Biomedical subjects

Chantal Joubert

Publications and source records attributed to Chantal Joubert.

6 recordsLinked to original sources

PubMed2006

Mouse lines selected for difference in sensitivity to beta-CCM also differ in memory processes.

Methyl-beta-carboline-3-carboxylate (or beta-CCM) is a benzodiazepine receptor ligand with inverse agonist properties. Two strains of mice were selected, one for sensitivity (BS) and one for resistance (BR) to a convulsive dose of beta-CCM. These two strains were then shown to differ in several biochemical, pharmacological and behavioral characteristics; specifically BS mice were less anxious than BR mice. The present work provides evidence of differences in the learning abilities of the two strains. Three different learning tasks were used: spatial delayed discrimination on the 4-hole board, a learned choice between a lit and a dark compartment in a T-maze, and place-learning in an 8-arm radial maze. In all three tasks, BS mice had consistently better performance levels than BR mice.

Animals↗

PubMed2004

Neurochemical and behavioral alterations in glucocorticoid receptor-impaired transgenic mice after chronic mild stress.

Mice (GR-i) bearing a transgene encoding a glucocorticoid receptor (GR) antisense RNA under the control of a neuron-specific neurofilament promoter were used to investigate the effects of a 4 week chronic mild stress (CMS) on the hypothalamo-pituitary-adrenocortical (HPA) axis and the serotoninergic system in a transgenic model of vulnerability to affective disorders. GR-i mice showed a decrease in both GR-specific binding (hippocampus and cerebral cortex) and GR mRNA levels [hippocampus, cerebral cortex, and dorsal raphe nucleus (DRN)] as well as a deficit in HPA axis feedback control (dexamethasone test) compared with paired wild-type (WT) mice. In the latter animals, CMS exposure caused a significant decrease in both GR mRNA levels and the density of cytosolic GR binding sites in the hippocampus, whereas, in the DRN, GR mRNA levels tended to increase. In contrast, in stressed GR-i mice, both GR mRNA levels and the density of GR binding sites were significantly increased in the hippocampus, cerebral cortex, and DRN. Electrophysiological recordings in brainstem slices and [gamma-35S]GTP-S binding measurements to assess 5-HT1A receptor functioning showed that CMS exposure produced a desensitization of DRN 5-HT1A autoreceptors in WT, but not in GR-i, mice. In addition, CMS was found to facilitate choice behavior of WT, but not GR-i, mice in a decision-making task derived from an alternation paradigm. These results demonstrate that impaired GR functioning affects normal adaptive responses of the HPA axis and 5-HT system to CMS and alters stress-related consequences on decision-making behaviors.

Animals↗

PubMed2003

Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse.

Mutations of the parkin gene are the most frequent cause of early onset autosomal recessive parkinsonism (EO-AR). Here we show that inactivation of the parkin gene in mice results in motor and cognitive deficits, inhibition of amphetamine-induced dopamine release and inhibition of glutamate neurotransmission. The levels of dopamine are increased in the limbic brain areas of parkin mutant mice and there is a shift towards increased metabolism of dopamine by MAO. Although there was no evidence for a reduction of nigrostriatal dopamine neurons in the parkin mutant mice, the level of dopamine transporter protein was reduced in these animals, suggesting a decreased density of dopamine terminals, or adaptative changes in the nigrostriatal dopamine system. GSH levels were increased in the striatum and fetal mesencephalic neurons from parkin mutant mice, suggesting that a compensatory mechanism may protect dopamine neurons from neuronal death. These parkin mutant mice provide a valuable tool to better understand the preclinical deficits observed in patients with PD and to characterize the mechanisms leading to the degeneration of dopamine neurons that could provide new strategies for neuroprotection.

Alleles↗

PubMed2003

Posture and balance responses to a sensory challenge are related to anxiety in mice.

Anxiety disorders and balance disorders share common clinical features related to perception such as spatial disorientation or dizziness. The search for the mechanism underlying this core of symptoms led us to investigate impairments in multisensory integration. In mice, the 'rotating beam test' allows analysis of changes in balance control and posture in response to a multisensory challenge. We used the BALB/c and C57BL/6 inbred strains of mice, known for their contrasted anxiety-related behavior. The level of anxiety was also manipulated using anxiolytic and anxiogenic pharmacological compounds. Despite equal sensori-motor abilities, anxious mice were more prone to fall off the rotating beam and showed more imbalance than non-anxious mice. Striking inter-strain differences in posture were also observed. Diazepam and beta-CCM reversed these strain-specific responses in opposite directions. We demonstrated that balance and postural strategies developed in response to a multisensory challenge vary as a function of the level of anxiety in mice.

Animals↗

PubMed2003

Behavioral changes are not directly related to striatal monoamine levels, number of nigral neurons, or dose of parkinsonian toxin MPTP in mice.

Behavioral analyses of mice intoxicated by the parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) have generated conflicting results. We therefore analyzed the relationship between behavioral changes, loss of monoamine levels, and loss of dopaminergic cell bodies in groups of mice intoxicated with acute or subchronic MPTP protocols. Despite a higher degree of neuronal loss in the mice intoxicated using subchronic protocols, dopamine loss was severe and homogeneous in the striatum in all groups. Dopamine levels were less severely reduced in the frontal cortex in the three groups of MPTP-intoxicated mice. Norepinephrine and serotonin levels in the striatum were decreased only in the mice intoxicated with the acute protocol. The most surprising result was that the mice intoxicated with the subchronic protocols were more active than the saline-treated mice. As reported in rats with dopamine depletion in the prefrontal cortex, the hyperactivity observed in our mice could be due to the reduced dopamine levels detected in this structure.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2002

Role of TNF-alpha receptors in mice intoxicated with the parkinsonian toxin MPTP.

The loss of dopaminergic neurons in Parkinson's disease is associated with a glial reaction and the overproduction of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha). TNF-alpha acts via two different receptors, TNFR1 and TNFR2, and is believed to have both a neuroprotective and a deleterious role for neurons. In order to analyze the putative role of TNF-alpha in parkinsonism, we compared the effect of the parkinsonian drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice lacking TNFR1, TNFR2, or both receptors and in wild-type littermates. We show that MPTP does not affect spontaneous activity or anxiety in any of the groups and that it reduces motor activity on a rotarod in double knock out mice but not in mice lacking only one receptor. Postmortem analysis revealed no differences in the number of nigral dopaminergic neurons whatever the group. In contrast, striatal dopamine level was slightly decreased in double knock-out mice and more reduced by MPTP in this group than in the other groups of mice. In addition, dopamine turnover was significantly more increased in double knock out mice after MPTP injection. These data suggest that TNF-alpha does not participate in the death of dopaminergic neurons in parkinsonism but that it slightly alters dopamine metabolism or the survival of dopaminergic terminals by a mechanism involving both receptors.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗