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J Mallet

Publications and source records attributed to J Mallet.

At least 109 records · Page 6Linked to original sources
PubMed1998

Tyrosine hydroxylase in the european eel (Anguilla anguilla): cDNA cloning, brain distribution, and phylogenetic analysis.

We report the isolation of a full-length eel tyrosine hydroxylase (TH) cDNA that is characterized by a long 3' untranslated region and by a diversity restricted to the 3' end owing to the differential use of three polyadenylation signals. The longest eel TH mRNA was distinctive in the presence of four pentameric elements (AUUUA) in the AU-rich 3' noncoding region. Such a diversity could provide the basis of posttranscriptional or translational regulation of eel TH gene expression. Comparison of the eel TH sequence with those of other aromatic amino acid hydroxylases (TH, tryptophan hydroxylase, and phenylalanine hydroxylase) and phylogenetic analysis confirmed that the N-terminal regulatory domain is highly divergent, contrasting with the conservation of the catalytic core of the enzyme. Molecular phylogenies including the available sequences of the three hydroxylase genes suggested that the duplication of their common ancestor occurred before the emergence of arthropods. The regional expression of the eel TH mRNA was studied by semiquantitative PCR, northern blots, and in situ hybridization and compared with the immunocytochemical localization of TH protein. The data showed that TH mRNA is mostly expressed in the olfactory and hypothalamic areas, whereas sparse TH-expressing cell bodies are present in the telencephalic region and brainstem. No labeling was detected in the mesencephalic area, in striking contrast with that found in amphibians and amniotes.

Amino Acid Sequence↗
PubMed1998

Induction of long-term potentiation in vivo regulates alternate splicing to alter syntaxin 3 isoform expression in rat dentate gyrus.

The regulation and specificity of the interactions between the proteins involved in neurotransmitter release are obvious targets for the cellular control of synaptic plasticity. Previous research has identified one of these proteins, syntaxin 1B, as a potential target for mediating the propagation of synaptic plasticity through neural networks. The expression of syntaxin 1B is modified in the hippocampus after the induction of long-term potentiation (LTP) and during learning. Here, we describe the identification of two other members of the syntaxin family from rat brain, syntaxins 3A and 3B, and show that they are generated from the same gene by alternate splicing. In situ hybridization and immunohistochemical staining confirm the expression of syntaxins 3A and 3B in the adult rat brain. The transcripts and proteins show a lower abundance but a similar pattern of expression as syntaxins 1A and 1 B. By using quantitative competitive PCR, we show that the mRNAs that encode syntaxins 1B and 3A are increased in dentate granule cells 6 h after the induction of LTP in vivo, whereas syntaxin 3B mRNA is decreased as rapidly as 30 min, and lasts for at least 6 h, after the induction of LTP. These findings identify coordinated changes in the expression of several syntaxin isoforms with different substrate specificities and suggest that regulation of the splicing machinery by LTP induction is one of the diverse strategies used during the long-term modification of the synapse in the vertebrate nervous system.

Alternative Splicing↗
PubMed1998

Retinoic acid regulates the developmental expression of dopamine D2 receptor in rat striatal primary cultures.

The time course of D2 receptor expression assessed by the levels of the corresponding binding sites and mRNA was studied in rat striatum during ontogenesis and in primary cultures of cells taken at embryonic day (E) 17 and postnatal day (P) 4. In the two experimental situations, the amount of D2 receptor mRNA and number of binding sites increased regularly from E16 to P15, indicating that expression of D2 receptors in striatal neurons occurs independently from a dopaminergic input. Incubation of striatal primary cultures with 10(-5) M retinoic acid significantly increased the level of D2 receptor mRNA, whereas thyroid hormone, vitamin D3, and steroid hormones (estradiol, testosterone, and corticosterone) had no effect. The transcriptional activity of the rat D2 receptor gene promoter region, which bears a retinoic acid-responsive element, was increased by retinoic acid in transfected C6 glioma cells but not in transfected MMQ prolactin cells. Thyroid hormone and vitamin D3 were not effective in either cell line. Finally, mutations of the putative retinoic acid-responsive element inhibited the transcriptional effect of retinoic acid. These results suggest that retinoic acid is a key factor in regulation of the embryonic onset of the dopaminergic D2 receptor.

Animals↗
PubMed1998

A tetranucleotide polymorphic microsatellite, located in the first intron of the tyrosine hydroxylase gene, acts as a transcription regulatory element in vitro.

The polymorphic HUMTH01 microsatellite, located in the first intron of the tyrosine hydroxylase gene is characterized by a tetranucleotide core motif. The 10 repeat allele of this microsatellite exhibits two sequence variants: an imperfect repeat and a perfect repeat. Here we present evidence that this tetrarepeat is endowed with regulatory properties. Constructions were made linking the 10 repetition alleles to the luciferase reporter gene under the control of a thymidine kinase minimal promoter. In transient transfection experiments in HeLa, PC12 and SK-NSH cell lines these repeated sequences increased the basal transcription up to 9-fold. This effect was independent of the sequence orientation, a feature characteristic of an enhancer element. In electrophoretic mobility shift assays these tetrameric repeated sequences form specific complexes with HeLa cell nuclear extracts. Competition experiments with heterologous sequences suggest that proteins of the Fos-Jun family may be involved in the formation of these complexes, although other unidentified transacting factors bind to these sequences. These results thus implicate the HUMTH01 microsatellite in the regulation of tyrosine hydroxylase gene expression. Tetrarepeated sequences of this type may constitute a new class of regulatory elements.

Alleles↗
PubMed1997

Relax promotes ectopic neuronal differentiation in Xenopus embryos.

We previously isolated a novel rat cDNA encoding a basic helix-loop-helix transcription factor named Relax, whose expression in the developing central nervous system is strictly limited to discrete domains containing precursor cells. The timing of Relax expression coincides with neuronal differentiation. To investigate the involvement of Relax in neurogenesis we tested whether Relax activated neural genes in the ectoderm by injecting Relax RNA into Xenopus embryos. We demonstrate that ectopic Relax expression induces a persistent enlargement of the neural plate and converts presumptive epidermal cells into neurons. This indicates that Relax, when overexpressed in Xenopus embryos, has a neuronal fate-determination function. Analyses both of Relax overexpression in the frog and of the distribution of Relax in the rat neural tube strongly suggest that Relax is a neuronal fate-determination gene.

Animals↗
PubMed1997

What initiates speciation in passion-vine butterflies?

Studies of the continuum between geographic races and species provide the clearest insights into the causes of speciation. Here we report on mate choice and hybrid viability experiments in a pair of warningly colored butterflies, Heliconius erato and Heliconius himera, that maintain their genetic integrity in the face of hybridization. Hybrid sterility and inviability have been unimportant in the early stages of speciation of these two Heliconius. We find no evidence of reduced fecundity, egg hatch, or larval survival nor increases in developmental time in three generations of hybrid crosses. Instead, speciation in this pair appears to have been catalyzed by the association of strong mating preferences with divergence in warning coloration and ecology. In mate choice experiments, matings between the two species are a tenth as likely as matings within species. F1 hybrids of both sexes mate frequently with both pure forms. However, male F1 progeny from crosses between H. himera mothers and H. erato fathers have somewhat reduced mating success. The strong barrier to gene flow provided by divergence in mate preference is probably enhanced by frequency-dependent predation against hybrids similar to the type known to occur across interracial hybrid zones of H. erato. In addition, the transition between this pair falls at the boundary between wet and dry forest, and rare hybrids may also be selected against because they are poorly adapted to either biotope. These results add to a growing body of evidence that challenge the importance of genomic incompatibilities in the earliest stages of speciation.

Animals↗
PubMed1997

Intrastriatal injection of an adenoviral vector expressing glial-cell-line-derived neurotrophic factor prevents dopaminergic neuron degeneration and behavioral impairment in a rat model of Parkinson disease.

Glial-cell-line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for adult nigral dopamine neurons in vivo. GDNF has both protective and restorative effects on the nigro-striatal dopaminergic (DA) system in animal models of Parkinson disease. Appropriate administration of this factor is essential for the success of its clinical application. Since it cannot cross the blood-brain barrier, a gene transfer method may be appropriate for delivery of the trophic factor to DA cells. We have constructed a recombinant adenovirus (Ad) encoding GDNF and injected it into rat striatum to make use of its ability to infect neurons and to be retrogradely transported by DA neurons. Ad-GDNF was found to drive production of large amounts of GDNF, as quantified by ELISA. The GDNF produced after gene transfer was biologically active: it increased the survival and differentiation of DA neurons in vitro. To test the efficacy of the Ad-mediated GDNF gene transfer in vivo, we used a progressive lesion model of Parkinson disease. Rats received injections unilaterally into their striatum first of Ad and then 6 days later of 6-hydroxydopamine. We found that mesencephalic nigral dopamine neurons of animals treated with the Ad-GDNF were protected, whereas those of animals treated with the Ad-beta-galactosidase were not. This protection was associated with a difference in motor function: amphetamine-induced turning was much lower in animals that received the Ad-GDNF than in the animals that received Ad-beta-galactosidase. This finding may have implications for the development of a treatment for Parkinson disease based on the use of neurotrophic factors.

Adenoviridae↗
PubMed1997

AP-1 mediates trans-synaptic induction of tyrosine hydroxylase gene expression in adrenal medulla but not in superior cervical ganglia.

Reserpine treatment leads to a rapid trans-synaptic increase of the tyrosine hydroxylase (TH) gene transcription rate and mRNA levels in catecholaminergic tissues including the adrenal medulla (AM) and the superior cervical ganglia (SCG). In the AM, the formation of a specific protein complex with the TPA-responsive element located in the proximal region of the TH gene was enhanced between 30 min and 8 hr following the injection. This complex appears to contain a member of the Fos family and an antigenically related Jun protein. Moreover, the prolonged and enhanced expression of the c-Fos protein in the AM and its phosphorylation are likely to contribute to the increased TH transcription following reserpine treatment. Most strikingly, in the SCG, the trans-synaptic induction of TH transcription is transduced by totally different mechanisms, since no AP-1 complex and only minute amounts of c-Fos immunoreactivity were detected. Our study provides the first demonstration that, following the same stimulus, the induced expression of a single gene is mediated by different cis- and trans-acting factors in two distinct tissues sharing the same embryonic origin.

Adrenal Medulla↗
PubMed1997

An ADP-ribosylation-factor(ARF)-like protein involved in regulated secretion.

A rat ADP-ribosylation factor(ARF)-like protein named ARL184 was identified by cDNA cloning. The corresponding recombinant protein had an apparent molecular mass of 22,000. The deduced amino acid sequence had 55% identity with the human ARL1 and four functional GTP-binding sites. Immunofluorescent confocal microscopy studies showed that ARL184 was present in the cytosol as well as in the Golgi apparatus, raising the possibility that it has a role in a secretory pathway. The involvement of this ARF-like protein in secretion was confirmed by demonstrating that ARL184 potentiated acetylcholine release in stably transfected PC12 cells. Collectively these results suggest that this ARL protein is a component of a regulated secretory pathway involved in Ca2(+)-dependent release of acetylcholine.

ADP-Ribosylation Factors↗
PubMed1997

Prevention of motoneuron death by adenovirus-mediated neurotrophic factors.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motoneurons, and has no effective treatment. Experimental studies in rodents have shown that motoneurons respond to a variety of molecules including brain-derived neurotrophic factor (BDNF). and the glial-cell line-derived neurotrophic factor (GDNF). Here we investigated the neuroprotective effect of these growth factors, encoded by an adenovirus, on the death of axotomized facial motoneurons in newborn rats. We used a new gene therapy strategy that involves gene transfer to motoneurons by intramuscular injection of an adenoviral vector, which is retrogradely transported from injected target muscle (Finiels et al.,: NeuroReport 7:373-378, 1995). A significant increased survival of motoneurons was observed in animals pretreated with adenovirus encoding BDNF (34.5%, P < 0.05) ou GDNF (41.9%, P < 0.05) 1 week after axotomy. These results indicate that pretreatment with BDNF or GDNF, using this therapeutic strategy, is able to prevent the massive death of motoneurons that normally follows axotomy in the neonatal period, opening new perspectives to limit neuronal death in degenerative disorders.

Adenoviridae↗
PubMed1997

Relax, a novel rat bHLH transcriptional regulator transiently expressed in the ventricular proliferating zone of the developing central nervous system.

A number of basic helix-loop-helix containing proteins have been shown to be required for neural development at different sites or times. Here, Relax, a novel rat basic helix-loop-helix transcriptional regulator, has been isolated and characterized. Analysis of the temporal and spatial distributions shows that the Relax transcripts are detected exclusively in the central nervous system, in discrete regions from embryonic day 11.5 to 18.5. Most strikingly, Relax is expressed along two major boundaries that define the longitudinal axis in the spinal cord and the hindbrain and is a marker of the anterior tip of this axis in the forebrain. Relax-expressing cells are strictly localized in the ventricular zone of the neural tube, where neural progenitors originate. This unique pattern of expression suggests that Relax is involved in neural fate determination.

Animals↗
PubMed1997

Association of DNA polymorphism in the first intron of the tyrosine hydroxylase gene with disturbances of the catecholaminergic system in schizophrenia.

We examined whether there are clinical or biological differences in chronic schizophrenic patients sharing a rare variant allele (a perfect ten tetranucleotide repeats allele of the human TH01 microsatellite) in the tyrosine hydroxylase (TH) gene. For that purpose, clinical parameters (PANSS subscores) and plasma measurements (homovanillic acid and 3-methoxy-4-hydroxy-phenylglycol (MHPG)) were analyzed in five schizophrenic patients sharing the rare allele and 19 schizophrenic patients who did not possess this allele. The mean concentration of plasma HVA and plasma MHPG were significantly lower in the group of schizophrenic patients sharing the rare allele. No other group differences were observed between both groups. These results suggest that this TH gene polymorphism may be associated with disturbances of the catecholaminergic pathway.

Adult↗
PubMed1997

Adenovirus-mediated gene transfer to the central nervous system for Parkinson's disease.

Gene therapy is a potentially powerful approach to the treatment of neurological diseases. The discovery of neurotrophic factors inhibiting neurodegenerative processes and the isolation of genes encoding neurotransmitter synthesizing enzymes provide the basis for current gene therapy strategies for Parkinson's disease. Adenovirus vectors have been shown recently to allow efficient gene transfer to the brain. One of the advantages of recombinant adenovirus is that it can transduce both quiescent and actively dividing cells. Thus expression of transgenes in neurons using adenoviruses is possible after either direct in vivo gene transfer or ex vivo gene transfer. In vivo gene transfer, consisting of the direct intracerebral injection of genetic material, is a novel method that is particularly efficient with the adenoviral vector. Ex vivo gene transfer, combining gene transduction with intracerebral transplantation, is a way to improve the classical grafts which are limited by poor cell survival in Parkinson's disease. Probably because the brain is a partially immunologically privileged site, the expression of adenoviral vectors persists for several months with little inflammation. Recombinant adenoviruses are currently being improved, particularly by inactivating viral genes controlling the expression of immunodominant viral proteins.

Adenoviridae↗
PubMed1997

Manic depressive illness and tyrosine hydroxylase gene: linkage heterogeneity and association.

Several studies have implicated the tyrosine hydroxylase (TH) locus within the 11p15 region in susceptibility to manic depressive illness (MDI). This possibility was further investigated by both parametric (lod score) and nonparametric (affected-pedigree-member and a case-control study) methods of analysis in 11 French MDI families and in a sample of 200 unrelated subjects. Both types of analyses corroborate the implication of this locus, and positive lod scores were obtained in two families, which most likely reflects genetic heterogeneity. Statistical analyses were also performed including available data from published reports. These analyses, which allowed for genetic heterogeneity, substantiated our findings. The combined maximum lod score for all the families studied was 3.68 at theta = 0.00 (number of families: 36) assuming heterogeneity (alpha = 15%, P = 0.01). Taken together these results converge to suggest that the risk factors for MDI lie in the 11p15 region with TH being the most likely candidate gene.

Alleles↗
PubMed1997

In vivo adenovirus-mediated gene transfer for Parkinson's disease.

Gene therapy is a potentially powerful approach to the treatment of neurological diseases. Neurotransmitter synthesizing enzymes and neurotrophic factors inhibiting neurodegenerative processes provide the basis for current development of gene therapy strategies for Parkinson's disease. Recently, in vivo gene transfer to the brain has been developed using adenovirus vectors. One of the advantages of recombinant adenovirus is that it can transduce both quiescent and actively dividing cells, thereby allowing both direct in vivo gene transfer and ex vivo gene transfer to neural cells. The expression of adenoviral vectors persists for several months with little inflammation, probably because the brain is partially protected from the immune system. Recombinant adenoviruses are currently being improved, particularly by inactivating viral genes controlling the expression of immunodominant viral proteins. Novel therapeutic tools such as vectors for gene therapy have to be evaluated in terms of efficacy and safety for future clinical trials. These vectors still need to be improved to allow long-term and possibly regulatable expression of the transgene.

Adenoviridae↗
PubMed1997

Gene therapy for Parkinson's disease.

Gene therapy is a potentially powerful approach to the treatment of neurological diseases. The discovery of neurotrophic factors inhibiting neurodegenerative processes and neurotransmitter-synthesizing enzymes provides the basis for current gene therapy strategies for Parkinson's disease. Genes can be transferred by viral or nonviral vectors. Of the various possible vectors, recombinant retroviruses are the most efficient for genetic modification of cells in vitro that can thereafter be used for transplantation (ex vivo gene therapy approach). Recently, in vivo gene transfer to the brain has been developed using adenovirus vectors. One of the advantages of recombinant adenovirus is that it can transduce both quiescent and actively dividing cells, thereby allowing both direct in vivo gene transfer and ex vivo gene transfer to neural cells. Probably because the brain is partially protected from the immune system, the expression of adenoviral vectors persists for several months with little inflammation. Novel therapeutic tools, such as vectors for gene therapy have to be evaluated in terms of efficacy and safety for future clinical trials. These vectors still need to be improved to allow long-term and possibly regulatable expression of the transgene.

Adenoviruses, Human↗
PubMed1997

Quantitative analysis of tau protein-immunoreactive accumulations and beta amyloid protein deposits in the cerebral cortex of the mouse lemur, Microcebus murinus.

Recent studies have revealed the presence of tau protein-immunoreactive accumulations and beta amyloid protein (A beta) deposits in the cerebral cortex of the aged mouse lemur, Microcebus murinus. To examine the age-related evolution of these changes and compare their regional distribution to that reported for humans and nonhuman primates with Alzheimer's disease lesions, we performed a quantitative analysis of a large series of mouse lemurs aged from 1 to 13 years. The prevalence and density of tau protein-immunoreactive accumulations in the neocortex of this prosimian increased steadily with age. Neocortical areas were frequently affected even in young mouse lemurs, whereas the subiculum and entorhinal cortex were only involved occasionally in animals older than 8 years. As in anthropoid primates, diffuse A beta deposits were often observed in the cerebral cortex and amygdala of old mouse lemurs. Although all animals with diffuse A beta deposits had tau protein-immunoreactive accumulations in the neocortex, no correlation was found between the densities of these lesions in each area and among the areas studied. The age-dependent progression of tau protein-immunoreactive accumulations indicates that this prosimian may represent a valuable model for the study of the biochemical mechanisms of brain aging, while the relative sparing of hippocampus in mouse lemurs contrasts sharply with previous reports on neurofibrillary tangle formation in humans, and suggests that this animal may also be useful to investigate the biological characteristics of neuroprotection in this area. Furthermore, the present data indicate that A beta deposition in mouse lemurs is not age dependent, but occurs in a few vulnerable old animals.

Age Factors↗