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Jean-Charles Bizot

Jean-Charles Bizot

PhD

About

64
Publications
7,108
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2,472
Citations
Additional affiliations
January 2011 - present
French National Centre for Scientific Research
Position
  • Centre national de la recherche scientifique
January 2005 - present
Université de Nice - Sophia Antipolis

Publications

Publications (64)
Article
Full-text available
Fragile X Syndrome (FXS), the most common inherited form of human intellectual disability (ID) associated with autistic-like behaviors, is characterized by dys-sensitivity to sensory stimuli, especially vision. In the absence of Fragile Mental Retardation Protein (FMRP), both retinal and cerebral structures of the visual pathway are impaired, sugge...
Poster
Full-text available
The intake of a drug of abuse may result from two phenomena: the search of pleasure induced by the drug and the need to relieve withdrawal symptoms of this drug. The potency of mazindol, a potential treatment for ADHD, to reduce heroin addiction was examined by using two tests which account for these two phenomena, which are the main components of...
Article
Full-text available
Fragile X Syndrome (FXS) is caused by a deficiency in Fragile X Mental Retardation Protein (FMRP) leading to global sensorial abnormalities, among which visual defects represent a critical part. These visual defects are associated with cerebral neuron immaturity especially in the primary visual cortex. However, we recently demonstrated that retinas...
Poster
Full-text available
Introduction and Objectives: The enhanced response to a stimulus after repeated exposure is termed sensitization. Most of addictive drugs are known to induce behavioral sensitization (e.g. locomotor activity) and cross sensitization with other drugs of abuse 1,2,3. The aim of the present study was to examine whether repeated administrations of (R,...
Article
Full-text available
Alcohol-dependence is a chronic disease with a dramatic and expensive social impact. Previous studies have indicated that the blockade of two monoaminergic receptors, α1b-adrenergic and 5-HT2A, could inhibit the development of behavioral sensitization to drugs of abuse, a hallmark of drug-seeking and drug-taking behaviors in rodents. Here, in order...
Article
Full-text available
Cognitive impairment in Down syndrome (DS) has been linked to increased synaptic inhibition. The underlying mechanisms remain unknown, but memory deficits are rescued in DS mouse models by drugs targeting GABA receptors. Similarly, administration of epigallocatechin gallate (EGCG)-containing extracts rescues cognitive phenotypes in Ts65Dn mice, pot...
Article
The validity of spontaneous hypertensive rat (SHR) as a model of attention deficit hyperactivity disorder (ADHD) has been explored by comparing SHR with Wistar rats in a test of attention, the two-choice visual discrimination task (2-CVDT). Animals were 4-5 weeks old during the training phase of the experiment and 6-7 weeks old during the testing p...
Article
Full-text available
The trisomy of human chromosome 21 (Hsa21), which causes Down syndrome (DS), is the most common viable human aneuploidy. In contrast to trisomy, the complete monosomy (M21) of Hsa21 is lethal, and only partial monosomy or mosaic monosomy of Hsa21 is seen. Both conditions lead to variable physiological abnormalities with constant intellectual disabi...
Article
Full-text available
Sarizotan 1-[(2R)-3,4-dihydro-2H-chromen-2-yl]-N-[[5-(4-fluorophenyl) pyridin-3-yl]methyl] methenamine, showed an in vivo pharmaco-EEG profile resembling that of methylphenidate which is used in attention deficit/hyperactivity disorder (ADHD). In turn, we tested sarizotan against impulsivity in juvenile rats measuring the choice for large delayed v...
Article
Full-text available
The trisomy of human chromosome 21 (Hsa21), which causes Down syndrome (DS), is the most common viable human aneuploidy. In contrast to trisomy, the complete monosomy (M21) of Hsa21 is lethal, and only partial monosomy or mosaic monosomy of Hsa21 is seen. Both conditions lead to variable physiological abnormalities with constant intellectual disabi...
Article
Trisomy for human chromosome 21 results in Down syndrome (DS), which is among the most complex genetic perturbations leading to intellectual disability. Accumulating data suggest that overexpression of the dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A), is a critical pathogenic mechanisms in the intellectual deficit. Her...
Article
Full-text available
Myotonic dystrophy type 1 is a complex multisystemic inherited disorder, which displays multiple debilitating neurological manifestations. Despite recent progress in the understanding of the molecular pathogenesis of myotonic dystrophy type 1 in skeletal muscle and heart, the pathways affected in the central nervous system are largely unknown. To a...
Article
Full-text available
Vezatin is an integral membrane protein associated with cell-cell adhesion complex and actin cytoskeleton. It is expressed in the developing and mature mammalian brain, but its neuronal function is unknown. Here, we show that Vezatin localizes in spines in mature mouse hippocampal neurons and codistributes with PSD95, a major scaffolding protein of...
Article
Full-text available
Vesicular (v)- and target (t)-SNARE proteins assemble in SNARE complex to mediate membrane fusion. Tetanus neurotoxin-insensitive vesicular-associated membrane protein (TI-VAMP/VAMP7), a vesicular SNARE expressed in several cell types including neurons, was previously shown to play a major role in exocytosis involved in neurite growth in cultured n...
Article
Full-text available
The cystathionine β-synthase (CBS) gene, located on human chromosome 21q22.3, is a good candidate for playing a role in the Down Syndrome (DS) cognitive profile: it is overexpressed in the brain of individuals with DS, and it encodes a key enzyme of sulfur-containing amino acid (SAA) metabolism, a pathway important for several brain physiological p...
Data
Coomassie blue staining of the SDS-PAGE blotted in (A) fig. 2A and (B) fig. 2B. (TIF)
Data
Limited metabolic profiling of hippocampus. (DOC)
Article
Full-text available
Down syndrome (DS) is a complex genetic syndrome characterized by intellectual disability, dysmorphism and variable additional physiological traits. Current research progress has begun to decipher the neural mechanisms underlying cognitive impairment, leading to new therapeutic perspectives. Pentylenetetrazol (PTZ) has recently been found to have p...
Poster
Full-text available
Results The number of choices for the large-but-delayed reward was increased by mazindol (1-10 mg/kg), modafinil (64 mg/kg) and BLK-032 (64-256 mg/kg) but was not significantly altered by BLK-030 (64, 128 mg/kg) nor by haloperidol (0.01-0.3 mg/kg). Effects of methylphenidate (Mph), d-amphetamine (D-Amphet), modafinil (Modaf) and haloperidol (Halo)...
Article
Impulsivity is a core symptom of Attention Deficit/Hyperactivity Disorder (ADHD). In the present study, we assessed the effects of two stimulants, methylphenidate and d-amphetamine and of two non stimulant noradrenaline reuptake inhibitors, atomoxetine and desipramine, on the tolerance to delay of reward, taken as an index of impulsivity, in juveni...
Article
A novel pyridine derivative, 8-{4-[(6-methoxy-2,3-dihydro-[1,4]dioxino[2,3-b]pyridine-3-ylmethyl)-amino]-butyl}-8-aza-spiro[4.5]decane-7,9-dione hydrochloride, termed JB-788, was designed to selectively target 5-HT1A receptors. In the present study, the pharmacological profile of JB-788 was characterized in vitro using radioligands binding tests an...
Article
Full-text available
Mental retardation in Down syndrome (DS), the most frequent trisomy in humans, varies from moderate to severe. Several studies both in human and based on mouse models identified some regions of human chromosome 21 (Hsa21) as linked to cognitive deficits. However, other intervals such as the telomeric region of Hsa21 may contribute to the DS phenoty...
Article
Full-text available
Individuals with partial HSA21 trisomies and mice with partial MMU16 trisomies containing an extra copy of the DYRK1A gene present various alterations in brain morphogenesis. They present also learning impairments modeling those encountered in Down syndrome. Previous MRI and histological analyses of a transgenic mice generated using a human YAC con...
Article
Engrailed1 is a developmental gene of the homeogene family that controls the survival of midbrain dopaminergic neurons throughout life. Since these neurons have been crucially implicated in Parkinson's disease (PD), transgenic mice lacking one En1 allele could be of particular interest for the development of an animal model for PD. We showed in En1...
Article
Full-text available
Monosomy 21 is a rare human disease due to gene dosage errors disturbing a variety of physiological and morphological systems including brain, skeletal, immune and respiratory functions. Most of the human condition corresponds to partial or mosaic monosomy suggesting that Monosomy 21 may be lethal. In order to search for dosage-sensitive genes invo...
Article
Impulsivity is a core symptom of attention deficit/hyperactivity disorder (ADHD). The spontaneously hypertensive rats (SHR) is a strain commonly used as an animal model of ADHD. However, there is no clear evidence that psychostimulants, which are used for treatment of ADHD, reduce impulsivity in SHR. Because ADHD mainly affects children, it may be...
Article
The aim of this study was to evaluate the effects of various drugs which present antidepressant properties: selective serotonin-reuptake inhibitors (SSRIs, fluoxetine), serotonin and noradrenaline-reuptake inhibitors (Desipramine) and phosphodiesterase inhibitors (PDE, rolipram and tofisopam) on bone microarchitecture and biomechanical properties....
Article
A radionuclide that accumulates in the central nervous system is likely to exert both a chemical and a radiological effect. The present study aimed at assessing the behavioral effect of two radionuclides previously shown to accumulate in the central nervous system after chronic exposure--uranium and cesium. Rats were exposed for 9 months to drinkin...
Article
Full-text available
Engrailed1 and Engrailed2 (En1 and En2) are two developmental genes of the homeogene family expressed in the developing midbrain. En1 and, to a lesser degree, En2 also are expressed in the adult substantia nigra (SN) and ventral tegmental area (VTA), two dopaminergic (DA) nuclei of the ventral midbrain. In an effort to study En1/2 adult functions,...
Article
Full-text available
The sensing of head movement in mammals depends upon the vestibular endorgan of the inner ear, a complex structure made up of the semicircular canals and otoliths. Due to the similarity between the human and mouse vestibular apparatus, the analysis of mutant mouse is a valuable strategy aiming to identify genes involved in the control of balance an...
Article
The effect of apamin on learning was examined using two behavioral tasks where the animals were subjected to two trials separated by a 24h interval. In the Y maze task, apamin administered before the acquisition session did not enhance performance on both the acquisition session and the restitution session. In the second behavioral task, animals we...
Article
The effect of a sulbutiamine chronic treatment on memory was studied in rats with a spatial delayed-non-match-to-sample (DNMTS) task in a radial maze and a two trial object recognition task. After completion of training in the DNMTS task, animals were subjected for 9 weeks to daily injections of either saline or sulbutiamine (12.5 or 25 mg/kg). Sul...
Article
Effects of unpredictable chronic mild stress (UCMS) on anhedonic-like behaviour, physical state, body weight, learning and memory were investigated in three strains of mice. These strains were chosen among 11 strains that were tested in a first experiment for their sucrose consumption and preference for sucrose solutions of different concentrations...
Article
Recent experiments have shown that mice lacking the alpha1b-adrenergic receptor (alpha1b-AR KO) are less responsive to the locomotor hyperactivity induced by psychostimulants, such as D-amphetamine or cocaine, than their wild-type littermates (WT). These findings suggested that psychostimulants induce locomotor hyperactivity not only because they i...
Article
Effects of low to mild doses of soman on central and blood cholinesterase (ChE) activities and anxiety behavior were studied in mice 30 min, 24 h and 7 days after poisoning. At these two latter time points, histopathological consequences of soman intoxication were also studied. The 30-microg/kg dose of soman produced 30 min after intoxication, abou...
Article
Tolerance to delay of gratification, taken to reflect impulsiveness, has been proposed to be under the preferential control of central serotonin (5-HT) processes. The present study further examined the effects of drugs which directly or indirectly alter 5-HT transmission, on behaviour controlled by a delayed positive reinforcer. Rats were given the...
Article
The present study describes the effects of intraseptal infusions of 1 nmol AMPA and 12 nmol NBQX on both frequency and amplitude of physostigmine-induced theta rhythm in urethane-anesthetized rats. Infusion of AMPA increased the theta frequency. This effect was blocked by a prior infusion of NBQX. Infusion of NBQX decreased the theta amplitude, and...
Article
Nicotine was investigated for its mnemonic effect in a two trials object recognition task. In the first trial, two copies of the same object were presented. In the second trial (24 h after), one of the familiar object and a new object were presented. The time spent exploring the new object by control rats was not significantly different from the ex...
Article
The present study describes the effects of intraseptal microinjections of 2 nmol of AP5 upon memory of rats subjected to a two trial object recognition task. This task allows us to detect either a disruption or an improvement of memory according to the duration of the interval between the sample trial (T1) and the choice trial (T2). AP5 injected be...
Article
This study consists of two parts, first to compare the pharmacological profile of atropine and CEB-1957 substance toward muscarinic receptor subtypes. In various rat brain structures, binding properties were determined by competition experiments of [3H]pirenzepine, [3H]AF-DX 384, and [3H]4-DAMP in quantitative autoradiography of M1, M2, and M3 musc...
Article
The neurotoxicity of Penitrem A (PA) in rats was assessed against neurophysiological, behavioral and histopathological parameters. Animals were acutely given intracerebroventricular (22-45 mg) or intraperitoneal injections (0.5-1.5 mg/kg) of PA. A typical trembling syndrome associated with PA was always noted. Depending on the dose administered, an...
Article
The effects of various drugs were assessed in rats responding under a Differential-Reinforcement-of-Low-Rate 30-s (DRL 30-s) schedule. Atropine, scopolamine, and CEB-1957 (a new muscarinic blocker) increased response rate and decreased reinforcement rate, while methylatropine only decreased reinforcement rate. Physostigmine decreased response and r...
Article
The present study describes the effects of intraseptal microinjections of N-methyl-D-aspartate (NMDA) or AP5, an agonist and an antagonist of the NMDA receptors, respectively, upon memory of rats. Animals were injected with the drug or vehicle immediately after the first exposure to two identical objects, and the duration of exploration of the fami...
Article
Male Wistar rats were trained, in two-lever operant chambers, to press one lever (L5) after the presentation of a conditioned stimulus (a light) for 5 s (CS5) or the other lever (L20) after a conditioned stimulus for 20 s (CS20). Various drugs were administered before experimental sessions, during which CS5, CS20 and a stimulus of the intermediate...
Article
The effects of apamin, a selective blocker of the small conductance K(Ca) channels were examined in both passive avoidance and habituation of exploratory activity in rats. In the two experiments, animals were subjected to two trials separated by a 24 h interval. Apamin was administered either before or after the first session (acquisition) or befor...
Article
Object recognition was investigated in rats in a two trial unrewarded task. In the first trial, two copies of the same object were presented. In the second trial, one of the familiar object and a new object were presented. Rats explored the new object longer than the familiar object when the intertrial time was 1 h, indicating that they remembered...
Article
Intraperitoneal administration of the mycotoxin penitrem A 30 min before a training session in passive avoidance task, impaired performance of rats subjected to a test-session 24 h after. This effect was not antagonised by pretraining administration of physostigmine or bicuculline. Administration of penitrem A 20 min before a training session or 30...
Article
Performance in cognitive tasks which require the subject to wait and/or to process a large amount of information can be disrupted by an increase in impulsive-like behaviour. Accordingly, a decrease in impulsive-like behaviour can improve performance in such tasks. Conversely, impulsive-like behaviour may improve performance in cognitive tasks where...
Article
Benzodiazepine (Bzd) agonist, diazepam (Dzp) and inverse agonist methyl beta-carboline-3-carboxylate (beta-CCM); acetylcholinesterase inhibitor, physostigmine (Physo) and muscarinic antagonist, scopolamine (Scopo), were investigated for their mnesic effect in a passive avoidance (PA) task in rats. Impairments were observed after Dzp- and/or Scopo-p...
Article
This study investigated in rats the action of a variety of antidepressants in two behavioral models. In model 1, animals trained in a T-maze were allowed to choose between 2 magnitudes of reward: immediate but small reward (2 pellets) vs. a 25-sec delayed but large reward (10 pellets). Under this alternative, vehicle-injected rats selected the larg...

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