mice that overexpressed CCL2 under control of glial fibrillary acidic protein promoter (CCL2 tg). In models of acute nociception CCL2 tg mice demonstrated significantly enhanced nociceptive behavior relative to wild-type controls in responses to both thermal (hot plate) and chemical (formalin test) stimulus modalities. There were no differences in mechanical allodynia

Population differences in elastin maturation in optic nerve head tissue and astrocytes.

PURPOSE: Glaucomatous optic neuropathy is characterized by remodeling of the extracellular matrix with disorganization of elastic fibers in … orescent staining. Elastin and lysyl oxidase mRNA levels and alternative splicing of elastin in ONH astrocytes were investigated by quantitative PCR. Tropoelastin protein expression was assessed by immunoblot analysis. RESULTS: ONHs from AA donors had significantly reduced levels of desmosine compared with those of CAs. In contrast, elastin mRNA and tropoel …

Олигодендроциты внутри астроцитов ("emperipolesis") в белом веществе в болезни Креуцфельдт-Якоб.

Происхождение олигодендроцитов в астроцитах ("эмпериполиз") описано в демиелионирующих повреждениях в случаях множественного склероза, а также в других недемилинирующих расстройствах. Мы обнаружили, что этот вывод был характерен для церебральной белой материи пациентов с болезнью Критцфельдта-Якоба (CJD). Было проведено восемь последовательных вскрытий эпизодической CJD, и в каждом случае серая материя демонстрировала классические гистопатологические особенности CJD. В пяти случаях с длинным клиническим курсом церебральная белая материя была серьезно затронута, и как аксоны, так и миелины были

Совпадение в аннотации оригинала
The occurrence of oligodendrocytes within astrocytes ("emperipolesis") has been described in demyelinating lesions in cases of multiple sclerosis and also in other non-demyelinating disorders. We found that this finding was common in the cerebral white matter of patients with Creutzfeldt-Jakob disease (CJD). Eight consecutive autopsy cases of sporadic CJD we…

JC virus-induced changes in cellular gene expression in primary human astrocytes.

Cell-type-specific transcription of the JC virus (JCV) promoter in glial cells initiates a series of events leading to viral replication in the brain and the development of the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML) in patients with neurologic complications due to infection with human immunodeficiency virus type 1. Here we employed an in vitro infection of primary cultures of human astrocytes to compare the transcriptional profile of cellular genes after JCV infection by using an oligonucleotide-based microarray of 12600 genes. Transcription of nearly 355 …

Effect of toluene inhalation on astrocytes and neurotrophic factor in rat brain.

Toluene, an abused substance in Japan, is a neurotoxic chemical that has been shown to have neurobehavioral and electrophysiological effects. In previous work, both acute and chronic effects of toluene on cells have been studied extensively. However, although glial cells are thought to play an important role in the survival of neurons in the brain, the effect of toluene on glial cell function has not yet been characterized. To elucidate this, the effect of toluene inhalation on astrocytes in rat brain was examined. Toluene exposure (1500 ppm for 4 h on 4-10 days) augmented glial fibrillary aci…