Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-03-31T23:30:54Z No. of bitstreams: 1 FernandaCarvalhoCagni_DISSERT.pdf: 1786366 bytes, checksum: c9744d9e47a1b28a2acd8f572b07d5da (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-04-05T20:01:37Z (GMT) No. of bitstreams: 1 FernandaCarvalhoCagni_DISSERT.pdf: 1786366 bytes, checksum: c9744d9e47a1b28a2acd8f572b07d5da (MD5) / Made available in DSpace on 2016-04-05T20:01:37Z (GMT). No. of bitstreams: 1 FernandaCarvalhoCagni_DISSERT.pdf: 1786366 bytes, checksum: c9744d9e47a1b28a2acd8f572b07d5da (MD5) Previous issue date: 2015-05-12 / As doen?as neurodegenerativas s?o objeto frequente de estudo devido ao n?mero crescente de casos associados ao processo de envelhecimento populacional e pelo impacto que causam na qualidade de vida dos indiv?duos. A doen?a de Parkinson (DP) ? a segunda doen?a neurodegenerativa mais frequente. Apesar da sua etiologia ainda n?o ser completamente conhecida, sabe-se que a mesma ? causada por fatores ambientais e gen?ticos. Assim, a investiga??o dos fatores etiol?gicos e os mecanismos respons?veis pelas altera??es que levam a DP podem contribuir para o seu diagn?stico e preven??o. Uma poss?vel associa??o entre DP e o polimorfismo comum do Fator Neurotr?fico Derivado do C?rebro (BDNF) G196A (Val66Met) tem sido sugerido por diferentes estudos com resultados contrastantes. Por esse motivo, o objetivo deste estudo ? verificar se o polimorfismo BDNF Val66Met confere susceptibilidade a DP em uma amostra de pacientes brasileiros e se isso implica em quaisquer altera??es no n?vel de BDNF em sangue total e na manifesta??o de sintomas. A amostra foi constitu?da de pacientes acompanhados pelo servi?o de neurologia do Hospital Universit?rio Onofre Lopes (HUOL) e controles saud?veis (CTRL). Os aspectos motores da DP foram avaliados pela Escala de Hoehn e Yahr (HY), Unified Parkinson?s Disease Rating Scale (UPDRS) e Escala de Atividades Di?rias de Schwab e England (SE). Para a avalia??o dos aspectos n?o-motores foram utilizados os instrumentos: Bateria de Avalia??o Frontal (BAF), Mini Exame do Estado Mental (MEEM), Invent?rio de Depress?o de Beck (IDB) e o Invent?rio de Ansiedade de Beck (IAB). Amostras de sangue foram coletadas para a genotipagem do polimorfismo Val66Met e mensura??o da concentra??o de BDNF em sangue total. Como esperado, os pacientes com DP apresentaram pior desempenho na avalia??o motora, cognitiva e emocional. A distribui??o dos alelos entre os grupos n?o foi significativamente diferente, por?m o gen?tipo A/G foi associado significativamente como protetor para a DP. O gen?tipo G/G, por sua vez, foi associado significativamente com o desenvolvimento de depress?o e ansiedade em pacientes com DP. No entanto, as concentra??es de BDNF n?o foram diferentes entre os gen?tipos ou grupos. Este ? o primeiro estudo de associa??o gen?tica desse polimorfismo com a DP no Brasil e o primeiro que associou o heterozigoto A/G com prote??o contra a DP. / Neurodegenerative diseases are frequently studied due to the increasing number of cases associated with the populational ageing and to the impact on the conditions on the quality of life. Parkinson?s disease (DP) is the second most frequent neurodegenerative disease. Despite the fact that its etiology is not completely understood, it is known that DP is caused by environmental and genetic factors. Thus, the investigation of etiologic factors and mechanisms responsible for the changes that lead to DP may help early diagnostic and prevention. A possible association between DP and the common polymorphism of Brain Derived Neurotrophic Factor (BDNF) G196A (Val66Met) has been suggested by different studies with contrasting results. For this reason, the aim of this study is to investigate if the BDNF Val66Met polymorphism is related to susceptibility to DP in a cohort of Brazilian patients. Additionaly, we verify if the presence of the polymorphism implies in alterations in the BDNF whole blood concentrations, as well as variations in symptomatology. The sample comprised Brazilian patients accompanied by the neurology service of the Onofre Lopes University Hospital (HUOL) and healthy controls (CTRL). The motor aspects of DP were evaluated by Hoehn e Yahr Scale (HY), Unified Parkinson?s Disease Rating Scale (UPDRS) and Schwab & England Scale (SE). For the evaluation of non-motor symptoms were used the following instruments: Frontal Assessment Battery (BAF), Mini-Mental State Examination (MEEM), Beck Depression Inventory (IDB) and the Beck Anxiety Inventory (IAB). Blood samples were collected for BDNF Val66Met polymorphism genotyping and BDNF whole blood measurement. As expected, DP patients performed worse in motor, cognitive and emotional battery of questionnaires. Alleles distribution between DP and CTRL was not significantly different, but the A/G genotype was significantly associated with a protector factor for DP. In contrast, the G/G genotype was significantly associated with depression and anxiety development in DP patients. However, BDNF concentrations were not different between genotypes or groups. This is the first study of genetic association of this polymorphism with DP in Brazilian subjects and the first one that associate A/G genotype with protection against DP.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-01-03T19:56:08Z No. of bitstreams: 1 CinthyaMontenegroDeVasconcelosSilva_DISSERT.pdf: 1465896 bytes, checksum: 0fbac94f7a38a84105e55f2ee7340731 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-01-05T22:10:42Z (GMT) No. of bitstreams: 1 CinthyaMontenegroDeVasconcelosSilva_DISSERT.pdf: 1465896 bytes, checksum: 0fbac94f7a38a84105e55f2ee7340731 (MD5) / Made available in DSpace on 2017-01-05T22:10:42Z (GMT). No. of bitstreams: 1 CinthyaMontenegroDeVasconcelosSilva_DISSERT.pdf: 1465896 bytes, checksum: 0fbac94f7a38a84105e55f2ee7340731 (MD5) Previous issue date: 2016-05-13 / A doen?a de Parkinson (DP) ? uma desordem neurodegenerativa e progressiva com espectro cl?nico variado. Al?m dos sintomas motores cl?ssicos tamb?m podem surgir complica??es n?o-motoras, destacando-se a? problemas cognitivos, psiqui?tricos e auton?micos. Evid?ncias demonstram que tais sintomas n?o-motores frequentemente precedem o aparecimento dos sinais motores e s?o extremamente relevantes, dado o impacto negativo que causam na qualidade de vida dos indiv?duos. Os sintomas n?o-motores podem apresentar m?ltiplas causas, dentre as quais uma poss?vel disfun??o do sistema circadiano. Dessa forma, diversos processos fisiol?gicos influenciados pelo sistema de temporiza??o circadiano (STC), como o ciclo sono/vig?lia podem se mostrar alterados em pacientes acometidos pela DP. O STC ? respons?vel pela gera??o e manuten??o dos ritmos circadianos, que s?o oscila??es end?genas manifestadas pelos seres vivos em diversos processos fisiol?gicos e comportamentais, com per?odo em torno de 24 horas. Assim, ? fundamental a compreens?o dos efeitos da progress?o do processo patog?nico da DP sobre o perfil circadiano do ciclo sono/vig?lia e tamb?m de componentes do STC, em particular no n?cleo supraquiasm?tico (NSQ), o principal marcapasso do sistema. No presente estudo, ratos wistar jovens (6 meses) e de meia-idade (10 meses) foram submetidos a um modelo animal cr?nico de DP com administra??o de reserpina durante 20 dias. Ao longo do tratamento foram realizadas an?lises comportamentais do sono, bem como a avalia??o motora dos animais. Ap?s o fim do tratamento, foram realizadas an?lises imunoistoqu?micas no NSQ dos animais. Nossos resultados mostraram que o tratamento cr?nico com reserpina promoveu comprometimento motor progressivo tanto nos animais jovens quanto nos de meia-idade. Al?m disso, as an?lises comportamentais revelaram perturba??es no ciclo sono/vig?lia dos animais tratados em compara??o aos indiv?duos controle, incluindo avan?o na fase de sono e aumento na fragmenta??o do sono. As an?lises imunistoqu?micas n?o permitiram observar efeitos significativos do tratamento com reserpina sobre a composi??o neuroqu?mica do NSQ, contudo novos estudos s?o necess?rios para a avalia??o neuroqu?mica e morfom?trica desse importante marcapasso circadiano na DP. / Parkinson?s disease (PD) is a neurodegenerative and progressive disorder with varied clinical spectrum. In addition to the classic motor symptoms may also emerge non-motor complications, highlighting cognitive, psychiatric and autonomic problems. Evidence shows that such non-motor symptoms often precede the onset of motor signs and are extremely relevant given the negative impact they have on the quality of life of the individuals. Non-motor symptoms may present multiple causes, among which a possible dysfunction of the circadian system. Therefore, many physiological processes influenced by the circadian timing system (CTS) as the sleep / wake cycle can show alterations in PD patients. In this study we sought to evaluate the profile of sleep/wake behavior in a chronic model of PD in rats compared with possible neurochemical changes in the suprachiasmatic nucleus(SCN), the main pacemaker of the CTS. To this end, young (6 months) and middle-age (10 months) wistar rats were subjected to a treatment with repeated administration of reserpine (0.1 mg / kg) for 20 days. During treatment sleep behavioral analysis were performed as well as the motor assessment of the individuals. After the end of treatment, immunohistochemical analyzes were performed in the SCN of the animals. Our results showed that chronic treatment with reserpine promoted progressive motor impairment both in young as in middle-age animals. It is noticed significant losses from the 12th day of treatment. Furthermore, the behavioral analyzes revealed disturbances in sleep / wake cycle of the treated animals compared to control subjects, including advanced sleep phase and increased sleep fragmentation. Such changes were observed from the 6th day of treatment, prior to the onset of motor symptoms. The immunohistochemical analysis not allowed to observe significant effects of treatment with reserpine on the neurochemical composition of the SCN. Thus, our data support the observation that non-motor symptoms precede the onset of motor symptoms in PD and are extremely important for early clinical diagnosis of the disease.