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C Strazielle

Publications and source records attributed to C Strazielle.

53 records · Page 3Linked to original sources
PubMed2000

Autoradiography of glutamate receptor binding in adult Lurcher mutant mice.

The mutation Lurcher, resulting from a gain of malfunction of the delta2 glutamate receptor expressed specifically by cerebellar Purkinje cells, causes a primary total loss of these neurons of the cerebellar cortex, as well as the secondary degeneration of cerebellar granule and inferior olive neurons. The distributions of glutamate receptors sensitive to amino-methylisoxazole-propionic acid (AMPA), to kainic acid (KA), and to N-methyl-D-aspartic acid (NMDA) as well as metabotropic sites (MET1 and MET2) were examined in wild type and Lurcher mice by quantitative autoradiography. This study was undertaken to determine the gene effect on the distribution of the various glutamate receptor subtypes, as well as how the cerebellar lesion affects the glutamatergic system in other brain regions. In cerebellum, there were postsynaptic AMPA and metabotropic receptors on Purkinje cells, postsynaptic NMDA receptors on granule cells, as well as KA receptors on granule cells or on parallel fibers. Taking into account surface areas, binding to all receptor subtypes was lower in the cerebellar cortex of Lurcher mutants than in wild type mice, while in the deep cerebellar nuclei only KA receptors were diminished. In other brain regions, the alterations followed always the same pattern characterized by a decrease of NMDA and KA receptors but with an increase of AMPA sites; these reciprocal changes were seen in thalamus. neostriatum, limbic regions, and motor cerebral cortical regions. Comparisons of glutamate receptor distribution in Lurcher mutants and in human autosomal cerebellar ataxia may permit further understanding of the role of glutamate-induced toxicity on neuronal death in these heredo-degenerative diseases.

Animals↗
PubMed1999

Dystonia musculorum mutation and myosin heavy chain expression in skeletal and cardiac muscles.

This study evaluated the influence of dystonia musculorum (dt) mutation, characterized by spinocerebellar fibers degeneration, on cardiac and skeletal muscles: one respiratory (diaphragm, Dia), three masticatory (anterior temporalis, AT; masseter superficialis, MS; and anterior digastric, AD), one hindlimb (soleus, S), tongue (T), and one cardiac (ventricle, V). Body and muscle weight, muscle protein content, and myosin heavy chain (MHC) isoforms relative expression were then compared in dt mutant mice and in normal mice, according to sex. Male body and muscle weight was always greater than that of females, but there was no specific muscle difference in females. dt mutant mice showed a reduced whole body growth but no specific muscle atrophy, as well as a global decrease in muscle protein content that made muscles more fragile. dt mutation induced a global reduction of muscle protein concentration, whereas a general influence of sex could not be disclosed. Concerning MHC relative composition, all the muscles were fast-twitch: Dia, AT, MS, AD, S, and T expressed predominantly the fast type 2 MHC isoforms, whereas V contained only MHC alpha, also a fast MHC. Female muscles were slower than male muscles, except for S, which was faster. However, classification of muscles in terms of shortening velocity was very different in normal males and females. In other respects, dt mutant muscles were slower and consequently more fatigue resistant than normal, except for S, which became faster and less fatigue resistant. dt mutation exhibits then a specific effect on this continually active postural muscle. In the other muscles, global increased fatigue resistance could constitute an adaptive response to work requirements modifications linked to the muscle damage. It should be noted that a developmental MHC (neonatal) was present in female dt AD. Innervation, which influences muscle structure, is altered in dt mutant and could be another causal factor of the fast-to-slow MHC switches. It appears that dystonin, the dt gene product, is very important in maintaining the structural integrity of both cardiac and skeletal muscle and in its absence, the muscle becomes more fragile and is damaged by modified activity.

Animals↗
PubMed1999

Motor coordination and spatial orientation are affected by neurofilament maldistribution: correlations with regional brain activity of cytochrome oxidase.

NFH-LacZ transgenic mice are characterized by an early accumulation of the neurofilament cytoskeleton in the cell bodies of neurons with age-associated abnormalities of motor neurons and cerebellar Purkinje cells. In comparison to normal littermate controls, irrespective of age (3 and 12-20 months), NFH-LacZ transgenic mice had a lower number of rears in an open field, deficiencies in some motor-coordination tests, and a higher number of quadrant entries and escape latencies while swimming toward a visible platform. Decreased cytochrome oxidase activity in the lateral reticular nucleus of NFH-LacZ mice was associated with poor performance in two motor coordination tests. Lower metabolic activity in the lateral reticular nucleus may be secondary to previously described cerebellar abnormalities, leading to deficient motor control. The dramatic cytoskeletal perturbation characterizing NFH-LacZ mice affects only selective neuronal populations and results in selective behavioral deficits, which can be correlated with regional brain metabolic activity.

Aging↗
PubMed1999

Effects of electrolytic lesions of the lateral pallidum on motor coordination, spatial learning, and regional brain variations of cytochrome oxidase activity in rats.

In view of recent theories suggesting a role for basal ganglia circuits in motor control and cognition, rats with bilateral electrolytic lesions of the lateral part of the globus pallidus were compared with control rats on motor coordination tasks and spatial learning in the Morris water maze. By comparison with sham-operated controls, rats with lesions of the lateral pallidum were impaired during acquisition of the rotorod task. Deficits were observed in a wooden beam task, but not in hole-board and suspended string tests. In addition, lesioned rats were impaired during acquisition of place learning but not of visuomotor guidance in the Morris water maze. Alterations of brain metabolism, as assessed by cytochrome oxidase activity, were found in three regions of lesioned rats, the subthalamic nucleus, the superior colliculus, and the centromedial thalamus of lesioned rats, probably as a result of interrupted neocortico-basal ganglia circuitry as a secondary consequence of the primary lesion.

Animals↗
PubMed1999

Regional brain distribution of noradrenaline uptake sites, and of alpha1-alpha2- and beta-adrenergic receptors in PCD mutant mice: a quantitative autoradiographic study.

The mouse "Purkinje cell degeneration" (pcd) is characterized by a primary loss of Purkinje cells, as well as by retrograde and secondary partial degeneration of cerebellar granule cells and inferior olivary neurons; this neurological mutant can be considered as an animal model of human degenerative ataxia. To determine the consequences of this cerebellar pathology on the noradrenergic system, noradrenaline transporters as well as alpha1-, alpha2- and beta-adrenergic receptors were evaluated by quantitative ligand binding autoradiography in adult control and pcd mice using, respectively, [3H]nisoxetine, [3H]prazosin, [3H]idazoxan and [3H]CGP12177. In cerebellar cortex and deep nuclei of pcd mutants, [3H]nisoxetine labelling of noradrenaline transporters was higher than in control mice. However, when binding densities were corrected by surface area, they remained unchanged in the cerebellar cortex but associated with 25% and 40% lower levels of labelling of alpha1 and beta receptors, as well as a very important increase (275%) of alpha2 receptors. In deep cerebellar nuclei, surface corrections did not reveal any changes either in transporter or in receptor densities. Higher densities of [3H]nisoxetine labelling were found in several regions related with the cerebellum, namely inferior olive, inferior colliculus, vestibular, reticular, pontine, raphe and red nuclei, as well as in primary motor and sensory cerebral cortex; they may reflect an increased noradrenergic innervation related to motor adjustments for the cerebellar dysfunction. Increased [3H]nisoxetine labelling was also measured in vegetative brainstem regions and in dorsal hypothalamus, implying altered autonomic functions and possible compensation in pcd mutants. Other changes found in extracerebellar regions affected by the mutation, such as thalamus and the olfactory system implicated both noradrenaline transporters and adrenergic receptors. In contrast to the important alterations of the noradrenergic system in cerebellar cortex, the lack of receptor changes in deep cerebellar nuclei suggests that local adaptations may be sufficient to minimize the consequence of the cerebellar atrophy on motor control. An intense labelling by [3H]idazoxan of the inner third of the molecular layer was a novel, albeit unexplained finding, and could represent a postsynaptic subset of alpha2-adrenergic receptors.

Adrenergic alpha-Antagonists↗
PubMed1998

Brain dopamine and amino acid concentrations in Lurcher mutant mice.

Lurcher mutant mice are characterized by massive degeneration of the cerebellum, including Purkinje cells and granule cells, as well as for the loss of neurons from the inferior olive. Concentrations of dopamine and two of its metabolites and of several amino acid neurotransmitters were determined in the cerebellum and in other brain regions of these mutants. By comparison to wild-type mice of the same background strain, glutamate and taurine concentrations were reduced in the Lurcher cerebellum. No decrease was found for aspartate, gamma-aminobutyric acid (GABA), glycine, as well as dopamine and its metabolites. Moreover, no neurochemical alterations occurred in the brain stem, thalamus, or neostriatum of Lurcher mutants. A selective reduction of glutamate concentration was found in the hippocampus, while all amino acids measured were decreased in the entorhinal-piriform areas. These results indicate region-selective reductions of neurotransmitter concentrations in a mouse mutant with a defined cerebellar cortical pathology.

Amino Acids↗
PubMed1998

Regional brain variations of cytochrome oxidase activity and motor coordination in Lurcher mutant mice.

Lurcher mutant mice are characterized by massive degeneration of cerebellar Purkinje cells and granule cells and by deficits in motor coordination. Regional brain variations of cytochrome oxidase (CO) activity were analyzed to identify those brain regions with abnormal metabolic activity as a secondary consequence of the cerebellar atrophy and to establish the relationship between CO activity and motor deficits. Lurcher mutants had higher CO activity in all three cerebellar deep nuclei than normal littermate controls of the same background strain. Higher CO activity was also found in Lurcher mutants in brain regions directly connected to the cerebellum, such as the lateral vestibular nucleus, the cochlear nucleus, the red nucleus, the ventrolateral thalamus, the dorsal raphe, the interpeduncular nucleus, and the inferior colliculus. By contrast, there was a sharp decrease in CO activity in the inferior olive. As for brain regions not directly connected to the cerebellum, higher CO activity was observed in the trigeminal motor nucleus and the CA1 molecular layer of the hippocampus, which highlights probable transsynaptic alterations as a secondary consequence of cerebellar atrophy. A positive correlation between CO activity in the red nucleus and latencies before falling in two motor-coordination tests indicates that a compensatory increase of metabolic activity in a cerebellar efferent region is associated with improved behavior.

Animals↗
PubMed1998

Grooming in Lurcher mutant mice.

Lurcher mutant mice, characterized by degeneration of cerebellar Purkinje cells and granule cells, were compared to normal littermate controls for different facets of grooming and nongrooming behaviors after a brief period of water immersion. By comparison to normal controls, the number and the duration of several grooming components were decreased in Lurcher mutant mice, namely, licking the forelimb, the abdomen, the back, and the hindlimb. By contrast, the number and duration of body-shaking episodes were not reduced. Lurcher mutants had fewer grooming elements for bouts with at least five elements. However, the serial organization of grooming, as determined by the order of appearance of grooming elements, was maintained in Lurcher mutants. These results indicate that the cerebellar cortex is involved in the appearance of various grooming elements but not in the organization of the cephalocaudal sequence.

Analysis of Variance↗
PubMed1998

Distribution of dopamine transporters in basal ganglia of cerebellar ataxic mice by [125I]RTI-121 quantitative autoradiography.

Dopamine (DA) uptake sites, or transporters, were examined with [125I]RTI-121 in mutant mice that exhibit motor control deficits, namely weaver, lurcher and dystonia musculorum. In lurcher mice, the distribution of [125I]RTI-121 binding was similar to controls, except for a decrease in the subthalamic nucleus. For dystonia musculorum mice, the labelling presented no differences between controls and mutants, except for decreases in the dorsal half of caudal neostriatum and in the ventral tegmental area. Moreover, in this mutant the left rostral neostriatum DA transporters were reduced, when compared to the right counterpart. In weaver heterozygote (wv/+) mice, the distribution and density gradients of [125I]RTI-121 labelling were similar as in their controls, except in caudal neostriatum, where binding was slightly higher. In contrast, the weaver homozygote (wv/wv) showed important decreases in labelling of the dorsal quadrant of rostral neostriatum as well as of the dorsal half of caudal neostriatum, where the reductions of binding densities were of 65% to 70%, respectively. There were also slight decreases in [125I]RTI-121 binding in olfactory tubercles as well as in subthalamic nucleus, but only in wv/wv mice. In substantia nigra pars compacta and ventral tegmental area of wv/wv mice the labelling was lower; however, while the 60% decrease in labelling in substantia nigra was highly significant, the 30% reduction in ventral tegmental area did not attain statistical significance. In summary, in the ataxic neurological mutant mice studied, important reductions of DA transporters were documented only for the weaver mice, the cerebellar mutant presenting, besides its cerebellar pathology, a known degeneration of mesencephalic dopaminergic neurons. The results rule out major alterations of the central DA systems in lurcher and dystonia musculorum, and are compatible with the hypothesis that the dopaminergic abnormalities of weaver mutants are not secondary to cerebellar atrophy, but may be a direct consequence of the abnormal weaver gene expressed by DA neurons leading to their apoptotic death.

Animals↗
PubMed1998

Regional brain variations of cytochrome oxidase activity and motor coordination in hot-foot mutant mice.

Hot-foot mutant mice are characterized by defective arborization of Purkinje cell dendrites, resulting in ataxia of gait and deficits of equilibrium. Regional brain variations of cytochrome oxidase (CO) activity were analysed for the purpose of identifying those brain regions with abnormal metabolic activity as a secondary consequence to the cerebellar alteration. In addition, the possible relation between CO activity and motor deficits was evaluated. By comparison to normal littermate controls of the same background strain, hot-foot mutants had higher CO activity in the molecular layer of the cerebellum, the ventrolateral and midline thalamic nuclei, as well as in the frontal eye field. There was no other alteration of CO activity in the hot-foot brain. No linear correlation was discerned between CO activity in the molecular layer of the cerebellum and the ventrolateral and midline nuclei on one hand, and motor coordination performance on the other. These results indicate regionally selective abnormalities of metabolic activity in a cerebellar mutant with defective dendritic arborization of the Purkinje cell.

Anatomy, Cross-Sectional↗
PubMed1996

Regional distribution of the 5-HT innervation in the brain of normal and lurcher mice as revealed by [3H]citalopram quantitative autoradiography.

The neurological cerebellar mutant lurcher is characterized by a primary degeneration of Purkinje cells as well as retrograde secondary partial degeneration of cerebellar granule cells and inferior olivary neurons. Since serotonin (5-HT) has been implicated in the modulation of excitatory amino acid systems of the cerebellum, the 5-HT innervation of the normal and lurcher mice was examined by quantifying uptake sites using [3H]citalopram autoradiography, and by biochemical assays of the indoles 5-HT, 5-hydroxy-L-tryptophan and 5-hydroxyindole-3-acetic acid using high-performance liquid chromatography. Comparable results were found between [3H]citalopram binding and 5-HT tissue concentrations in different brain regions. The highest [3H]citaslopram labelling was observed in defined structures of the mesencephalic and upper pontine regions, in limbic strutures, in hypothalamus and in discrete thalamic divisions, while the lowest labelling of uptake sites was documented in cerebellum and brainstem reticular formation. In lurcher mutants, the histology confirmed cell degeneration and the reduction in width, leading to 65%, 45% and 25% atrophies of total cerebellum, deep nuclei and inferior olivary nucleus, respectively. The [3H]citalopram labelling corrected for surface loss was 45% and 20% higher to cerebellar deep nuclei and red nucleus, respectively, but remained unchanged in the cerebellar cortex and inferior olivary nucleus. Moreover, higher labelling was found in nucleus raphe dorsalis, ventral tegmental area, inferior colliculus, locus coeruleus, pontine central grey and anterior thalamic nuclei, areas known to be part of cerebellar afferent and efferent systems. The present results indicate that in such pathological conditions as described for the lurcher mutant, the 5-HT system may modulate motor function not only at the level of the cerebellum, but also in other forebrain structures functionally related to the motor system.

Animals↗
PubMed1993

An unexpected role of the cerebellum: involvement in nutritional organization.

The influence of cerebellectomy in nutritional function was studied in the rat. Feeding behavior and analyses of lipids, proteins, nitrogen, and catecholamines in fecal and urinary excreta and in plasma were studied in 20 cerebellectomized, 20 sham operated, and 20 control animals. The results demonstrate that feeding behavior (quantitative rates of daily absorbed food, body weight, and the choice of the nutriment form) was lower in cerebellectomized animals compared to sham operated and control animals. Rates of steatorrhea and urinary levels of vanylmandelic acid, homovanillic acid, and metanephrine were higher in cerebellectomized animals while plasma levels of proteins, fatty acids, and glycerol were lower. Thus, the cerebellum is involved in nutritional regulation in the rodent.

Animals↗
PubMed1990

[Primary trigemino-cerebellar afferents demonstrated by the method of fluorescent retrograde double labeling in rats].

Two axonally transported fluorescent substances, Granular Blue and Nuclear Yellow, were applied in the mandibular nerve and in the entire half of ipsilateral cerebellar cortex respectively. Observations of serial slices by using fluorescent photonic microscope showed double marked cells in the caudal part of homolateral trigemino-mesencephalic nucleus. Cells body had a 28-35 microns diameter and showed an oval-shaped and a pseudo-unipolar type. Numbers of neurons were no more than 10-15 per animal. There was no indication of double coloured cells either in the trigeminal ganglion or in the adjacent bulbo-reticulo-pontic regions. It is concluded that identified neurons have their origin into periodontical structures. They bring the proof of non-vestibular direct cerebellar pathways.

Animals↗
PubMed1986

Co-operativity value of DNA RecA protein interaction. Influence of the protein quaternary structure on the binding analysis.

We show that an erroneous estimation of the quaternary structure of free protein distorts the quantitative analysis of its interaction with DNA, affecting especially the co-operativity value found. This could explain the discrepancy reported for the co-operativity value of the RecA-DNA interaction. The large cluster observed by electron microscopy indicates a very high co-operativity, whereas analysis of the binding isotherm indicates a moderate one, on the assumption of monomer. But if RecA is a large oligomer, the latter analysis would give a much higher co-operativity value and the former a smaller one, and they would be in accordance. Our sedimentation and light-scattering experiments suggest an oligomerization of about 30-mer or more, and support this explanation.

Allosteric Regulation↗