La déficience intellectuelle (DI) et les troubles du spectre autistique (ASD) sont deux troubles neurodéveloppementaux (NDD) présentant de nombreux chevauchements génétiques et phénotypiques ainsi qu’un biais de sexe important, avec plus de garçons atteints (1,4x plus pour la DI et 4x plus pour l'ASD). Au sein de notre laboratoire, le taux de diagnostic des patients souffrant de DI et/ou d’ASD est significativement plus élevé chez les filles que chez les garçons. De façon surprenante, nous n’avons pas observé de différence significative entre filles et garçons au niveau de la proportion de mutations pathogènes sur le chromosome X (5,3% versus 7,6%), confirmant ainsi que les mutations causales totalement pénétrantes sur ce chromosome ne peuvent pas expliquer la totalité de l’excès de garçons atteints de DI ou d'ASD. Nous avons donc choisi d’étudier une autre des hypothèses, plus environnementale, qui pourrait rendre le cerveau masculin plus susceptible au développement de NDD : le rôle des androgènes au cours du développement du cerveau. J'ai étudié l’effet de ces hormones masculines dans des précurseurs neuronaux humains (hNSCs) et observé que les androgènes augmentent la prolifération des hNSCs et les protègent contre la mort cellulaire en conditions stressantes. J'ai également mis en évidence que les androgènes, via leur récepteur (le récepteur aux androgènes), régulent une centaine de gènes dans les hNSCs avec, parmi eux, un enrichissement en gènes connus pour être différentiellement exprimés chez les individus avec ASD (dont NRCAM et FAM107A). La régulation de ces gènes par les androgènes pendant le développement du cerveau pourrait ainsi participer à la sensibilité accrue du cerveau masculin, exposé à d'autres facteurs génétiques et environnementaux, à développer une NDD. / Intellectual disability (ID) and autism spectrum disorders (ASD) are two common neurodevelopmental disorders (NDD) with many genetic and phenotypic overlaps. Another common feature is the existence of a gender bias, very strong for ASD (4 males for 1 female) and notable for ID (1.4:1). In our team, the diagnostic yield of patients affected by ID with or wihout ASD is significantly higher in girls than in boys. Surprisingly, we did not observe a significant difference between girls and boys in the proportion of pathogenic mutations on the X chromosome (5.3% versus 7.6%), confirming that rare and fully penetrant mutations on this chromosome can not explain the totality this male bias observed in ID and ASD. We have therefore chosen to study another hypothesis, more environmental, which could make the male brain more susceptible to develop NDD: the role of androgens during brain development. I studied the effect of these male hormones in human neuronal precursors (hNSCs) and observed that androgens increase the proliferation of hNSCs and protect them against cell death under stressful conditions. I also showed that androgens, via their receptor (the androgen receptor), regulate a hundred genes in hNSCs with, among them, an enrichment of genes known to be differentially expressed in individuals with ASD (e.g NRCAM and FAM107A). The regulation of these genes by androgens during brain development could thus contribute to the increased sensitivity of the male brain, exposed to other genetic and environmental factors, to develop an NDD.

Made available in DSpace on 2016-04-29T13:31:03Z (GMT). No. of bitstreams: 1 Naiara Roberta Vicente de Matos.pdf: 616830 bytes, checksum: b2525eb877dec6b9920f61fea3acfd42 (MD5) Previous issue date: 2013-06-14 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This research aims to analyze, based on the Social Historical Psychology, the subjective dimension of the dialectic process concern on inclusion/exclusion at work (with and without support) from people with intellectual deficiency as a way to reflect about professional education and supported work proposal. It is about to locate how the people with deficiency are situated historically, trying to understand which are the mediations and comprehend how is subjective lived the Cotes Law in the life of those people, and how this law work to orient the formation practices and job preparation that are offer to them. To do that, we will use the concepts of ethical-politic suffering, sense and meaning, social stigma, identity and preconception to analyze the living of looking for a job, and to became a worker with proper job preparation according to the conditions offers in the Cote, having as a background the social-historical condition unfavorable to inclusion to those people and the preparation project to the work that is given to them. The investigation method is based on Vygotsky s work that consider action, work and affect as in dissociable units of subjectivity, with the support of Spinoza philosophy and Marx s theory of society. The results pointed out a lag between juridical and social recognize, through the absence of social stigma, by preconception, by identity models presupposed, abandon and loneness, social conditions lived with sad felling, such as fear, humiliation, angry compromising the action potency of those people. The sense of work is ambiguous: it is only way to get self-esteem and recognition, (moreover than acquire deeds), however it is also fountain of sad passions, especially the constant fear of making a mistake, which will cost their job. It clams for work preparation and affective support, which those people encounter in their labor professor that accomplish them for a while, and to whom they send letters, expressing their feelings and needs. It is pointed out the importance of ―supported employment‖, where the professional act as a mediator to the effective of cotes law, at the development of abilities and as a affective reference / Esta pesquisa visa analisar na perspectiva da psicologia sócio-histórica a dimensão subjetiva do processo dialético de inclusão/exclusão no trabalho (com e sem apoio) das pessoas com deficiência intelectual para refletir sobre a educação profissional e a proposta de Emprego Apoiado. Trata-se de situar historicamente as pessoas com deficiência, buscando entender quais são as mediações presentes e compreendermos como é vivida subjetivamente a Lei de Cotas na vida dessas pessoas para orientar as práticas de formação e preparação ao trabalho que lhes são oferecidas. Para tanto, recorre aos conceitos de sofrimento ético-político, sentido e significado, estima social, identidade e preconceito para analisar a vivencia da busca por um trabalho, e de se tornar trabalhador nas condições de trabalho oferecidas pela Cota, tendo como pano de fundo a condição sócio-histórica desfavorável à inclusão oferecidas a esses sujeitos e os projetos de preparação para o trabalho que lhes são oferecidos. O método de investigação utilizado está embasado na concepção vygotskiana que considera ação, trabalho e afeto como unidades indissociáveis da subjetividade, amparada na filosofia de Espinosa e na teoria marxista de sociedade. Os resultados obtidos atestam a defasagem entre reconhecimento jurídico e social, pela ausência de estima social, pelo preconceito, pelos modelos de identidade pressupostas, desamparo e solidão a que são relegados, condição social vivida como sentimentos tristes de medo, humilhação, raiva comprometendo a potência de ação desses sujeitos O sentido de trabalho é ambíguo: ele é a única possibilidade de estima e reconhecimento, mais do que a possibilidade de adquirir bens, mas é também fonte de paixões tristes, especialmente o medo constante de errar e, assim perder o emprego. Clamam por preparação ao trabalho e apoio afetivo que eles encontraram no preparador laboral que os acompanhou por um tempo, ao qual enviaram cartas expressando seus sentimentos e necessidades. Ressalta-se a importância do ―Emprego Apoiado‖, onde o profissional desempenha o papel de mediador do cumprimento efetivo da lei de cotas, no plano de desenvolvimento de habilidades e da referência afetiva

Made available in DSpace on 2016-04-27T18:47:33Z (GMT). No. of bitstreams: 1 Rosemeire Cristina Buava Rodrigo.pdf: 911993 bytes, checksum: ca79967e542a82a80299892473cdf241 (MD5) Previous issue date: 2009-05-19 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / On this qualitative origin research, was investigated the meaning of the occupation workshop with intellectual deficiency elderly, having as theoretician base some gerontology basic concepts, as aging, oldness and special education area. To participate on the interviews were invited eight intellectual deficiency elderly aged sixty or more, and the responsible professional of the workshop performed on Comunidade de Amparo Social Asilar, in São Bernardo do Campo. The selection rule was the permanence time, of at least one year of frequency in the workshop. Developed information of the activities performed by the people, elements about the procedure and interpersonal relationship registered in specific notebooks were also used. The performed review revealed that emotional social relationship was marked by the speech pointing the wish on continuity of new knowledge and the importance of the performed activities on workshop and on elderly life. The feeling of friendship and concern with the other, express the human conscience on contemporary plurality / Nesta pesquisa de origem qualitativa investigou-se o significado das oficinas de ocupação para idoso com deficiência intelectual, tendo como base teórica conceitos básicos da gerontologia como envelhecimento e velhice e da área da educação especial. Foram convidados a participar das entrevistas oito idosos com deficiência intelectual e de idade de sessenta anos ou mais e o profissional responsável pelas oficinas de ocupação realizadas na Comunidade de Amparo Social Asilar situada no município de São Bernardo do Campo. O critério para seleção foi o tempo de permanência, de no mínimo, um ano de freqüência nas oficinas. Foram utilizadas, também, informações evolutivas das atividades realizadas pelos sujeitos, dados sobre conduta e relacionamento interpessoal registradas em cadernos específicos. O estudo realizado revelou que as relações sociais e afetivas foram marcadas pelos discursos que apontam o desejo na continuidade de novos aprendizados e a importância das atividades realizadas nas oficinas na vida dos idosos. O sentimento de amizade e preocupação com o outro traduz a consciência humana na pluralidade contemporânea

Grâce aux progrès de la génétique moléculaire qui ont permis d’identifier de nouveaux gènes de déficience intellectuelle liée à l’X, il nous a été possible de travailler sur des groupes homogènes de malades présentant une mutation dans le même gène. Nous avons d’une part, pu mettre en évidence un dysfonctionnement du circuit cérébello-thalamo-préfrontal grâce à une étude en IRM morphométrique réalisée chez des patients ayant une mutation dans le gène Rab-GDI. D’autre part, nous avons identifié un phénotype tout à fait spécifique lié aux mutations du gène ARX, tant clinique que neuropsychologique, et cinématique, associant une atteinte très particulière de la motricité distale des membres supérieurs et du langage. La préhension des patients est pathognomonique, avec une préférence pour la pince pouce-majeur, une difficulté accrue pour l’utilisation du bord cubital de la main, et un trouble de la pronosupination. Sur le plan neuroanatomique, il existe une diminution de volume des noyaux gris centraux et des épaisseurs corticales des régions contrôlant la motricité, bien corrélées au paramètres de cinématique. Enfin, nous avons exploré les stratégies de raisonnement des patients déficients intellectuels atteints du syndrome de l’X fragile, d’une mutation du gène ARX ou de trisomie 21 en élaborant un paradigme de raisonnement visuel analogique issu des matrices de Raven. Nous en avons établi la trajectoire développementale. Les stratégies utilisées par les patients (étude en eyetracking) sont différentes de celles des contrôles y compris de même âge mental, avec un défaut d’inhibition majeur, encore plus franc chez les patients X fragiles que ceux porteurs de trisomie 21 / Thanks to progress in molecular genetics, that allowed identification of new genes responsible for X linked intellectual disability, we studied on homogeneous groups of patients presenting with a mutation in one or the other gene. In the first section, we showed dysfunction of cerebello-thalamo-prefrontal networks, thanks to morphological MRI study performed on patients with a mutation in the Rab-GDI gene. In the second section, we highlighted a very specific phenotype related to ARX gene mutations, clinically, neuropsychologically, and kinematically, with a very peculiar impairment of upper limbs distal motricity, and language disorder. Patients hand-grip is pathognomonic, with a preference for the middle finger instead of the index for the grip of object, major impairment of fourth finger use, and lack of pronation movements. Neuroimaging study showed decreased volume of basal ganglia, and cortical thickness of motor regions, well correlated to kinematic parameters. In the third section, we explored reasoning strategies in three groups of patients with intellectual deficiency: fragile X, ARX mutated and Down syndrome patients and controls (both chronological and mental age-matched subjects). We notably elaborated a visual analogical reasoning paradigm, inspired from Raven’s matrices. We established a developmental trajectory of this paradigm. The strategy used by patients (eyetracking study) was different from the one used by controls, with a huge lack of inhibition, even greater for fragile X patients than for Down syndrome patients

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