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Bruno Giros

Publications and source records attributed to Bruno Giros.

22 records · Page 2Linked to original sources
PubMed2003

[Genetics of autism: from genome scans to candidate genes].

The autistic disorder was firstly described by Leo Kanner sixty years ago. This complex developmental disability is characterized by social and communicative impairments and repetitive and stereotyped behaviours and interests. The prevalence of autism in the general population is about 1 in 1,000, with four males affected for one female. In approximately 15% of the cases, autism is associated with known genetic disorders, such as fragile X syndrome, tuberous sclerosis or Rett syndrome. Nevertheless, a recognised medical etiology can only be identified in a minority of cases. A higher recurrence risk in families with autistic subjects (45 times greater than the prevalence in the general population) and higher concordance for autism among monozygotic (60-90%) than dizygotic (0-10%) twins argue for a genetic predisposition to idiopathic autism. The past decade has been marked by an increased interest in the genetic basis of autism, with a series of multiple independent whole genome scans and chromosomal abnormalities studies. These analyses have pointed out several candidate regions on chromosomes 2q, 7q, 6q, 15q and sex chromosomes. These regions possess candidate genes that have been screened for mutations or association with autism. However, a clear involvement of a major susceptibility gene (or genes) in autism remains far from clear. The results from linkage studies and the clear drop in the concordance rates between monozygotic and dizygotic twins suggests that the genetic aetiology of autism is certainly heterogeneous (different genes in different families) and polygenic (more than one affected gene per individual). The almost finished sequence of the human genome and the generation of haplotype maps will shed light on the inter-individual genetic variability and will certainly increase the power and reliability of association studies for complex traits, such as autism.

Autistic Disorder↗
PubMed2002

A third vesicular glutamate transporter expressed by cholinergic and serotoninergic neurons.

Two proteins previously known as Na(+)-dependent phosphate transporters have been identified recently as vesicular glutamate transporters (VGLUT1 and VGLUT2). Together, VGLUT1 and VGLUT2 are operating at most central glutamatergic synapses. In this study, we characterized a third vesicular glutamate transporter (VGLUT3), highly homologous to VGLUT1 and VGLUT2. Vesicles isolated from endocrine cells expressing recombinant VGLUT3 accumulated l-glutamate with bioenergetic and pharmacological characteristics similar, but not identical, to those displayed by the type-1 and type-2 isoforms. Interestingly, the distribution of VGLUT3 mRNA was restricted to a small number of neurons scattered in the striatum, hippocampus, cerebral cortex, and raphe nuclei, in contrast to VGLUT1 and VGLUT2 transcripts, which are massively expressed in cortical and deep structures of the brain, respectively. At the ultrastructural level, VGLUT3 immunoreactivity was concentrated over synaptic vesicle clusters present in nerve endings forming asymmetrical as well as symmetrical synapses. Finally, VGLUT3-positive neurons of the striatum and raphe nuclei were shown to coexpress acetylcholine and serotonin transporters, respectively. Our study reveals a novel class of glutamatergic nerve terminals and suggests that cholinergic striatal interneurons and serotoninergic neurons from the brainstem may store and release glutamate.

Acetylcholine↗
PubMedDate not supplied

Augmented constitutive CREB expression in the nucleus accumbens and striatum may contribute to the altered behavioral response to cocaine of adult mice exposed to cocaine in utero.

Neuroadaptations occurring in the mesolimbic dopamine pathway following recurrent exposure to drugs of abuse have been correlated with a behavioral phenomenon known as behavioral sensitization. We have developed an animal model of prenatal cocaine exposure and, using a postnatal sensitization protocol, have examined the subsequent sensitivity of offspring to cocaine. Pregnant Swiss Webster dams were injected twice daily from embryonic day 8 to 17, inclusive, with cocaine (COC40: administered cocaine HCl at a dose of 40 mg/kg/day, and COC20: administered cocaine HCl at a dose of 20 mg/kg/day), or saline (SAL). The SPF40 group (saline pair-fed), a nutritional control group, was 'pair-fed' with COC40 dams. Activity was recorded for 30 min during a 3-day saline habituation, a 14-day 'initiation' phase, when animals received cocaine (15 mg/kg) or saline every other day, and following a 21-day 'withdrawal' period when all mice were challenged with cocaine. COC40 offspring, as compared with SAL controls, did not habituate to a novel environment, demonstrated increased cocaine-induced stereotypy on Coc 1 (first cocaine injection), and blunted locomotor sensitization on challenge as measured by the percentage of each animal's baseline locomotion. Tissue samples of the nucleus accumbens (NAc) and striatum (Str) of all four prenatal treatment groups were examined to determine whether alterations in the transcription factor CREB or glutamate receptor subunit, GluR1, induced by prenatal cocaine treatment may have contributed to the altered behavioral responses. Immunoblot quantitation revealed significantly increased constitutive CREB expression in the NAc and Str of COC40 mice as compared with SAL controls. Such alterations in constitutive CREB levels may contribute to some of the behavioral differences reported in adult mice exposed to cocaine in utero.

Animals↗