A5006822403- Neurotransmitter Receptor Influence on Behavior
- Pancreatic and Hepatic Oncology Research
- Epigenetics and DNA Methylation
- Neuroscience and Neuropharmacology Research
- Adenosine and Purinergic Signaling
- Receptor Mechanisms and Signaling
- Biochemical and Molecular Research
- Cancer Research and Treatments
- Virus-based gene therapy research
- Stress Responses and Cortisol
- Pulmonary Hypertension Research and Treatments
- Nerve injury and regeneration
- Cancer Genomics and Diagnostics
- Cannabis and Cannabinoid Research
- Circadian rhythm and melatonin
- Kruppel-like factors research
- Nicotinic Acetylcholine Receptors Study
- Cancer-related gene regulation
- Neuroendocrine regulation and behavior
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Genetic Associations and Epidemiology
- Pain Mechanisms and Treatments
- Neuroendocrine Tumor Research Advances
- RNA Interference and Gene Delivery
Inserm
2011-2024
Centre de Recherche en Cancérologie de Toulouse
2011-2024
Centre National de la Recherche Scientifique
1996-2024
Université Toulouse III - Paul Sabatier
2010-2024
Université de Toulouse
2010-2024
Hôpital Rangueil
1996-2014
Sorbonne Université
2000-2009
Hôpital Marie Lannelongue
2006
Assistance Publique – Hôpitaux de Paris
2004-2006
Université Paris Cité
2006
Serotonin (5-HT) controls a wide range of biological functions. In the brain, its implication as neurotransmitter and in control behavioral traits has been largely documented. At periphery, modulatory role physiological processes, such cardiovascular function, is still poorly understood. The rate-limiting enzyme 5-HT synthesis, tryptophan hydroxylase (TPH), encoded by two genes, well characterized tph1 gene recently identified tph2 gene. this article, based on study mutant mouse which...
Hypoxia is a well-recognized stimulus for pulmonary blood vessel remodeling and hypertension development. One mechanism that may account these effects the direct action of hypoxia on expression specific genes involved in vascular smooth muscle cell (SMC) proliferation. Previous studies demonstrated serotonin (5-hydroxytryptamine; 5-HT) transporter (5-HTT) mediates mitogenic activity 5-HT SMCs overexpressed during hypoxia. Thus, 5-HT-related increased Here, we report mice deficient 5-HTT...
Abstract By taking up serotonin (5‐hydroxytryptamine, 5‐HT) released in the extracellular space, 5‐HT transporter (5‐HTT) regulates central neurotransmission. Possible adaptive changes neurotransmission knock‐out mice that do not express were investigated with special focus on 1A and 1B receptors. Specific labelling radioligands antibodies, competitive RT‐PCR, showed receptor protein mRNA levels significantly decreased dorsal raphe nucleus (DRN), increased hippocampus unchanged other...
Background— The mechanism of pulmonary artery smooth muscle cell (PA-SMC) hyperplasia in idiopathic hypertension (iPH) may involve both an inherent characteristic PA-SMCs and abnormal control by external stimuli. We investigated the role microvascular endothelial cells (P-ECs) controlling PA-SMC growth. Methods Results— Serum-free medium quiescent P-ECs elicited marked proliferation, this effect was greater with from patients iPH than subjects these subjects. Fluoxetine, which inhibits...
Deficiency in the monoamine degradation enzyme oxidase A (MAOA) or prenatal exposure to uptake inhibitor cocaine alters behavior humans and rodents, but mechanisms are unclear. In MAOA knock-out mice, inhibiting serotonin synthesis during development can prevent abnormal segregation of axons retinogeniculate somatosensory thalamocortical systems. To investigate this effect, we crossed knock-outs with mice lacking transporter 5-HTT 5-HT1B receptor, two molecules present developing sensory...
One intrinsic abnormality of pulmonary artery smooth muscle cells (PA-SMCs) in human idiopathic hypertension (iPH) is an exaggerated proliferative response to internalized serotonin (5-HT) caused by increased expression the 5-HT transporter (5-HTT). To investigate whether 5-HTT overexpression PA-SMCs sufficient produce PH, we generated transgenic mice overexpressing under control SM22 promoter. Studies SM22-LacZ(+) showed that transgene was expressed predominantly SMCs and systemic vessels....
The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is accounted for by the absence early diagnostic markers and effective treatments. MicroRNAs inhibit translation their target mRNAs. production microRNAs strongly altered in cancers, but causes these alterations are only partially known. DNA hypermethylation a major cause gene inactivation cancer. Our aims were to identify whose expression inactivated PDAC determine whether this hypermethylation-mediated repression an event during...
This phase 1 trial was aimed to determine the safety, pharmacokinetics, and preliminary clinical activity of CYL-02, a nonviral gene therapy product that sensitizes pancreatic cancer cells chemotherapy. CYL-02 administrated using endoscopic ultrasound in 22 patients with concomitantly received chemotherapy (gemcitabine). The maximum-tolerated dose (MTD) exceeded maximal feasible not identified. Treatment-related toxicities were mild, without serious adverse events. Pharmacokinetic analysis...
Although l -dopa remains the most effective treatment of Parkinson disease, its long-term administration is hampered by appearance dyskinesia. Hypersensitivity dopamine D 1 receptors in striatum has been suggested to contribute genesis these delayed adverse effects. However, receptor amounts are unchanged suggesting alterations downstream effectors. In rodents, striatal activate adenylyl cyclase through olfactory type G-protein α subunit (Gαolf) and γ 7 (Gγ7). We found that Gαolf was...
Background— Serotonin (5-hydroxytryptamine; 5-HT) overproduction is responsible for cardiac valvular disease in patients with carcinoid tumors. Reduced 5-HT inactivation one proposed mechanism of the valvulopathy observed individuals treated appetite suppressants fenfluramine and phentermine. One key protein limiting systemic availability transporter (5-HTT) expressed by platelets pulmonary vascular cells; 5-HTT uptake subsequent amine passing through lung. Here we investigated whether...
Numerous data showed that 5-hydroxytryptamine-1A (5-HT1A) receptors couple to Galpha(o)/alpha(i) proteins for signal transduction. However, the alpha subunit isoforms really involved in 5-HT1A receptor coupling brain remain be identified. Moreover, regional differences functional characteristics of have been evidenced repeatedly. Because such could due variations G interacting with same receptor, relevant approaches were used identifying subunits physically coupled different regions rat...
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. Despite significant progresses in last decades, origin this cancer remains unclear and no efficient therapy exists. PDAC does not arise de novo: three remarkable different types pancreatic lesions can evolve towards cancer. These precursor include: intraepithelial neoplasia (PanIN) that are microscopic pancreas, Intraductal Papillary Mucinous Neoplasms (IPMN) Cystic (MCN) both macroscopic lesions. However,...
Abstract Cytidine deaminase (CDA) functions in the pyrimidine salvage pathway for DNA and RNA syntheses has been shown to protect cancer cells from deoxycytidine-based chemotherapies. In this study, we observed that CDA was overexpressed pancreatic adenocarcinoma patients at baseline essential experimental tumor growth. Mechanistic investigations revealed localized replication forks where it increased speed, improved fork restart efficiency, reduced endogenous stress, minimized breaks,...
Mice (GR-i) bearing a transgene encoding glucocorticoid receptor (GR) antisense RNA under the control of neuron-specific neurofilament promoter were used to investigate effects 4 week chronic mild stress (CMS) on hypothalamo–pituitary–adrenocortical (HPA) axis and serotoninergic system in transgenic model vulnerability affective disorders. GR-i mice showed decrease both GR-specific binding (hippocampus cerebral cortex) GR mRNA levels [hippocampus, cortex, dorsal raphe nucleus (DRN)] as well...
ELECTROPHYSIOLOGICAL and biochemical approaches were used to assess possible changes in central 5-HT neurotransmission mice that had been subjected chronic ultramild stress for 8 weeks. This treatment produced a significant decrease the potency of 5-HT1A agonist ipsapirone inhibit electrical activity serotoninergic neurons dorsal raphe nucleus, without modifying receptor binding various brain areas. These data demonstrate triggers long term durable functional desensitization somatodendritic...
The consequences of the absence 5-HT reuptake on functional properties 5-HT(1A) receptors were examined in dorsal raphe nucleus and hippocampus knock-out mice lacking serotonin transporter (5-HTT). Extracellular recordings showed that application selective inhibitors such as paroxetine citalopram onto brainstem slices resulted a concentration-dependent inhibition neuron firing wild-type 5-HTT+/+ mice, but not 5-HTT-/- mutants. By contrast, receptor agonists ipsapirone 5-carboxamidotryptamine...
Kruppel-like factor (KLF) family members share a three C2H2 zinc finger DNA binding domain, and are involved in cell proliferation differentiation control normal as pathological situations. Studies over the past several years support significant role for this of transcription factors carcinogenesis. KLFs can both activate repress genes that participate cell-cycle regulation. Among them, many up-regulated inhibitors proliferation, whereas promote repressed. However, studies do present...
Mutation of the KRAS oncogene is present in 75% to 95% pancreatic cancer tissues. This study aimed evaluate whether endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), combined with analysis mutation, improves diagnosis cases inconclusive or doubtful cytopathologic analysis.We prospectively included 186 patients a mass (103 men; mean age: 62 y). Cytopathology and mutations, using TaqMan MGB allelic discrimination, were performed on EUS-FNA material. A final was obtained from...
Genetic deficiency of monoamine oxidase-A (MAO-A) induces major alterations mood and behaviour in human. Because serotonin (5-HT) is involved regulation, MAO-A responsible for the catabolism 5-HT, we investigated 5-HT mechanisms knock-out mice (2-month-old) lacking MAO-A, using microdialysis, electrophysiological, autoradiographic molecular biology approaches. Compared to paired wild-type mice, basal extracellular levels were increased ventral hippocampus (+202%), frontal cortex (+96%)...
Developments of technologies for delivery foreign genes to the central nervous system are opening field promising treatments human neurodegenerative diseases. Gene vectors need fulfill several criteria efficacy and safety before being applied humans. The ability drive expression a therapeutic gene in an adequate number cells, maintain long-term expression, allow exogenous control over transgene product essential requirements clinical application. We describe use adenovirus vector encoding...
Serotonin [5-hydroxytryptamine (5-HT)] biosynthesis depends on two rate-limiting tryptophan hydroxylases (Tph): Tph1, which is expressed in peripheral organs, and Tph2, neurons. Because 5-HT involved pulmonary hypertension (PH), we investigated whether genetic variations Tph1 and/or Tph2 affected PH development mice. To examine the functional impact of deficiency hypoxic PH, used Tph1(-/-) mice characterized by very low synthesis rates contents gut lung increased forebrain. With chronic...