Papers by Jean-luc Dreyer
Behavioural Brain Research
Progress in Neuro-Psychopharmacology and Biological Psychiatry
Electron Transport and Oxygen Utilization, 1982
Journal of Receptors and Signal Transduction, 1991
The effects of pyridine nucleotides on the Mg-dependent ATP-stimulated Ca2+ pump and on the ATP-i... more The effects of pyridine nucleotides on the Mg-dependent ATP-stimulated Ca2+ pump and on the ATP-independent Na(+)-Ca2+ exchanger were investigated in rat brain synaptic plasma membranes. Both Ca2+ efflux mechanisms are inhibited by pyridine nucleotides, in the order NADPH greater than NADP greater than NADH greater than NAD with IC50 = ca. 3-4 mM for NADP or NADPH and ca. 5 mM for the other pyridine nucleotides in the case of the ATP-driven Ca(2+)-pump, and with IC50 = 8 to 10 mM for the Na(+)-Ca2+ exchanger. Oxidizing agents such as DCIP or FeCN also affect the Ca(2+)-efflux mechanisms. DCIP and FeCN inhibit the ATP-driven Ca2+ pump but not the Na(+)-Ca2+ exchanger. Inhibition of the ATP-dependent Ca2+ pump is optimal when both a reduced pyridine nucleotide and an oxidizing agent (e.g. DCIP or FeCN) were added together. Under similar experimental conditions the pyridine nucleotide-mediated inhibition of the Na(+)-Ca2+ exchanger is partially removed. Therefore Ca(2+)-efflux mechanisms appear to be controlled in part through the redox environment, probably by means of transplasma membrane dehydrogenases.
Journal of Bioenergetics and Biomembranes, 1990
Plasma membrane redox enzymes have been investigated in synaptic membranes from rat brain nerve t... more Plasma membrane redox enzymes have been investigated in synaptic membranes from rat brain nerve terminals. UV-Vis spectra of intact synaptic plasma membranes are presented and the presence of a b-type cytochrome, detectable at 77°K and sensitive to NADH or NADPH, is shown. The molecular characterization of rat synaptic NADH-dehydrogenases was further performed on solubilized enzymes using a recently developed nondissociating polyacrylamide gel electrophoresis technique. Synaptic plasma membranes were solubilized with 1% sodium cholate or Triton X-114 and centrifuged. The supernatant retained over 60% of the NADH-dehydrogenase activity, tested with either DCIP 2 or ferricyanide as substrates, together with NADH. Both enzyme activities were insensitive toward rotenone. This extraction procedure also solubilized about 50% of the proteins. When submitted to polyacrylamide gel electrophoresis under nondenaturing conditions and stained for NADHdehydrogenase activity, five bands of different mobilities were detected. The multiple NADH-dehydrogenases of synaptic plasma membranes were investigated by means of band excision and the five excised bands each submitted to amino acid analysis and to 2-D electrophoresis. The subunit composition of each band was then deduced, together with the molecular weight and pl of each respective subunit. NADH-dehydrogenases have also been purified by means of FPLC on Mono-P (chromatofocusing) followed by gel filtration on Superose 12. NADH-Dehydrogenase IV and V could be purified in their active forms by this approach.
Biochimica et Biophysica Acta (BBA) - Bioenergetics, 1994
Plasma membranes from most mammalian cells display significant transplasma membrane oxidoreductas... more Plasma membranes from most mammalian cells display significant transplasma membrane oxidoreductase (PMO) activity. The enzymes use an extracellular, impermeant electron acceptor as substrate and intracellular reduced pyridine nucleotide as electron donor. The plasma membrane from a neuroblastoma cell line, NB41A3, has been biotinylated and purified by immunoprecipitation with avidin and antiavidin-antibodies. The protein recovery of an immunopurified membrane preparation was < 0.15% of the protein content in the cell extract. The preparation displays an increase in the specific activity of PMO's of 15-to 20-fold compared to the activity in whole cells. With this approach the presence of a NADH-diaphorase within the cell plasma membrane can be demonstrated. This activity accounts for about one third of the total cellular diaphorase activity. The PMO activity cannot be attributed to an increased permeabilization of the plasma membrane induced upon biotinylation nor to intracellular activity from lysed cells. Activation of basal metabolism (glycolysis) stimulates PMO activity up to approx. 54%, presumably through a raise of the intracellular NADH store. PMO also promotes cell growth at low substrate concentrations (0.1-1 p.M). Native gel electrophoresis of iminobiotinylated and affinity purified plasma membrane extracts displays two diaphorase-positive bands, indicating that a homogeneous cell population may express several PMO activities at the plasma membrane.
European Neuropsychopharmacology, 2020
Recent studies have shown that Lethal-7 (let-7) microRNA (miRNA) is involved in a wide range of p... more Recent studies have shown that Lethal-7 (let-7) microRNA (miRNA) is involved in a wide range of psychiatric disorders such as anxiety, depression, schizophrenia, and cocaine addiction. However, the exact role of let-7d miRNA in regulating ethanol intake and preference remains to be elucidated. The aim of the present study was to clarify the role of accumbal let-7d in controlling ethanol-related behaviors in adult rats. For this purpose, stereotaxic injections of let-7d-overexpressing lentiviral vectors (LV) were administered bilaterally into the nucleus accumbens (Nacc) of Wistar rats. The ethanol-related behaviors were investigated using the twobottle choice (TBC) access paradigm, in which the rats had access to 2.5, 5, and 10% ethanol solutions, the grid hanging test (GHT) and ethanol-induced loss-of-righting-reflex (LORR) test. The results showed that intra-accumbally administered let-7d-overexpressing LV significantly decreased ethanol intake and preference without having significant effects on body weight, consumption or preference for tastants (saccharin and quinine) or ethanol metabolism. Furthermore, accumbal let-7d increased resistance to ethanol-induced sedation in the GHT and LORR test. Most importantly, the data showed that the dopamine D3 receptor (D3R) was a can
Psychopharmacology, 2019
Rationale During the last few decades, alcohol use disorders (AUD) have reached an epidemic preva... more Rationale During the last few decades, alcohol use disorders (AUD) have reached an epidemic prevalence, yet social influences on alcoholism have not been fully addressed. Several factors can modulate alcohol intake. On one hand, stress can reinforce ethanol-induced behaviors and be an important component in AUD and alcoholism. On the other hand, environmental enrichment (EE) has a neuroprotective role and prevents the development of excessive ethanol intake in rodents. However, studies showing the role of EE in chronic psychosocial stress-impaired ethanol-conditioned rewards are nonexistent. Aim The purpose of the current study is to explore the potential protective role of EE on extinction and reinstatement of ethanolconditioned place preference (EtOH-CPP) following chronic psychosocial stress. Methods In the first experiment and after the EtOH-CPP test, the mice were subjected to 15 days of chronic stress, then housed in a standard (SE) or enriched environment (EE) while EtOH-CPP extinction was achieved by repeated exposure to the CPP chambers without ethanol injection. In the second experiment and after the EtOH-CPP test, extinction was achieved as described above. Mice were then exposed to chronic stress for 2 weeks before being housed in a SE or EE. EtOH-CPP reinstatement was induced by a single exposure to the conditioning chambers. Results As expected, stress exposure increased anxiety-like behavior and reduced weight gain. More importantly, we found that EE significantly shortened chronic stress-delayed extinction and decreased the reinstatement of EtOH-CPP. Conclusion These results support the hypothesis that EE reduces the impact of alcohol-associated environmental stimuli, and hence it may be a general intervention for reducing cue-elicited craving and relapse in humans.
European Neuropsychopharmacology, 2018
Supplementary Methods Construction, production of the lentiviral vectors and stereotaxic injectio... more Supplementary Methods Construction, production of the lentiviral vectors and stereotaxic injection The let-7d overexpression was achieved by cloning an approximately 450 bp fragment containing the rat let-7d precursor hairpin loop flanked by BamHI and XhoI restriction sites into pTK431 transfer vector (generous gift from Dr. Tal Kafri, Gene Therapy Center,
Behavioural Brain Research, 2019
International Journal of Neuropsychopharmacology, 2010
Dysfunction of brain dopamine transporter (DAT) has been associated with sensation seeking and im... more Dysfunction of brain dopamine transporter (DAT) has been associated with sensation seeking and impulse-control disorders. We recently generated a new animal model by stereotaxical inoculation of lentiviral vectors, which allowed localized intra-accumbal delivery of modulators for DAT gene : GFP (green fluorescent protein) control, silencers (Sil), a regulatable enhancer (DAT+), or both (DAT+Sil). Wistar male rats were followed both for socio-emotional profiles and for propensity to seek risky, uncertain rewards. Elevated anxiety and affiliation towards an unfamiliar partner emerged in Sil rats. Interestingly, in DAT+Sil rats (and Sil rats to a lesser extent) levels of playful social interaction were markedly reduced compared to controls. These DAT+Sil rats displayed a marked 'gambling-like' profile (i.e. preference for a large/uncertain over a small/sure reward), which disappeared upon doxycyclineinduced switch-off onto DAT enhancer, but consistently reappeared with doxycycline removal. MRIguided 1 H-MRS (at 4.7 T) examinations in vivo (under anaesthesia) revealed changes in the bioenergetic metabolites (phosphocreatine and total creatine) for DAT+Sil rats, indicating a functional up-regulation of dorsal striatum (Str) and conversely a down-regulation of ventral striatum (i.e. nucleus accumbens, NAc). A combined profile of (1) enhanced proneness to gambling and (2) strong social withdrawal is thus associated with altered DAT-induced balance within forebrain dopamine systems. In fact, risk of developing a gambling-prone, social-avoidant psychopathology might be associated with (1) dominant semiautomatic strategies and/or habits, developed within Str circuits, and (2) reduced NAc function, with poorer feedback adjustment on decisions by aversive experiences.
Journal of Cell Science, 2000
Recent evidence has shown a role for the heat shock cognate protein Hsc70 in the response to oxid... more Recent evidence has shown a role for the heat shock cognate protein Hsc70 in the response to oxidative stress. We have investigated the subcellular distribution of Hsc70 by means of laser scanning confocal microscopy in neuroblastoma NB41A3 cells, in fibroblasts R6 cells and in R6-Bcl-2, an apoptosis-resistant cell line, and its function in oxidative stress and in apoptosis has been evaluated. Endogenous Hsc70 is localised predominantly in the cytoplasm in unstressed cells, whereas oxidative stress but not apoptosis induces its translocation into the nucleus. In transfected cells overexpressing Hsc70 increased nuclear translocation and aggregation of Hsc70 in intracellular speckles is observed after oxidative stress and, to a lesser degree, after exposure to apoptotic agents. Bcl-2 did not influence the movement of Hsc70 nor the formation of Hsc70-containing speckles. Nuclear translocation of Hsc70 can be modulated by the expression of components from a previously described plasma m...
Journal of cell science, 2001
Recent studies indicating a role of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in apoptosis... more Recent studies indicating a role of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in apoptosis or oxidative stress has been reported. Using confocal laser-scanning microscopy, we have investigated the cellular distribution of GAPDH in central nervous system (CNS)-derived cells (neuroblastoma mNB41A3), in non-CNS derived cells (R6 fibroblast) and in an apoptosis-resistant Bcl2 overexpressing cell line (R6-Bcl2). Induction of apoptosis by staurosporine or MG132 and oxidative stress by H(2)O(2) or FeCN enhanced the nuclear translocation of endogenous GAPDH in all cell types, as detected by immunocytochemistry. In apoptotic cells, GAPDH expression is three times higher than in non-apoptotic cells. Consistent with a role for GAPDH in apoptosis, overexpression of a GAPDH-green fluorescent protein (GAPDH-GFP) hybrid increased nuclear import of GAPDH-GFP into transfected cells and the number of apoptotic cells, and made them more sensitive to agents that induce apoptosis. Bcl2 overexpres...
Psychopharmacology
. Histological representation of injection placements in the dentate gyrus. The distance anterior... more . Histological representation of injection placements in the dentate gyrus. The distance anterior to bregma (in millimeters) is indicated.
Biochemical Journal
NADH-dichlorophenol-indophenol oxidoreductases (PMOs) were purified from synaptic plasma membrane... more NADH-dichlorophenol-indophenol oxidoreductases (PMOs) were purified from synaptic plasma membranes or synaptic vesicles (small recycling vesicles) from both bovine and rat brains and from a neuroblastoma cell line, NB41A3. Several isoforms could be identified in purified plasma membranes and vesicles. Purification of the enzyme activity involved protein extraction with detergents, (NH4)2SO4 precipitation, chromatography under stringent conditions and native PAGE. PMO activity could be attributed to a very tight complex of several proteins that could not be separated except by SDS/PAGE. SDS/PAGE resolved the purified complex into at least five proteins, which could be micro-sequenced and identified unambiguously as hsc70, TOAD64 and glyceraldehyde-3-phosphate dehydrogenase tightly associated with the brain-specific proteins aldolase C and enolase-gamma. Enzyme activity could be purified from both synaptic plasma membranes and recycling vesicles, yields being much greater from the lat...
Biochemical Journal, 1997
NADH–dichlorophenol-indophenol oxidoreductases (PMOs) were purified from synaptic plasma membrane... more NADH–dichlorophenol-indophenol oxidoreductases (PMOs) were purified from synaptic plasma membranes or synaptic vesicles (small recycling vesicles) from both bovine and rat brains and from a neuroblastoma cell line, NB41A3. Several isoforms could be identified in purified plasma membranes and vesicles. Purification of the enzyme activity involved protein extraction with detergents, (NH4)2SO4 precipitation, chromatography under stringent conditions and native PAGE. PMO activity could be attributed to a very tight complex of several proteins that could not be separated except by SDS/PAGE. SDS/PAGE resolved the purified complex into at least five proteins, which could be micro-sequenced and identified unambiguously as hsc70, TOAD64 and glyceraldehyde-3-phosphate dehydrogenase tightly associated with the brain-specific proteins aldolase C and enolase-γ. Enzyme activity could be purified from both synaptic plasma membranes and recycling vesicles, yields being much greater from the latter ...
European Journal of Biochemistry, 1985
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Papers by Jean-luc Dreyer