Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 5 uppsatser.

Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 138-142).

Thesis (Ph. D.)--Cornell University, May, 2008. / Vita. Includes bibliographical references (leaves 143-165).

Thesis (Ph. D.)--University of Washington, 2005. / Vita. Includes bibliographical references (leaves 56-68).

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-04-15T14:05:59Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação_AndersonFelipe_Versão Final.pdf: 4770513 bytes, checksum: bd8c869ddc087cfbf7bc953f303cf9e5 (MD5) / Made available in DSpace on 2016-04-15T14:05:59Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação_AndersonFelipe_Versão Final.pdf: 4770513 bytes, checksum: bd8c869ddc087cfbf7bc953f303cf9e5 (MD5) Previous issue date: 2015-08-21 / A desnutrição durante o período perinatal tem sido associada a aumento da compulsão alimentar, preferência por alimentos palatáveis e risco de desenvolvimento de obesidade na vida adulta. O apetite é controlado por vários sistemas fisiológicos, dentre os quais o sistema neural de recompensa. A dopamina é um conhecido neurotransmissor deste sistema, estando envolvida nas relações de prazer proporcionado por alimentos e drogas, agindo através da ligação em receptores neuronais, de duas classes: D1-like e D2-like. O objetivo deste trabalho foi avaliar a expressão dos receptores dopaminérgicos D1 no Núcleo Accumbens e estriado, áreas relacionadas ao comportamento alimentar, em ratas desnutridas. Dois grupos experimentais foram formados: grupo-controle (CF - fêmeas gestadas por mães normonutridas durante a gestação e lactação) e grupo-desnutrido (DF - fêmeas gestadas por mães que receberam dieta hipoprotéíca no período perinatal). Os animais passaram a receber dieta-padrão de laboratório após o desmame e tiveram o peso avaliado em diferentes momentos da vida. No 120º dia, foram sacrificadas e submetidas à perfusão, para retirada dos encéfalos. Após os cortes dos cérebros em micrótomo de congelamento, procedeu-se a Imunohistoquímica para contagem de neurônios marcados para DRD1. As imagens foram obtidas através de câmera acoplada ao microscópio óptico e a morfometria realizada no software livre ImageJ. Os dados estatísticos foram expressos em média±desvio-padrão, sendo analisados no software livre GraphPad Prism 5. Os animais desnutridos apresentaram menor peso em relação aos normonutridos desde o nascimento até o sacrifício. Não foi encontrada diferença significativa entre os grupos na expressão de DRD1 nas áreas cerebrais analisadas (Estriado: CF: 230,0 ± 86,40, n=4; DF: 225,50 ± 89,90, n=4; Núcleo Accumbens: CF: 109,80 ± 41,40, n=4; DF: 128,0 ± 49,50, n=5; test t de Student, p<0,05). Estes dados sugerem que a expressão dos receptores D1 está diretamente relacionada à quantidade de dopamina liberada na fenda sináptica, quantidade essa que é maior na apresentação de alimentos novos e palatáveis. / Malnutrition during the perinatal period has been linked to increased binge eating, preference for palatable foods and risk of obesity developing in adulthood. Appetite is controlled by several physiological systems, including the neural reward system. Dopamine is a neurotransmitter in this system and it is involved in relations of pleasure provided by foods and drugs, acting through its binding to neuronal receptors of two classes: D1-like and D2-like. The goal of this study was to evaluate the expression of dopamine D1 receptors in the striatum and Nucleus Accumbens, areas related to feeding behavior, in malnourished rats. Two experimental groups were formed: the control group (CF - rats coming from normonutridas mothers during pregnancy and lactation) and group-malnourished (DF - coming rats of mothers who received low protein diet during the perinatal period). The animals began to receive standard laboratory diet after weaning and had the weight assessed at different times of life. In 120 days, they were sacrificed and submitted to perfusion, to remove the brains. After the cuts of the brains in freezing microtome, it proceeded to Immunohistochemistry for counting neurons marked for DRD1. The images were obtained through camera coupled to an optical microscope and morphometry performed on the Free Software ImageJ. Statistical data were expressed as mean ± standard deviation and analyzed the free software GraphPad Prism 5. Malnourished animals showed lower weight compared to well-nourished from birth to the sacrifice. There was no significant difference between groups in the expression of DRD1 the analyzed brain areas (Striatum: CF: 230.0 ± 86.40, n = 4; DF: 225.50 ± 89.90, n = 4; Nucleus Accumbens: CF: 109.80 ± 41.40, n = 4; DF: 128.0 ± 49.50, n = 5; Student's t test, p <0.05). These data suggest that the expression of D1 receptors is directly related to the amount of dopamine released in the synaptic cleft, which amount is higher in presenting new and palatable food.

The extended striatum is a large, dopamine-innervated forebrain structure comprising the caudate-putamen, nucleus accumbens and olfactory tubercle (OT). The OT remains largely unexplored, despite its potentially important role in behaviour and dopamine (DA)-mediated reward. One method of studying function is examining "supersensitive" behavioural responses to DA agonists in animals after striatal DA loss. We examined whether D1 or D2 receptor supersensitivity occurs in the OT and neighbouring islands of Calleja (ICj), after unilateral 6-hydroxydopamine lesions of the medial forebrain bundle and medial OT (mOT). We also asked if the resulting DA receptor supersensitivity is anatomically heterogeneous. Our results showed D1-like receptor supersensitivity occurring in the OT with several DA agonists, and heterogeneously across the extended striatum. There is evidence of D2-like receptor supersensitivity in the ICj. Our focal mOT lesion failed to show DA receptor supersensitivity. Finally, there is little evidence for D2 supersensitivity as measured by [ 35S]GTPgammaS binding.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

No description available.

Estudos clínicos nos pacientes com epilepsia mostram a importância da neurotransmissão modulada pela dopamina na epilepsia. Múltiplos fatores genéticos predispõem à epilepsia e há evidências de uma relação direta entre a epilepsia e as variações nos genes que codificam proteínas envolvidas na neurotransmissão dopaminérgica. O objetivo do nosso estudo foi investigar se os polimorfismos da via dopaminérgica e o Val66Met do BDNF estavam associados à ocorrência de epilepsia do lobo temporal causada por esclerose hipocampal. Para este fim, avaliamos 119 pacientes com epilepsia do lobo temporal causada por esclerose hipocampal e 113 voluntários saudáveis. Os participantes foram genotipados para os polimorfismos do gene DAT (3\'UTR e Intron 8), receptores dopaminérgicos (DRD2 e DRD4), COMT, MAO e BDNF (Val66Met). Não houve diferença entre pacientes e controles para os polimorfismos relacionados ao DAT, Íntron 8 VNTR (p 0,395) e 3\'UTR VNTR (p 0,614) e para a análise dos haplótipos (3\'UTR e Intron 8) (p 0.205). Não houve diferença entre pacientes e controles para os polimorfismos dos receptores dopaminérgicos DRD2 rs1800497 (p 0.440), DRD4 rs1800955 (p 0.548) e DRD4 VNTR (p 0.318). Não observamos diferença entre pacientes e controles quanto aos polimorfismos COMT rs4680 (p 0.482) e MAOA_uVNTR (p 0.753), metabolizadores de DA. Não observamos diferença na distribuição genotípica do polimorfismo Val66Met (rs6265) do BDNF (p 0,636) e a distribuição alélica (p 0.471) no grupo de pacientes com epilepsia do lobo temporal causada por esclerose do hipocampo. Nossos achados demonstraram que os polimorfismos da via dopaminérgica e BDNF Val66Met analisados neste estudo não parecem estar associados à epilepsia de lobo temporal causada por esclerose de hipocampo / Clinical studies in patients with epilepsy showed the role of neurotransmission modulated by dopamine in epilepsy. Multiple genetic factors predispose to epilepsy; there is evidence for a direct relationship between epilepsy and variations in genes encoding proteins involved in dopaminergic neurotransmission. The aim of our study was to investigate if the polymorphism related to the dopaminergic pathway and BDNF polymorphism Val66Met were associated with the occurrence of temporal lobe epilepsy caused by hippocampal sclerosis. We assessed 119 patients with unequivocal temporal lobe epilepsy caused by hippocampal sclerosis and 113 healthy volunteers. Individuals were genotyped for DAT gene polymorphisms (3\'UTR and Intron 8), dopaminergic receptors (DRD2 and DRD4), COMT, MAO and BDNF. There was no difference between patients and controls considering the polymorphisms related to DAT, Intron 8 VNTR (p 0,395) and 3\'UTR VNTR (p 0.614) and for the analysis of haplotypes (3\'UTR and Intron 8) (p 0.205). There was no difference between patients and controls considering the dopaminergic receptor polymorphisms DRD2 rs1800497 (p 0.440), DRD4 rs1800955 (p 0.548) and DRD4 VNTR (p 0.318). We observed no difference between patients and controls regarding COMT polymorphisms rs4680 (p 0.482) and MAOA_uVNTR (p 0.753), of dopaminergic metabolizers. We did not observe difference in the genotypic distribution of BDNF Val66Met polymorphism (rs6265) (p 0.636) and in the allelic distribution (p 0.4711) in the group with temporal lobe epilepsy caused by hippocampal sclerosis. Our findings suggest that the polymorphisms of the dopaminergic pathway evaluated in this study and BDNF Val66Me do not appear to be associated with temporal lobe epilepsy caused by hippocampal sclerosis