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P Barnéoud

Publications and source records attributed to P Barnéoud.

At least 19 recordsLinked to original sources
PubMed2000

Evaluation of simple and complex sensorimotor behaviours in rats with a partial lesion of the dopaminergic nigrostriatal system.

We have examined the behavioural consequences of a partial unilateral dopaminergic denervation of the rat striatum. This partial lesion was obtained by an intrastriatal 6-hydroxy-dopamine injection (6-OHDA, 20 or 10 microgram divided between two injection sites) and was compared with a unilateral complete lesion resulting from an injection of 6-OHDA (2 x 6 microgram) into the medial forebrain bundle. Quantification of striatal dopamine (DA) and its metabolites, and the immunohistochemical evaluation of the nigrostriatal DA system confirmed the complete and partial lesions. Animals with complete striatal denervation displayed both apomorphine- and amphetamine-induced rotations whereas the partial denervation elicited amphetamine-induced rotations only. However, the rates of amphetamine-induced rotation were not correlated with the size of the lesion. In contrast, the paw-reaching impairments were significantly correlated with the striatal dopaminergic depletion. When evaluated in the staircase test, animals with partial denervation were impaired exclusively for the paw contralateral to the side of the lesion. This motor deficit (50-75%) included all components of the skilled paw use (i.e. attempt, motor coordination and success) and was observed at least 12 weeks after the lesion. However, these animals were able to perform normal stepping adjustments with the impaired paw, indicating that the partial lesion induced a coordination deficit of the paw rather than a deficit of movement initiation. After a complete lesion, stepping adjustments of the contralateral paw were dramatically impaired (by 80%), an akinesia which almost certainly accounted for the great deficit in skilled paw use. The paw-reaching impairments resulting from the partial striatal denervation are proposed as a model of the early symptoms of Parkinson's disease and may be useful for the development of restorative therapies.

Amphetamine↗
PubMed1999

Protection of axotomized ganglion cells by salicylic acid.

Neuronal survival is influenced by the redox environment, and it has been shown that antioxidants protect developing neurons from the effects of axotomy. Here, we show that the intraocular injection of salicylic acid (SA) reduces the number of dying axotomized ganglion cells in the chick embryo. The antioxidant properties of SA are probably responsible for its protective effects, whose U-shaped dose-dependency matches that of several other antioxidants. We conclude that SA protects axotomized neurons by maintaining the redox status near an optimal set-point.

Animals↗
PubMed1999

Effects of mild traumatic brain injury on immunoreactivity for the inducible transcription factors c-Fos, c-Jun, JunB, and Krox-24 in cerebral regions associated with conditioned fear responding.

We have previously demonstrated that mild traumatic brain injury (TBI) of the right parietal cortex results in a relatively selective deficit in conditioned fear responding. However, this behavioural deficit is very consistent and unrelated to the extent of the cortical necrotic lesion. We were therefore interested in determining if other brain regions might show a consistent response to mild TBI, and therefore, more reliably relate to the behavioural change. Increased expression of inducible transcription factors (ITFs) has been used to study which brain regions respond to a variety of events. In the present study, we examined the expression patterns of immunoreactivity (IR) for four ITFs (c-Fos, c-Jun, JunB, and Krox-24) at 3 h after mild fluid percussion TBI. Changes in ITF expression were only observed ipsilateral to the side of TBI. The clearest changes were observed in brain regions known to be involved in conditioned fear responding, such as the amygdala complex and hippocampal formation and several cortical regions. In contrast, no changes in IR for any of the ITFs were observed in the striatum, nucleus accumbens, nucleus basalis magnocellularis, septum or periacqueductal grey. Unlike the extent of visible damage to the cortex at the site of impact, the overexpression of ITFs showed a notable consistency between animals subjected to TBI. This consistency in regions known to be involved in conditioned fear responding (i.e., amygdala complex and hippocampal formation) lead us to suggest that it is these changes, rather than the more variable cortical necrotic lesion, that is responsible for the behavioural deficits we observe following mild TBI. Importantly, our results demonstrate that like the hippocampus, the amygdala is a sub-cortical structure particularly sensitive to the effects of mild brain trauma and underline the fact that cerebral regions distant from the location of the fluid impact can be affected.

Amygdala↗
PubMed1999

Beneficial effects of lysine acetylsalicylate, a soluble salt of aspirin, on motor performance in a transgenic model of amyotrophic lateral sclerosis.

We have studied the effect of lysine acetylsalicylate (LAS; Aspegic), a soluble salt of aspirin, on motor deficits in transgenic mice expressing a human superoxide dismutase SOD1 mutation (Gly-93 --> Ala), an animal model of familial amyotrophic lateral sclerosis (FALS). In nontreated FALS mice, motor impairments appear at 12-14 weeks of age, whereas paralysis is not observed before 20 weeks of age. Life expectancy is 140-170 days. Early treatment with LAS from 5 weeks of age delayed the appearance of motor deficits in FALS mice as measured by extension reflex, loaded grid, and rotarod tests. This beneficial effect of treatment was maintained up to 18 weeks of age, until just before onset of end-stage disease. When treatment was started at 13 weeks, no significant beneficial effect was observed. These results demonstrate that chronic LAS treatment is able to delay the appearance of reflex, coordination, and muscle strength deficits in this animal model of ALS if the treatment is started early enough. However, neither the onset of paralysis nor end-stage disease were improved by the LAS treatment. In the absence of an effect on survival, the functional improvement demonstrated here is probably the maximum that this demanding model could allow. Although other properties of LAS may have contributed to its beneficial effect, we suggest that the antioxidant properties of aspirin are responsible for the positive effects in this model and support the use of antioxidants as effective therapy for ALS.

Amyotrophic Lateral Sclerosis↗
PubMed1998

Nicotinic acetylcholine subunit mRNA expression in dopaminergic neurons of the rat substantia nigra and ventral tegmental area.

The molecular composition of the nicotinic acetylcholine receptors (nAChRs) located on dopaminergic neurons and modulating their activity is unclear. Using the reverse transcriptase-polymerase chain reaction we have analyzed the mRNA for nAChR subunits expressed in the substantia nigra (SN) and ventral tegmental area (VTA) following unilateral 6-hydroxydopamine lesion of the dopaminergic system. In contrast to the unlesioned hemisphere, no signal was found in the lesioned hemisphere for alpha3, alpha5, alpha6 and beta4 subunits in the SN nor for alpha2, alpha3, alpha5, alpha6, alpha7 and beta4 subunits in the VTA, indicating the expression of these subunits in dopaminergic neurons. mRNA for alpha4, beta2 and beta3 subunits (and alpha7 in the SN) were still detected after lesion, suggesting that they are expressed in GABAergic neurons and interneurons of these brain areas. These results demonstrate the selective localisation of a number of nAChR subunit mRNA within dopaminergic neurons, strongly suggesting that a heterogenous population of nAChRs play a role in modulating dopaminergic neuronal activity.

Animals↗
PubMed1998

Neuroprotective effect of eliprodil: attenuation of a conditioned freezing deficit induced by traumatic injury of the right parietal cortex in the rat.

We have previously demonstrated that a lateral fluid percussion-induced traumatic lesion of the right parietal cortex can lead to a deficit in a conditioned freezing response and that this deficit can be attenuated by both pre- and postlesion administration of the NMDA receptor antagonist dizocilpine. In the present study, we investigated the effects of eliprodil, a noncompetitive NMDA receptor antagonist acting at the polyamine modulatory site, which also acts as a Ca2+ channel blocker, on the trauma-induced conditioned freezing deficit. Eliprodil produced a 50% reduction in this deficit when administered as three 1 mg/kg injections i.v. at 15 min, 6 h, and 24 h following the lesion. Approximately the same degree of protection was afforded when 2 x 1.5 mg/kg were administered 6 and 24 h and equally at 12 and 24 h after surgery (56% and 59%, respectively). A single treatment (3 mg/kg) at 24 h was ineffective against the deficit. The protection afforded with treatment at 6 and 24 h after lesion was dose dependent, with a minimal active dose of 2 x 0.75 mg/kg. These data complement those previously published on the ability of eliprodil to reduce lesion volume following traumatic brain injury and show, in addition, that the neuroprotective effect has functional consequences.

Analysis of Variance↗
PubMed1997

Quantitative motor assessment in FALS mice: a longitudinal study.

We have evaluated the G1H line of transgenic mice overexpressing a familial ALS mutation of SOD1 (Gly-93-->Ala) in tasks assessing different aspects of motor function to determine how early these deficits could be detected and their order of appearance. The earliest deficits were observed in tests of muscle strength and coordination as early as 8 weeks of age and their development appeared to be biphasic, whereas spontaneous activity was not impaired until 15 weeks of age. These studies show that, in addition to the previously demonstrated histological and electromyographic deficits, this transgenic mouse also presents changes in motor function reminiscent of the human disease, reinforcing and extending its validity as an animal model of familial amyotrophic lateral sclerosis (FALS) and allowing the investigation of novel drug treatment for ALS.

Amyotrophic Lateral Sclerosis↗
PubMed1996

Neuroprotective effects of riluzole on a model of Parkinson's disease in the rat.

The aim of the present study was to analyse whether riluzole, a compound that interacts with the voltage-dependent sodium channel and impairs glutamatergic transmission, would exhibit a neuroprotective activity in a model of Parkinson's disease in the rat. Impaired skilled forelimb use, circling behavior, and altered dopaminergic metabolism of the mesotelencephalic system were evaluated in unilaterally 6-hydroxydopamine-lesioned rats. Riluzole was administered twice 15 min before, and 24 h after, the lesion. Riluzole reduced both the contralateral rotations induced by apomorphine and the ipsilateral ones elicited by amphetamine. Moreover, the decreased dopaminergic metabolism seen after 6-hydroxydopamine injection was attenuated in the riluzole-treated animals, at both the striatal and nigral levels. These biochemical and behavioral results demonstrate the ability of riluzole partially to protect the degeneration of the nigrostriatal dopaminergic neurons induced by the toxin 6-hydroxydopamine. Perhaps, the most striking evidence for the protective effect of riluzole was that this compound improved the skilled paw use, a complex sensorimotor behavior which is not easily ameliorated by palliative therapies such as dopaminergic grafts. These results extend previous data showing that riluzole counteracts the toxicity induced by 1-methyl-4-1,2,3,6-tetrahydropyridine and 1-methyl-4-phenylpyridinium in rodent dopaminergic neurons. The use of riluzole may be considered of potential interest for the neuroprotective therapy of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1995

Effects of complete and partial lesions of the dopaminergic mesotelencephalic system on skilled forelimb use in the rat.

This study compares certain behavioural consequences of partial and complete unilateral lesions of the dopaminergic mesotelencephalic system. We investigated skilled forelimb use, rotations induced by apomorphine and amphetamine, and dopaminergic metabolism of the nigrostriatal system of rats that had received a unilateral injection of 6-hydroxydopamine into the medial forebrain bundle. The rats classified Apo(+), that rotated after the administration of apomorphine, had a complete lesion of the nigrostriatal system, whereas those classified Apo(-), that did not rotate after the administration of apomorphine, had a partial lesion of the nigrostriatal system. In the Apo(+) rats, 99.8% of the dopamine in the striatum was depleted, as was 85% of that in the substantia nigra. For the Apo(-) rats, 72% of the dopamine in the striatum was depleted as was 56% of that in the substantia nigra. When investigated with the staircase test, the animals with the most severe dopamine depletions were those most impaired in the paw reaching task. Complete and partial unilateral depletions of the dopaminergic mesotelencephalic system impaired the hierarchic phases of paw reaching differently. A complete dopamine depletion, but not a partial one, decreased the number of attempts made with the contralateral paw, and induced a bias towards the ipsilateral paw. A partial dopamine lesion impaired the sensorimotor co-ordination of both paws, whereas the complete dopamine lesion had a greater effect on the contralateral paw than on the ipsilateral paw. The mild paw reaching impairments observed in animals with moderate depletions of dopamine are proposed as a model of the early symptoms of Parkinson's disease that may be useful for the development of protective or restorative therapies.

Animals↗
PubMed1994

Direct intracerebral gene transfer of an adenoviral vector expressing tyrosine hydroxylase in a rat model of Parkinson's disease.

Direct intracerebral gene transfer to neural cells has been demonstrated with recombinant adenovirus encoding beta-galactosidase. To explore the potential of recombinant adenovirus for the therapy of neurological disease we constructed a recombinant adenovirus encoding tyrosine hydroxylase and optimized intracerebral injection to express the gene in the striatum of unilaterally denervated rats. These animals have dopamine depletion in their lesioned striatum, causing a rotation asymmetry induced by apomorphine. One and two weeks after intracerebral injection this sensorimotor asymmetry was decreased by the adenovirus encoding tyrosine hydroxylase and not by a control adenovirus encoding beta-galactosidase. Histological analysis showed that tyrosine hydroxylase was preferentially expressed in astrocytes.

Adenoviridae↗
PubMed1994

Vision influences paw-preference in mice.

We studied the influence of vision on the expression of handedness in mice. In one experiment we submitted adult mice that had an opaque scleral contact lens fitted to one eye, to a paw-preference testing procedure. When the eye was occluded before training, the animals showed a clear preference for the paw ipsilateral to the open eye; however, we could not induce a shift in a previously determined, natural, paw-preference when the lens was placed over the eye ipsilateral to the spontaneously preferred paw; these results indicate that vision plays a role in the animal's choice of a paw during the learning phase of the paw-preference test. In a second experiment adult mice that had been subjected to unilateral eye removal at birth, underwent the same test. The enucleation did not appear to influence handedness with respect to both direction and strength. The latter result--we propose--reflects a reorganization of the visual system induced by neonatal enucleation.

Animals↗
PubMed1993

Direction of handedness linked to hereditary asymmetry of a sensory system.

Studies on the role of heredity in the transmission of handedness in nonhuman mammals have, so far, led to the isolation of mouse strains that differed in the lateralized versus ambidextrous use of the forepaw in a food-retrieval task (strength of paw preference). Here we report that left versus right use of the forepaw (direction of paw preference) is associated with a genetically expressed structural asymmetry of a sensory system, the whisker-to-barrel pathway. Mice that express whisker pad asymmetry of a direction that corresponds with the asymmetry for which they were bred demonstrate an opposite shift in the distribution of handedness: a right or left dominance of the whisker pad predicts a high proportion of left-handers or right-handers, respectively. Is an altered brain circuit--that is, a consequence of the asymmetry of the whisker pad--associated with a change in the circuitry that governs handedness? Or, alternatively, are there two gene sets responsible for the phenomena that we report--one that causes "whiskeredness" and another that causes handedness?

Animals↗
PubMed1991

Vibrissa-related behavior in mice: transient effect of ablation of the barrel cortex.

Knowing that the mystacial vibrissae are an important part of the tactile sensory apparatus of rodents, we investigated the role of the barrel cortex - the endstation of the pathway between whiskerpad and cerebral cortex - in mouse behavior. We tested 15 female adult mice 2 and 10 weeks after both unilateral ablation of the barrel cortex and removal of the vibrissae on the same side in order to assess acute as well as transient effects of the cortical lesion. Two kinds of behavioral tests were performed on animals permanently provided with opaque lenses: one involved a passive stimulation of the vibrissae; the other was the 'gap-crossing' test which required the animal's active use of the vibrissae. Lesioned subjects did not show a deficit during passive stimulation of the vibrissae. On the contrary, there was a deficit during the gap-crossing test 2 weeks after the ablation of the barrel cortex. The deficit partly disappeared when the subjects were tested 10 weeks later. The results show that in mice, the barrel cortex is involved in the performance of complex behavioral tasks. The recovery of function could be due to changes in strategies to solve the gap-crossing test and/or to physical changes in neuronal circuitry. In either case, the results are relevant for the interpretation of cortical transplantation models using the whisker-to-barrel pathway.

Animals↗
PubMed1991

Functional brain asymmetry and lymphocyte proliferation in female mice: effects of right and left cortical ablation.

Brain immunomodulation may be lateralized as evidenced by two experimental approaches. Using a behavioral paradigm, we have reported an association between asymmetrical brain function and lymphocyte reactivity in mice selected for right- and left-paw preference. Left-handed mice, in comparison to right-handers, exhibit higher mitogen-induced T-lymphocyte proliferation. Using a cortical lesion paradigm in mice, it has been previously shown that each hemicortex modulates in opposite directions lymphocyte reactivity. In these experiments, the role of the brain cortex in the association between paw preference and immune reactivity was assessed by studying mitogen-induced lymphoproliferation in left- and right-handed mice after right or left-cortical ablation. The difference in T-lymphocyte responsiveness between right- and left-handed mice persisted after right lesions but was abolished after left lesions. This immunological effect of left cortical ablation is hypothesized to involve the hypothalamic dopaminergic neurons.

Analysis of Variance↗
PubMed1990

Asymmetric distribution of brain monoamines in left- and right-handed mice.

Biogenic amine distributions analyzed in the cerebral neocortex, striatum, anterior hypothalamus, and bulbospinal region, were compared between both hemispheres of left- and right-handed mice. The handedness of mice was determined using a paw preference test. The animals were tested 5 times, once every two weeks, and the biochemical analysis was performed two weeks after the last behavioral evaluation. The results indicated that (1) asymmetrical monoaminergic concentrations exist in the mouse brain. Monoamine contents were found to be higher in the right parietal cortex and anterior hypothalamus than in the left ones; (2) besides the behavioral expression of handedness, left- and right-handed subpopulations of mice differ according to asymmetrical distributions of cortical and bulbospinal NE contents as well as DA turnover of the tuberoinfundibular system.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Functional brain asymmetry and murine systemic lupus erythematosus.

The role of brain lateralization in antibody production was studied in a murine systemic lupus erythematosus model. Male and female New Zealand black mice that spontaneously produce pathogenic auto-antibodies directed against red blood cells and DNA, were divided into right- and left-handers using a paw preference test, and anti-erythrocyte and anti-DNA antibody production was repeatedly determined. In females, antibodies against erythrocytes and double-stranded DNA appeared earlier in left-handers. These results provide the first evidence of an association between a functional brain asymmetry and auto-antibody production and suggest the involvement of the central nervous system in the pathogenesis of autoimmune processes.

Aging↗
PubMed1989

Brain neocortex modulation of mitogen-induced interleukin 2, but not interleukin 1, production.

Interleukin 2 (IL-2) production by splenic T cells stimulated by Concanavalin A was studied in mice after unilateral or bilateral brain neocortex ablation. The brain cortex was shown to modulate IL-2 production in an asymmetrical way. IL-2 levels were higher in animals with a right cortical lesion (group R) and lower in mice with a symmetrical lesion (group L) as compared to controls, differences between groups R and L being significant. Such variations of IL-2 production that were observed after unilateral lesions were abolished with bilateral cortical ablations. These results extend the immunoregulatory roles of the brain neocortex to IL-2 production by splenic T cells and may provide molecular support for neuro-immunological networks.

Animals↗