LSD1 cooperates with CTIP2 to promote HIV-1 transcriptional silencing.

Microglial cells are the main HIV-1 targets in the central nervous system (CNS) and constitute an important reservoir of latently infected cells. Establishment and persistence of these reservoirs rely on the chromatin structure of the integrated proviruses. We have previously demonstrated that the cellular cofactor CTIP2 forces heterochromatin formation and HIV-1 gene silencing by recruiting HDAC and HMT activities at the integrated viral promoter.

Mapping of endogenous morphine-like compounds in the adult mouse brain: Evidence of their localization in astrocytes and GABAergic cells.

Endogenous morphine, morphine-6-glucuronide, and codeine, which are structurally identical to vegetal alkaloids, can be synthesized by mammalian cells from dopamine. However, the role of brain endogenous morphine and its derivative compounds is a matter of debate, and knowledge about its distribution is lacking. In this study, by using a validated antibody, we describe a precise mapping of endogenous morphine-like compounds (morphine and/or its glucuronides and/or codeine) in the mouse brain.

Processing of chromogranins/secretogranin in patients with diabetic retinopathy.

Aims: Inflammation has been linked to the development of diabetic retinopathy (DR). Chromogranins A, B (CgA, CgB) and secretogranin II (SgII), are prohormones overexpressed in inflammatory diseases. The present study was conducted to evaluate the presence and processing of these prohormones in the vitreous of patients with DR (DV), compared with nondiabetic vitreous (NDV).

Abnormal nociception and opiate sensitivity of STOP null mice exhibiting elevated levels of the endogenous alkaloid morphine.

Background: Mice deficient for the stable tubule only peptide (STOP) display altered dopaminergic neurotransmission associated with severe behavioural defects including disorganized locomotor activity. Endogenous morphine, which is present in nervous tissues and synthesized from dopamine, may contribute to these behavioral alterations since it is thought to play a role in normal and pathological neurotransmission.

Results: In this study, we showed that STOP null brain structures, including cortex, hippocampus, cerebellum and spinal cord, contain high endogenous morphine amounts.

[Molecular basis of HIV-1 latency - Part II: HIV-1 reactivation and therapeutic implications].

The latent HIV-1 reservoirs established early during infection present a major obstacle for virus eradication. Complete eradication of the virus from infected patients may require a purge of the reservoirs. Since the development of a HIV-1 vaccine is not achieved, and therefore remains a major challenge for the immunologists, future direction towards an effective curative therapy for HIV-1 infection will rely on the development of original therapeutic strategies which take into account latency, chronic replication and accessibility to tissue-sanctuary.

CDKL5 is a brain MeCP2 target gene regulated by DNA methylation.

Rett syndrome and its "early-onset seizure" variant are severe neurodevelopmental disorders associated with mutations within the MECP2 and the CDKL5 genes. Antidepressants and drugs of abuse induce the expression of the epigenetic factor MeCP2, thereby influencing chromatin remodeling. We show that increased MeCP2 levels resulted in the repression of Cdkl5 in rat brain structures in response to cocaine, as well as in cells exposed to serotonin, or overexpressing MeCP2.

[Molecular basis of HIV-1 latency - part I: physiology of HIV-1 latency].

The introduction of the highly active antiretroviral therapy (HAART) in 1996 has greatly extended survival and raised hopes for the eradication of HIV-1. Unfortunately, the optimism declined by revealing the existence of latent HIV-1 reservoirs in cells targeted by the virus. The long-lived HIV-1 reservoirs constitute a major obstacle to the eradication of HIV-1.

Inhibition of histone deacetylases in rats self-administering cocaine regulates lissencephaly gene-1 and reelin gene expression, as revealed by microarray technique.

Injection of the histone deacetylase inhibitor trichostatin A (TsA) to rats has been shown to decrease their motivation to self-administer cocaine. In the present study, we investigated alterations in gene expression patterns in the anterior cingulate cortex and nucleus accumbens of rats self-administering cocaine and treated with TsA. Using oligonucleotide microarrays, we identified 722 probe sets in the cortex and 136 probe sets in the nucleus accumbens that were differentially expressed between vehicle and TsA-treated rats that self-administered cocaine.

A single acute pharmacological dose of γ-hydroxybutyrate modifies multiple gene expression patterns in rat hippocampus and frontal cortex.

γ-Hydroxybutyrate (GHB) is a natural brain neuromodulator that has its own enzymatic machinery for synthesis and degradation, release, and transport systems and several receptors that belong to the G protein-coupled receptor (GPCR) family. Targeting of this system with exogenous GHB is used in therapy to induce sleep and anesthesia and to reduce alcohol withdrawal syndrome. GHB is also popular as a recreational drug for its anxiolytic and mild euphoric effects.

Endogenous morphine levels are increased in sepsis: a partial implication of neutrophils.

Background: Mammalian cells synthesize morphine and the respective biosynthetic pathway has been elucidated. Human neutrophils release this alkaloid into the media after exposure to morphine precursors. However, the exact role of endogenous morphine in inflammatory processes remains unclear.

Catestatin, an endogenous chromogranin A-derived peptide, inhibits in vitro growth of Plasmodium falciparum.

Catestatin, an endogenous peptide derived from bovine chromogranin A, and its active domain cateslytin display powerful antimicrobial activities. We have tested the activities of catestatin and other related peptides on the growth of Plasmodium falciparum in vitro. Catestatin inhibits growth of the chloroquine-sensitive strain of P.

Cocaine self-administration alters the expression of chromatin-remodelling proteins; modulation by histone deacetylase inhibition.

Injection of the histone deacetylases inhibitor trichostatin A to rats has been shown to decrease the reinforcing properties of cocaine. In the present study, we investigated alterations in gene expression patterns in the anterior cingulate cortex, caudate-putamen and nucleus accumbens of rats self-administering cocaine and treated with trichostatin A. As recent studies highlighted the importance of chromatin remodelling in the regulation of gene transcription in neurons, we studied the expression of Mecp2 and of several histone deacetylases.

The antimicrobial peptides derived from chromogranin/secretogranin family, new actors of innate immunity.

Chromogranins/secretogranins are members of the granin family present in secretory vesicles of nervous, endocrine and immune cells. In chromaffin cells, activation of nicotinic cholinergic receptors induces the release, with catecholamines, of bioactive peptides resulting from a natural processing. During the past decade, our laboratory has characterized new antimicrobial chromogranin-derived peptides in the secretions of stimulated bovine chromaffin cells.

Neuropilin-2 acts as a modulator of Sema3A-dependent glioma cell migration.

Semaphorin 3A (Sema3A) is a secreted guidance molecule initially described in the nervous system. This protein is able to control axon growth but also effects on endothelial cells migration. Here, we report that Sema3A acts as a chemorepellent factor for the rat C6 glioma cells and three different human glioma cell lines.

HIV-1 regulation of latency in the monocyte-macrophage lineage and in CD4+ T lymphocytes.

The introduction in 1996 of the HAART raised hopes for the eradication of HIV-1. Unfortunately, the discovery of latent HIV-1 reservoirs in CD4+ T cells and in the monocyte-macrophage lineage proved the optimism to be premature. The long-lived HIV-1 reservoirs constitute a major obstacle to the eradication of HIV-1.

Characterization of human and bovine phosphatidylethanolamine-binding protein (PEBP/RKIP) interactions with morphine and morphine-glucuronides determined by noncovalent mass spectrometry.

Background: The phosphatidylethanolamine-binding protein (PEBP/RKIP), initially found to bind phosphatidylethanolamine (PE), has been shown to be associated with morphine derivatives. Our recent study on bovine primary chromaffin cells showed that inside secretory granules, PEBP is noncovalently associated to endogenous morphine-6-glucuronide (M6G), a highly analgesic morphine metabolite. During stress, M6G-PEBP complexes may be released into circulation to target peripheral opioid receptors.

Pharmacological doses of gamma-hydroxybutyrate (GHB) potentiate histone acetylation in the rat brain by histone deacetylase inhibition.

Several small chain fatty acids, including butyrate, valproate, phenylbutyrate and its derivatives, inhibit several HDAC activities in the brain at a several hundred micromolar concentration. Gamma-hydroxy-butyrate (GHB), a natural compound found in the brain originating from the metabolism of GABA, is structurally related to these fatty acids. The average physiological tissue concentration of GHB in the brain is below 50 microM, but when GHB is administered or absorbed for therapeutic or recreative purposes, its concentration reaches several hundred micromolars.

A PKC-dependent recruitment of MMP-2 controls semaphorin-3A growth-promoting effect in cortical dendrites.

There is increasing evidence for a crucial role of proteases and metalloproteinases during axon growth and guidance. In this context, we recently described a functional link between the chemoattractive Sema3C and Matrix metalloproteinase 3 (MMP3). Here, we provide data demonstrating the involvement of MMP-2 to trigger the growth-promoting effect of Sema3A in cortical dendrites.

Two chromogranin a-derived peptides induce calcium entry in human neutrophils by calmodulin-regulated calcium independent phospholipase A2.

Background: Antimicrobial peptides derived from the natural processing of chromogranin A (CgA) are co-secreted with catecholamines upon stimulation of chromaffin cells. Since PMNs play a central role in innate immunity, we examine responses by PMNs following stimulation by two antimicrobial CgA-derived peptides.

Methodology/principal Findings: PMNs were treated with different concentrations of CgA-derived peptides in presence of several drugs.

Injection of the neuropeptide CNP into dopaminergic rat brain areas decreases alcohol intake.

Alcohol administration is known to alter several brain functions and behaviors in humans and in laboratory animals. One of the targets of ethanol is the mesocorticolimbic dopaminergic reward pathway. We used the "alcohol deprivation effect" test as a rat model of alcohol craving and relapse.

Histone deacetylase inhibitors decrease cocaine but not sucrose self-administration in rats.

Regulation of gene expression is known to contribute to the long-term adaptations taking place in response to drugs of abuse. Recent studies highlighted the regulation of gene transcription in neurons by chromatin remodeling, a process in which posttranslational modifications of histones play a major role. To test the involvement of epigenetic regulation on drug-reinforcing properties, we submitted rats to the cocaine operant self-administration paradigm.

Serum concentration of chromogranin A at admission: an early biomarker of severity in critically ill patients.

Background: Chromogranin A (CGA), a stress marker released with catecholamines by the adrenal medulla, has never been associated with acute inflammation in critically ill patients.

Aim: To determine evidence for a link between serum concentration of CGA, biomarkers of inflammation, and outcome inpatients admitted with or without the systemic inflammatory response syndrome (SIRS).

Methods: At admission, we measured in 53 patients and 14 healthy controls the serum concentrations of CGA,procalcitonin, and C-reactive protein.

Prognostic value of chromogranin A at admission in critically ill patients: a cohort study in a medical intensive care unit.

Background: Risk assessments of patients should be based on objective variables, such as biological markers that can be measured routinely. The acute response to stress causes the release of catecholamines from the adrenal medulla accompanied by chromogranin A (CGA). To date, no study has evaluated the prognostic value of CGA in critically ill intensive care unit patients.