Hélène Hirbec

Hélène Hirbec
Université de Montpellier | UM1 · Institut de Génomique Fonctionnelle (IGF)

About

68
Publications
4,426
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Publications

Publications (68)
Article
Full-text available
Ependymal cells reside in the adult spinal cord and display stem cell properties in vitro. They proliferate after spinal cord injury and produce neurons in lower vertebrates but predominantly astrocytes in mammals. The mechanisms underlying this glial-biased differentiation remain ill-defined. We addressed this issue by generating a molecular resou...
Preprint
Full-text available
Background: Research in recent years firmly established that microglial cells play an important role in the pathogenesis of Alzheimer's disease (AD). In parallel, a series of studies showed that, under both homeostatic and pathological conditions, microglia are a heterogeneous cell population. In AD, amyloid-b (Ab) plaque-associated microglia (PAM)...
Preprint
Full-text available
Background: Research in recent years firmly established that microglial cells play an important role in the pathogenesis of Alzheimer's disease (AD). In parallel, a series of studies showed that, under both homeostatic and pathological conditions, microglia are a heterogeneous cell population. In AD, amyloid-b (Ab) plaque-associated microglia (PAM)...
Preprint
Ependymal cells reside in the adult spinal cord around the central canal and have stem cell properties in vitro. They rapidly activate and proliferate after spinal cord injury, constituting a source of new cells. They produce neurons and glial cells in lower vertebrates but they mainly generate glial cells in mammals. The mechanisms underlying thei...
Article
Full-text available
L’exécution des fonctions cérébrales requiert des interactions optimales entre les neurones et les différents types de cellules gliales (astrocytes, microglies et oligodendrocytes). Le domaine de la gliobiologie, qui s’intéresse aux cellules gliales, est en pleine expansion. Les innovations techniques permettent désormais d’aborder des questions bi...
Article
Microglia, the resident immune cells of the brain, have recently emerged as key players in Alzheimer Disease (AD) pathogenesis, but their roles in AD remain largely elusive and require further investigation. Microglia functions are readily altered when isolated from their brain environment, and microglia reporter mice thus represent valuable tools...
Article
Development, physiological functions, and pathologies of the brain depend on tight interactions between neurons and different types of glial cells, such as astrocytes, microglia, oligodendrocytes, and oligodendrocyte precursor cells. Assessing the relative contribution of different glial cell types is required for the full understanding of brain fu...
Chapter
A century ago, Pío del Río-Hortega discovered that microglial cells are endowed with remarkable dynamic and plastic capabilities. The real-time plasticity of microglia could be revealed, however, only during the last 15 years with the development of new transgenic animal models and new molecular and functional analysis methods. Phenotyping microgli...
Article
Full-text available
Microglia are the resident macrophages of the central nervous system. They play key roles in brain development, and physiology during life and aging. Equipped with a variety of molecular sensors and through the various functions they can fulfill, they are critically involved in maintaining the brain’s homeostasis. In Alzheimer disease (AD), microgl...
Article
Full-text available
Microglial cells have a double life as the immune cells of the brain in times of stress but have also specific physiological functions in homeostatic conditions. In pathological contexts, microglia undergo a phenotypic switch called “reaction” that promotes the initiation and the propagation of neuro-inflammation. Reaction is complex, molecularly h...
Article
Full-text available
Over the last decade, microglia have been acknowledged to be key players in central nervous system (CNS) under both physiological and pathological conditions. They constantly survey the CNS environment and as immune cells, in pathological contexts, they provide the first host defense and orchestrate the immune response. It is well recognized that u...
Article
Full-text available
Neurons have inherent competence to regrow following injury, although not spontaneously. Spinal cord injury (SCI) induces a pronounced neuroinflammation driven by resident microglia and infiltrating peripheral macrophages. Microglia are the first reactive glial population after SCI and participate in recruitment of monocyte-derived macrophages to t...
Data
Specific microgial transcript over-expression after SCI in CX3CR1+/eGFP mice. Bar graphs displaying specific over-expression of microglia-specific transcripts at different stages after HS (A). Values are actual fold change. Bar graphs indicating up-regulation of Serpina3n transcript expressions in microglia at different time-point after HS and FT S...
Data
Induction of neural development pathways in microglia after SCI. Gene ontology pathway map analysis displaying the induction of neural development pathway in microglia after SCI. Thermometers indicate deregulated genes (red: up-regulated; blue: down-regulated). Interactions between objects: green (positive or activation); red (negative or inhibitio...
Data
Database of differential expression comparison of activated microglia RNA-Seq data relative to non-injured control microglia at 72 h, 1 and 2 weeks after hemisection and full transection injuries.
Data
Specific microglial eGFP expression in CX3CR1+/eGFP mice spinal cord. Schematic drawing of longitudinal spinal cords from either non-injured control or following FT. The red square illustrates the lesion site and reference frames display on the field of views. Confocal micrographs showing microglial eGFP expression in non-injured CX3CR1+/eGFP mice...
Data
Flow cytometry analysis. Representative flow cytometry analysis dot plots displaying control (A) and eGFPhigh-expressing microglia profiles from non-injured (B) as well as after HS (C) and FT SCI (D). Surrounded areas, designed as “P4” represent sorted cells that correspond to the eGFPhigh-expressing cells further analyzed using RNAseq. The X- and...
Data
Increased IBA1 reactivity 3 months after SCI in Microcebus murinus. Bright field micrographs displaying IBA1-positive microglia rostral (A–C), within (D–F) and caudal (G–I) to the lesion site at 3 months following spinal cord hemisection in Microcebus murinus. Note similar to BRCA1 immunostaining adjacent sections stained with IBA1 displayed identi...
Data
Database of the expression level of cellular markers (microglia, neuronal, astrocyte and oligodendrocyte). Differentially expressed genes amongst these cellular markers, data relative to non-injured control microglia at 72 h, 1 and 2 weeks after hemisection and full transection injuries. FC, Fold change; FDR, false discovery rate.
Data
Microglia responses after SCI are time-dependent irrespective of lesion severity. Schematic diagram displaying the multiple comparisons carried out to analyze deregulated genes in microglia at multiple time-points after HS and FT SCI (A). Table illustrating the number of deregulated transcripts in each comparisons (B). Note that no deregulated gene...
Data
Pathway analysis of differentially expressed genes in activated microglia after hemisection and full transection injuries.
Article
Full-text available
Kainic acid (KA) is routinely used to elicit status epilepticus (SE) and epileptogenesis. Among the available KA administration protocols, intranasal instillation (IN) remains understudied. Dosages of KA were instilled IN in mice. Racine Scale and Video-EEG were used to assess and quantify SE onset. Time spent in SE and spike activity was quantifie...
Article
Full-text available
The NMDAR glutamate receptor subtype mediates various vital physiological neuronal functions. However, its excessive activation contributes to neuronal damage in a large variety of acute and chronic neurological disorders. NMDAR antagonists thus represent promising therapeutic tools that can counteract NMDARs' overactivation. Channel blockers are o...
Article
Within the central nervous system, functions of the ATP-gated receptor-channel P2X4 (P2X4R) are still poorly understood, yet P2X4R activation in neurons and microglia coincides with high or pathological neuronal activities. In this study, we investigated the potential involvement of P2X4R in microglial functions in a model of kainate (KA)-induced s...
Article
Full-text available
Prostaglandin E2 (PGE2) is a key mediator of inflammation and contributes to pain hypersensitivity by promoting sensory neurons hyperexcitability. PGE2 synthesis results from activation of a multi-step enzymatic cascade that includes cyclooxygenases (COXs), the main targets of non-steroidal anti-inflammatory drugs (NSAIDs). Although NSAIDs are wide...
Article
Full-text available
The scaffolding postsynaptic density-95/disks large/zonula occludens-1 (PDZ) domain-containing protein melanoma differentiation associated gene-9 (MDA-9)/syntenin is a tandem PDZ protein overexpressed in human melanoma, and breast and gastric cancer cells. MDA-9/syntenin affects cancer cell motility and invasion through distinct biochemical and sig...
Article
Although it is commonly stated that phencyclidine is an antagonist at ionotropic glutamate receptors, there has been little measure of its potency on other receptors in brain tissue. Although we previously reported that phencyclidine stimulated cloned-dopamine D2Long and D2Short receptors, others reported that phencyclidine did not stimulate D2 rec...
Article
Full-text available
The annual meeting of the French Ion Channels Society, held on the Mediterranean coast of France, is aimed at gathering the international scientific community working on various aspects of ion channels. In this report of the 19th edition of the meeting, held in September 2008, we summarize selected symposia on aspects of the ion channel field from...
Article
Over-stimulation of NMDA receptors (NMDARs) is involved in many neurodegenerative disorders. Thus, developing safe NMDAR antagonists is of high therapeutic interest. GK11 is a high affinity uncompetitive NMDAR antagonist with low intrinsic neurotoxicity, shown to be promising for treating CNS trauma. In the present study, we investigated the molecu...
Article
Syntenin is a approximately 33 kDa scaffolding protein that we have shown previously to bind to kainate receptor subunits via a PDZ interaction. Here we show that syntenin has a tightly regulated developmental profile in neurons and is most abundant in the period of intense growth and synapse formation and stabilization. There is extensive colocali...
Article
The worldwide proliferation of mobile phones raises the question of the effects of 900-MHz electromagnetic fields (EMF) on the brain. Using a head-only exposure device in the rat, we showed that a 15-min exposure to 900-MHz pulsed microwaves at a high brain-averaged power of 6 W/kg induced a strong glial reaction in the brain. This effect, which su...
Article
Prenatal infection constitutes an important risk factor for brain injury, in both premature and full-term infants. Unfortunately, as the mechanisms involved are far from understood, no therapeutic strategy emerges to prevent the damage. We tested the hypothesis that administration of lipopolysaccharide (LPS) to gravid female rats enhanced glutamate...
Article
Kainate receptors have recently been shown to be involved in synaptic transmission, to regulate transmitter release and to mediate synaptic plasticity in different regions of the CNS. However, very little is known about endogenous mechanisms that can control native kainate receptor signalling. In this study we have found that GluR5-containing kaina...
Article
We identified four PDZ domain-containing proteins, syntenin, PICK1, GRIP, and PSD95, as interactors with the kainate receptor (KAR) subunits GluR5(2b,) GluR5(2c), and GluR6. Of these, we show that both GRIP and PICK1 interactions are required to maintain KAR-mediated synaptic function at mossy fiber-CA3 synapses. In addition, PKC alpha can phosphor...
Article
TCP and its derivative gacyclidine (+/- GK11) are high-affinity non-competitive antagonists of N-methyl-D-aspartate (NMDA) receptors (NMDARs) and as such exhibit significant neuroprotective properties. These compounds also bind with a low affinity to binding sites whose pharmacological profiles are different from that of NMDARs. With the intention...
Article
Full-text available
Using sequence homology searches, yeast two-hybrid assays and glutathione S-transferase (GST)-pull-down approaches we have identified a series of glutamate receptor subunits that interact differentially with the PDZ proteins GRIP, PICK1, and syntenin. GST-pull-down experiments identified more interactions than detected by yeast two-hybrid assays. W...
Article
Gacyclidine is a non-competitive NMDA receptor antagonist with potent neuroprotective properties. However, we have previously demonstrated that gacyclidine enantiomers [(-) and (+)GK11] interact with other ('non-NMDA') binding sites which may play a role in the lower self-neurotoxicity of this compound relative to the other NMDA receptor antagonist...
Article
Gacyclidine, a channel blocker of N-methyl-D-aspartate receptors (NMDAR), exhibits potent neuroprotective properties and a low self-neurotoxicity. Preventing its interaction with NMDARs we demonstrate, through the use of its enantiomers, that gacyclidine also interacts with other ('non-NMDA') binding sites. The autoradiographic study showed that th...
Article
Gacyclidine is a new phencyclidine derivative with neuroprotective properties. Tritiated gacyclidine and its enantiomers bind to NMDA receptors with binding parameters similar to those of other non-competitive NMDA receptor antagonists. The (-)enantiomer, (-)GK11, exhibits an affinity (2.5 nM) similar to that of dizocilpine (MK-801), while the (+)e...
Article
Congeners of the potent dopamine (DA) re-uptake inhibitor 1-[1-(2-benzo[b]thiophenyl)cyclohexyl]piperidine (BTCP) are unexpectedly able to bind in the rat cerebellum, although this structure is devoid of dopaminergic nerve endings. In line with previous studies the hypothesis that they bind to low affinity PCP sites labelled with [3H]TCP in the rat...
Article
Gacyclidine (cis(pip/me)-1-[1-(2-thienyl)-2-methylcyclohexyl]piperidine) is a TCP derivative, which exhibits potent neuroprotective properties against glutamate-induced neurotoxicity in vitro and in vivo. In order to better understand gacyclidine pharmacological properties, the binding parameters of its enantiomers ((−) and (+)[]GK11) were determin...
Article
Gacyclidine (1-[1-(2-thienyl)-2-methylcyclohexyl]piperidine), the racemate of (+)-and (-)-GK11, exhibits potent neuroprotective properties due to its antagonism at the NMDA receptor. In its tritiated form, gacyclidine showed a binding distribution similar to that of NMDA receptors in the rat brain. With membrane preparations, the (-)-enantiomer of...

Questions

Question (1)
Question
Hello,
Has anyone tried to use the ExpressArt ® NANO Kit from Amptec with input in the range of 500 pg to 1 ng?
The kit is intended for input from 1-700 ng but my samples are more in the 500-1000 pg range.
Cheers

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