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Biomedical subjects

M Baldy-Moulinier

Publications and source records attributed to M Baldy-Moulinier.

At least 19 recordsLinked to original sources
PubMed1997

Lack of association between juvenile myoclonic epilepsy and GABRA5 and GABRB3 genes.

Alpha 5 and beta 3 GABAA receptor genes are major candidates for epilepsy, as they code for subunits of the most important human inhibitory neurotransmitter. Moreover, they are located within a region of the human genome previously implicated in disorders including epilepsy. We carried out an association study between dinucleotide repeat polymorphisms in these two genes and juvenile myoclonic epilepsy (JME). JME is the most common idiopathic epilepsy and is characterized by a complex mode of inheritance. We did not find significant differences between controls and patients for allele or genotype frequencies.

Adult↗
PubMed1997

Allelic heterogeneity of Mediterranean myoclonus and the cystatin B gene.

Mediterranean myoclonus is a progressive myoclonus epilepsy with autosomal recessive inheritance. Another form has been described in Finland, the so-called Baltic myoclonus. Mediterranean myoclonus and Baltic myoclonus are also known as Unverricht-Lundborg disease. Linkage analyses have shown that the genes for both these forms of myoclonus are closely linked to 21q22.3 DNA markers, suggesting that they are caused by mutations at the same locus (EPM1). Recently, two heterozygous mutations were found in the cystatin B gene in patients with Unverricht-Lundborg disease. We report recombinational and linkage disequilibrium mapping of EPM1, and cystatin B gene sequencing, in 14 consanguineous pedigrees with Mediterranean myoclonus. Linkage to 21q22.3 DNA markers was observed in all these families. Haplotype analysis suggests that a common mutation segregates within these pedigrees, and that this mutation is different from the common one responsible for the Finnish form of Unverricht-Lundborg disease. No mutation was found in the exons or splice junctions of the cystatin B gene in the 14 pedigrees.

Base Sequence↗
PubMed1997

Linkage mapping of benign familial infantile convulsions (BFIC) to chromosome 19q.

Benign familial infantile convulsions (BFIC) are an autosomal-dominant epileptic syndrome characterized by an age of onset within the first year of life. Although they were first reported in families of Italian descent, BFIC have also been described in non-Italian families. We have mapped the BFIC gene to chromosome 19 by linkage analysis in five Italian families with a maximum two-point lod score of 6.36 at D19S114; maximum multipoint lod scores > 8 were obtained for the interval D19S250-D19S245. BFIC are therefore the third idiopathic partial epileptic syndrome to be mapped on the human genome.

Chromosome Mapping↗
PubMed1997

Identification of mutations in cystatin B, the gene responsible for the Unverricht-Lundborg type of progressive myoclonus epilepsy (EPM1).

Progressive myoclonus epilepsy (EPM1) is an autosomal recessive disorder, characterized by severe, stimulus-sensitive myoclonus and tonic-clonic seizures. The EPM1 locus was mapped to within 0.3 cM from PFKL in chromosome 21q22.3. The gene for the proteinase inhibitor cystatin B was recently localized in the EPM1 critical region, and mutations were identified in two EPM1 families. We have identified six nucleotide changes in the cystatin B gene of non-Finnish EPM1 families from northern Africa and Europe. The 426G-->C change in exon 1 results in a Gly4Arg substitution and is the first missense mutation described that is associated with EPM1. Molecular modeling predicts that this substitution severely affects the contact of cystatin B with papain. Mutations in the invariant AG dinucleotides of the acceptor sites of introns 1 and 2 probably result in abnormal splicing. A deletion of two nucleotides in exon 3 produces a frameshift and truncates the protein. Therefore, these four mutations are all predicted to impair the production of functional protein. These mutations were found in 7 of the 29 unrelated EPM1 patients analyzed, in homozygosity in 1, and in heterozygosity in the others. The remaining two sequence changes, 431G-->T and 2575A-->G, probably represent polymorphic variants. In addition, a tandem repeat in the 5' UTR (CCCCGCCCCGCG) is present two or three times in normal alleles. It is peculiar that in the majority of patients no mutations exist within the exons and splice sites of the cystatin B gene.

Amino Acid Sequence↗
PubMed1997

[Clinical study of familial forms of amyotrophic lateral sclerosis. Review of the literature].

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder involving both upper and lower motor neurons. The disease is possibly due to several factors, including a genetic one. This is supported by the existence of 5 to 10 p. 100 familial cases. In these pedigrees, the transmission is autosomal dominant, with a high penetrance (> 90 p. 100). We studied the phenotypes of these familial cases, in reviewing the literature on familial ALS (FALS). It has been noted that FALS are heterogeneous, with different age of onset, site of onset and disease duration. Moreover, in FALS, onset is earlier than in the sporadic form (48 vs 60 years, as usually reported in the literature). We also frequently noted sensory disorders (20 p. 100), onset on the lower limbs (46 p. 100) and decreased or absent ankle-jerks (75 p. 100) in FALS patients.

Age Factors↗
PubMed1996

Early postnatal muscle contractile activity regulates the carbonic anhydrase phenotype of proprioceptive neurons in young and mature mice: evidence for a critical period in development.

Carbonic anhydrase activity, a marker of mouse proprioceptive neurons in adult dorsal root ganglia, is first detectable in the perinatal period, increases until postnatal day 60 and remains stable in adulthood. The onset of carbonic anhydrase staining begins after the neurons have made connections with their targets suggesting that neuron-target interactions regulate carbonic anhydrase phenotype development. To examine this possibility, we first analysed carbonic anhydrase expression in mdx mice which are characterized by a massive but reversible degeneration of skeletal muscle concomitant with the carbonic anhydrase ontogenesis. Neuronal carbonic anhydrase expression in mdx mice stopped developing when the period of muscular degeneration-regeneration began. Furthermore this alteration persisted during adulthood. We then analysed carbonic anhydrase expression in fifth lumbar dorsal root ganglion of developing control mice before and after surgical procedures that might interfere with central and peripheral target influences on dorsal root ganglion neurons. Central disconnection (dorsal rhizotomy) did not affect the development of carbonic anhydrase activity. Disrupting neuron-peripheral target interactions by sciatic nerve transection or blocking muscle contraction by tenotomy stopped the development of neuronal carbonic anhydrase content. Finally, recovery was monitored following sciatic nerve crush. In adults, recovery of carbonic anhydrase activity was obtained after functional recuperation; similar manipulations during the first month of life induced irreversible alteration of the carbonic anhydrase phenotype. These results show that the development of carbonic anhydrase activity in proprioceptive neurons is regulated by neuron-muscle interactions (i.e. muscle contraction). They also provide evidence for a critical period in the development of the carbonic anhydrase phenotype. We suggest that these two mechanisms are responsible for the altered carbonic anhydrase phenotype of the dorsal root ganglion neurons in mdx mice, a model of human muscular dystrophy.

Age Factors↗
PubMed1996

Opposite developmental regulation of P- and Q-type calcium currents during ontogenesis of large diameter mouse sensory neurons.

Analysis of neuronal development has emphasized the importance of voltage-activated Ca2+ currents during the initial period of differentiation. We investigated non-N, non-L Ba2+ currents through Ca2+ channels in freshly dissociated large diameter embryonic mouse dorsal root ganglion neurons using the whole-cell patch-clamp technique. Two types of omega-agatoxin IVA-sensitive currents were clearly distinguished at embryonic day 13: a sustained P-type current blocked selectively at 30 nM (IC50 = 3nM) and an inactivating Q-type current blocked in the range 50-500 nM (IC50 = 120nM). The P-type Ca2+ current disappeared at day 15 whereas the Q-type Ca2+ current increased two- to three-fold during the same embryonic period. In contrast, the contribution of the non-L, non-N, omega-agatoxin IVA-resistant current (R-type) was constant during this developmental span. In conclusion, our results clearly show that P- and Q-type Ca2+ currents are differentially expressed during ontogenesis in large diameter dorsal root ganglion neurons. The developmental change, which occurs during the period of target innervation, could be related to specific key events such as natural neuron death and onset of synapse formation.

Animals↗
PubMed1996

Effects of an ethanolic extract of Desmodium adscendens on central nervous system in rodents.

This study investigates some pharmacological effects of the ethanolic extract of the leaves of Desmodium adscendens (Papillionaceae), a medicinal plant in the African traditional medicine, on the central nervous system. The plant extract induced hypothermia and had analgesic effect in mice. D. adscendens suppressed the tonic phase of convulsion and mortality induced by pentylenetetrazole (PTZ) in mice. In addition, the plant extract delayed the onset of PTZ forelimb clonus, and generalized limbic seizures induced by kainic acid. In contrast, the plant extract did not affect either tonic convulsion induced by maximal electroshock in mice or the progression of limbic seizures towards the status epilepticus in rats.

Acetates↗
PubMed1995

Suicidal behaviors and the tryptophan hydroxylase gene.

BACKGROUND: To determine whether the tryptophan hydroxylase gene (ie, the gene that codes for the rate-limiting enzyme in the metabolic pathway of serotonin) may be a susceptibility factor for suicidal behavior. METHODS: Genotypic and allelic frequencies at a polymorphic Ava II restriction site were revealed with the use of the complementary DNA tryptophan hydroxylase probe C2-38 in 62 suicide attempters. The psychiatric characteristics of these suicide attempters were determined using the Schedule for Affective Disorders and Schizophrenia-Lifetime version with modification for the study of anxiety disorders, and these characteristics were compared with those in 52 healthy controls. RESULTS: No association between tryptophan hydroxylase and suicidal behavior was detected. CONCLUSION: The tryptophan hydroxylase gene was not a susceptibility factor for suicidal behaviors in the group of suicide attempters in this study.

Alleles↗
PubMed1995

Dihydropyridines, phenylalkylamines and benzothiazepines block N-, P/Q- and R-type calcium currents.

We compared the effects of representative members of three major classes of cardiac L-type channel antagonists, i.e. dihydropyridines (DHPs), phenylalkylamines (PAAs) and benzothiazepines (BTZs) on high-voltage-activated (HVA) Ca2+ channel currents recorded from a holding potential of -100 mV in rat ventricular cells, mouse sensory neurons and rat motoneurons. Nimodipine (DHP), verapamil (PAA) and diltiazem (BTZ) block the cardiac L-type Ca2+ channel current (EC50: 1 microM, 4 microM and 40 microM, respectively). At these concentrations, the drugs could also inhibit HVA Ca2+ channel currents in both sensory and motor neurons. Large blocking effects (> 50%) could be observed at 2-10 times these concentrations. The omega -conotoxin-GVIA-sensitive (omega -CTx-GVIA, N-type), omega -agatoxin-IVA-sensitive (omega -Aga-IVA, P- and Q-types) and non-L-type omega -CTx-GVIA-, omega -Aga-IVA-insensitive (R-types) currents accounted for more than 90% of the global current. Furthermore, our data showed that omega -CTx-GVIA and omega -Aga-IVA spare L-type currents and have only additive blocking effects on neuronal HVA currents. We conclude that DHPs, PAAs and BTZs have substantial inhibitory effects on neuronal non-L-type Ca2+ channels. Inhibitions occur at concentrations that are not maximally active on cardiac L-type Ca2+ channels.

Animals↗
PubMed1995

Monitoring sodium methohexital distribution with [99mTc]HMPAO with single photon emission computed tomography during Wada test.

Twenty-five consecutive patients being considered for surgery for intractable epilepsy had intracarotid sodium methohexital procedures (ISM) as part of their evaluation. The lipophilic brain SPECT agent, [99mTc]hexamethylpropylene aminoxime (HMPAO), was administered intravenously during the procedure to determine the intracerebral distribution of methohexital. The validity of the ISM depends on consistent delivery of the anesthetizing agent to one hemisphere, including the mesial structures of the temporal lobe. To prevent postoperative language and memory deficits, correct interpretation of the test results supposes a reliable knowledge of which regions of the brain have been anesthetized. Currently, no absolute criteria allow determination of the level and topographical extent of the anesthesia. We compared results of HMPAO-SPECT with clinical and EEG video-monitoring data and with results of digital subtraction angiography (DSA) performed during the test. In all patients, the effect of SM was ipsilateral cerebral hypoperfusion on SPECT and crossed cerebellar diaschisis. The distribution of HMPAO varied from patient to patient. The delivery of SM to mesial temporal lobe structures was not constant. Using nonparametric tests, we demonstrated a statistically significant relationship between hypoperfusion on SPECT and duration of hemiplegia but not with the duration of aphasia. Hypoperfusion on SPECT was also related to the onset and duration of drug-induced delta activity on EEG. SPECT showed a statistically different distribution of SM in the brain from that predicted with DSA. We present our experience with HMPAO-SPECT use for mapping the distribution of methohexital's effects during the ISM (Wada test). We confirm the results of previous studies that SPECT assessment may be an excellent way of determining the distribution of barbiturate during the examination. It increases confidence in interpreting results of speech and memory testing by detecting either contralateral diffusion of the drug due to crossflow between hemispheres or insufficient quantitative delivery to the homolateral hemisphere.

Adult↗
PubMed1994

Some neuropharmacological effects of an ethanolic extract of Maprounea africana in rodents.

The ethanolic extract of the leaves of Maprounea africana (Euphorbiaceae), a medicinal plant in the Congolese traditional medicine, induced hypothermia and reduced the latency to the loss of the righting reflex and prolonged the sleeping time induced by pentobarbital in mice. It also significantly delayed the onset of clonic convulsions induced by pentylenetetrazole in mice. However, the extract did not affect either generalized convulsions induced by maximal electroshock and picrotoxin or limbic status epilepticus produced by pilocarpine and kainic acid.

Animals↗
PubMed1994

Some pharmacological effects of an ethanolic extract of Trema guineensis on the central nervous system in rodents.

The present study investigates some neuropharmacological effects of an ethanolic extract of the leaves of Trema guineensis (Ulmaceae), a medicinal plant of central Africa. Intraperitoneal administration of the extract induced hypothermia. In addition, the extract significantly shortened the latency to sleep and prolonged the duration of sleeping time induced by sodium pentobarbital in mice. Moreover, T. guineensis significantly delayed the onset of clonic seizures induced by pentylenetetrazole in mice. In contrast, T. guineensis did not affect convulsions induced by maximal electroshock and picrotoxin in mice nor status epilepticus produced by pilocarpine and kainic acid in rats.

Africa, Central↗
PubMed1993

Developmental regulation of carbonic anhydrase expression in mouse dorsal root ganglia.

The development of proprioceptive neurons in mammalian dorsal root ganglia (DRG) remains poorly documented since few specific markers for these neurons are known. Recent studies suggest that carbonic anhydrase (CA) is a specific marker of this functionally defined neuronal population. The present study was designed to investigate the development of CA staining in sensory neurons. We investigated CA reactivity in mouse lumbar DRGs from embryonic day 13 (E13) to postnatal day 100 (P100) using a modified cytoenzymatic Hansson method. Neuronal CA reactivity was first detected during the perinatal stage (1-3% of DRG neurons) and increased progressively from P0 to P60 when it reached a plateau (about 30-33% of DRG neurons). Statistical morphometric analysis was used to define whether CA staining identifies the same population(s) during development. The results demonstrated that, whatever the stage of development, reactive neuronal cells are included in the well-defined large type A population. The possibility that neuronal CA expression is a reliable marker of the 'functional activity' of the proprioceptive neurons in mammals is discussed. The late development expression of the enzyme (after target innervation) raises the possibility of a regulation of the CA phenotype by neuron-target interactions.

Animals↗
PubMed1993

Skeletal muscle extract and nerve growth factor have developmentally regulated survival promoting effects on distinct populations of mammalian sensory neurons.

Neurotrophic factors appear to be relevant to the therapy of degenerative diseases as well as neural regeneration. In this respect, we have investigated the neurotrophic effects of skeletal muscle extract on DRG neuron survival by examining the survival and neurite outgrowth promoting activity of factor(s) present in skeletal muscle extracts (SME) on dissociated cultures of embryonic or early postnatal mouse dorsal root ganglion (DRG) sensory neurons. The numbers of surviving neurons resulting from SME addition increased continuously from embryonic day 13 (15%) to birth (55%), then decreased up to 7 days after hatching (0%). Preliminary characterization of the factor(s) present in SME suggests that the active molecule is a protein different from the known neurotrophic factors NGF, BDNF, NT3, CNTF, and bFGF, and that its neurotrophic effect is not mediated by direct interaction with the substratum.

Animals↗
PubMed1993

Fasting plasma and CSF amino acid levels in amyotrophic lateral sclerosis: a subtype analysis.

Data from the literature about plasma and CSF amino acid (AA) levels in amyotrophic lateral sclerosis (ALS) remain controversial. To refine such analyses we used HPLC, and report a study of plasma and CSF AA concentrations in patients with ALS, the type of the disease (spinal and bulbar onset) being precisely determined. In ALS, there is a decrease in the plasma levels of the large neutral amino acids (LNAA) alanine, isoleucine, leucine, methionine and tyrosine which was particularly striking in the bulbar type (p < 0.05). Plasma glutamate levels do not differ between ALS and controls, but are significantly increased in ALS with spinal onset and decreased in the bulbar type (p < 0.05 vs controls, p < 0.001 bulbar vs spinal). In CSF, the analysis of the whole ALS group shows no difference from controls. However, there is an increase of CSF serine, glutamine and alanine in ALS with spinal onset (p < 0.05). Our results do not support an abnormal profile of excitatory AA concentrations in ALS. The heterogeneous changes we observed, mainly concerning LNAAs, may be explained by a blood-CSF barrier disturbance in the disease. As AA levels clearly differ between ALS types, with low concentrations in bulbar ALS, this dual profile probably explains some of the discrepancies between previous studies.

Amino Acids↗