Gene expression profiling of meningiomas: current status after a decade of microarray-based transcriptomic studies

Purpose This article provides a review of the transcriptomic expression profiling studies that have been performed on meningiomas so far. We discuss some future prospects and challenges ahead in the field of gene expression profiling. Methods We performed a systematic search in the PubMed and EMBASE databases in May 2010 using the following search terms alone or in combination: “meningioma”, “microarray analysis”, “oligonucleotide array sequence analysis”, or “gene expression profiling”. Only original research articles in English that had used RNA hybridized to high-resolution microarray chips to generate gene expression profiles were included. Results We identified 13 articles matching the inclusion criteria. All studies had been performed during the last decade. Conclusions The main results of the studies can be grouped in three categories: (1) several groups have identified meningioma-specific genes and genes associated with the three WHO grades, and the main histological subtypes of grade I meningiomas; (2) one publication has shown that the general transcription profile of samples of all WHO grades differs in vivo and in vitro; (3) one report provides evidence that microarray technology can be used in an automated fashion to classify tumors. Due to lack of consensus on how microarray data are presented, possible general trends found across the studies are difficult to extract. This could obstruct the discovery of important genes and pathways universally involved in meningioma biology

Co-localization and regulation of basic fibroblast growth factor and arginine vasopressin in neuroendocrine cells of the rat and human brain

<p>Abstract</p> <p>Background</p> <p>Adult rat hypothalamo-pituitary axis and choroid plexus are rich in basic fibroblast growth factor (FGF2) which likely has a role in fluid homeostasis. Towards this end, we characterized the distribution and modulation of FGF2 in the human and rat central nervous system. To ascertain a functional link between arginine vasopressin (AVP) and FGF2, a rat model of chronic dehydration was used to test the hypothesis that FGF2 expression, like that of AVP, is altered by perturbed fluid balance.</p> <p>Methods</p> <p>Immunohistochemistry and confocal microscopy were used to examine the distribution of FGF2 and AVP neuropeptides in the normal human brain. In order to assess effects of chronic dehydration, Sprague-Dawley rats were water deprived for 3 days. AVP neuropeptide expression and changes in FGF2 distribution in the brain, neural lobe of the pituitary and kidney were assessed by immunohistochemistry, and western blotting (FGF2 isoforms).</p> <p>Results</p> <p>In human hypothalamus, FGF2 and AVP were co-localized in the cytoplasm of supraoptic and paraventricular magnocellular neurons and axonal processes. Immunoreactive FGF2 was associated with small granular structures distributed throughout neuronal cytoplasm. Neurohypophysial FGF2 immunostaining was found in axonal processes, pituicytes and Herring bodies. Following chronic dehydration in rats, there was substantially-enhanced FGF2 staining in basement membranes underlying blood vessels, pituicytes and other glia. This accompanied remodeling of extracellular matrix. Western blot data revealed that dehydration increased expression of the hypothalamic FGF2 isoforms of ca. 18, 23 and 24 kDa. In lateral ventricle choroid plexus of dehydrated rats, FGF2 expression was augmented in the epithelium (Ab773 as immunomarker) but reduced interstitially (Ab106 immunostaining).</p> <p>Conclusions</p> <p>Dehydration altered FGF2 expression patterns in AVP-containing magnocellular neurons and neurohypophysis, as well as in choroid plexus epithelium. This supports the involvement of centrally-synthesized FGF2, putatively coupled to that of AVP, in homeostatic mechanisms that regulate fluid balance.</p

Day / night variation of tryptophan hydroxylase and serotonin N-acetyltransferase mRNA levels in the ovine pineal gland and retina

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Differential expression of the multidrug-resistance associated proteins ABCb1 and ABCc1 between blood-brain interfaces.

Cerebral homeostasis results from the presence of the protective blood-brain and blood-cerebrospinal fluid barriers located respectively at the brain capillary endothelium and the choroid plexus epithelium. ABCb1 (Pgp) and ABCc1 (Mrp1) transporters are two major proteins of neuroprotection whose localization and functional significance at both barriers remain partly unsettled. We conducted a comparative analysis of their relative protein content between the two blood-brain interfaces. Microvessels and choroid plexuses located in the fourth and lateral ventricles were isolated from developing and adult rat brains, and whole homogenates were submitted to quantitative Western blot analysis by using standard curves generated from one of the samples. In adult, choroid plexus-associated Pgp content was less than 0.5% of the level in microvessels, whereas Mrp1 content in microvessels was 4% of that in the fourth ventricle choroid plexus. Pgp but not Mrp1 was enriched in microvessels over parenchyma. In choroid plexuses, Mrp1 displayed a basolateral epithelial localization, and reached its high adult protein level, early during postnatal development. In postnatal as in adult microvessels, Pgp localization appeared luminal. However, by contrast to Mrp1, the level of this transporter increased 4.6-fold between 9-day-old and adult animals. Western blot analysis of human samples confirmed the mirror image of Pgp and Mrp1 expression between the two barriers. We conclude that there are major differences in the mechanisms by which blood-brain interfaces fulfill their neuroprotective functions. The data also highlight the significance of the neuroprotective function of the choroid plexus during brain maturation, when the microvasculature is still developing

Serotoninergic control of the activity and expression of glial GABA transporters in the rat cerebellum.

International audienceGamma-Aminobutyric acid (GABA) transporters (GAT-1, GAT-2, and GAT-3) play a key role in the termination of GABA transmission and the regulation of extracellular GABA concentrations. In the present study, pharmacological, cellular, and molecular analyses provide evidence for a modulatory effect of serotoninergic neurons on the activity and expression of glial GABA transporters in the rat cerebellum. Degeneration of serotoninergic neurons after in vivo 5,7-dihydroxytryptamine (5,7-DHT) treatment resulted in a significant decrease (-27%) in [3H]-GABA uptake into cerebellar punches. This decrease probably occurred via inhibition of GAT-2 or GAT-3 activity since their inhibitor, beta-alanine, induced a decrease in [3H]-GABA uptake in punches of sham-operated rats (-28%), but not in punches of 5,7-DHT-treated rats, demonstrating that serotonin terminal degeneration had already impaired the beta-alanine-sensitive component of GABA uptake. In contrast, nipecotic acid, a preferential inhibitor of GAT-1, induced comparable decreases in [3H]-GABA uptake comparable in punches of 5,7-DHT (-38%) versus sham-operated rats (-37%). The decreases in GAT-1 (-16%), GAT-2 (-34%), and GAT-3 (-32%) mRNA levels after 5,7-DHT treatment (detected by quantitative RT-PCR) are consistent with a serotoninergic control of GABA transporter expression at the transcriptional level. The cellular distribution of GAT-2 and GAT-3 mRNA, shown by in situ hybridization, suggests a glial localization of these transporters in the cerebellum and demonstrated a preferential anatomical localization of GAT-2 mRNA in the granular layer and of GAT-3 mRNA in the deep cerebellar nuclei. A direct serotoninergic control of glial GABA uptake was further demonstrated in vitro since serotonin stimulated the activity and mRNA expression of the GABA transporters in cerebellar astrocyte cultures