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Citocinas pr? inflamat?rias, eixo hipot?lamo-hip?fiseadrenal e papel do BDNFna media??o da neurog?nese hipocampal no infarto do mioc?rdio em ratos / Proinflammatory cytokines, hypothalamic-pituitaryadrenal axis and role of BDNFin mediating hippocampal neurogenesis in myocardial infarction in ratsC?RTES, Rafael Sonoda 29 July 2016 (has links)
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Previous issue date: 2016-07-29 / CAPES / Myocardial infarction (MI) is the most prevalent nowadays syndrome. Similarly impressive, depression has caused many damages to health and the global economy. Epidemiologically, these different clinical conditions have a bidirectional relationship. Several studies in rats, in recent years, associated the emergence of analog signals depression post pathophysiological IM changes, among which the activation of pro-inflammatory factors and the activation of the hypothalamic-pituitary-adrenal endocrine axis (HPA). The objective of this study was: to study, in different rat groups, a short-term protocol, four days and a long, twenty-five days, the above features, besides elucidating the involvement of brain-derived neurotrophic factor (BDNF ) and hippocampal neurogenesis in the onset of depression induced experimental IM by ki-67 protein, cell proliferation marker. For this purpose, male Wistar rats (200-250 g) were subjected to IM through ligation of the left coronary artery and underwent preference for sucrose test and the open field test. They were measured: cardiac TNF-?, plasma and hypothalamic concentrations of TNF-? and IL-1?. In endocrine handle, plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone and hypothalamic levels of corticotropin releasing hormone (CRH). Finally, we measured plasma concentrations of BDNF to the association with the neurogenesis of the hippocampus, an important region in the pathophysiology of depression. In the long protocol, infarcted animals showed similar signs of depression compared to those operated fake animals. Concomitantly, showed elevated levels of TNF-? and IL-1?, CRH, ACTH and corticosterone plasma levels and reduced BDNF, suggesting decreased proliferation of granule cells in the hippocampus and hence the emergence of depression in response to MI. Although further studies are required, it is believed that
this study has translational impact serving experimental basis for the development of more effective future pharmacologic strategies to better quality and life expectancy of patients with myocardial infarction. / O infarto do mioc?rdio (IM) ? a s?ndrome de maior preval?ncia nos dias atuais. Semelhantemente impactante, a depress?o tem causado diversos preju?zos ? sa?de e a economia mundial. Epidemiologicamente, essas diferentes condi??es cl?nicas possuem uma rela??o bidirecional. Diversos estudos em ratos, nos ?ltimos anos, associam o surgimento de sinais an?logos a depress?o a altera??es fisiopatol?gicas p?s IM, dentre
as quais a ativa??o de fatores pr?-inflamat?rios e a hiperativa??o do eixo end?crino hipot?lamo-hip?fise-adrenal (HPA). O objetivo deste trabalho foi: estudar, em grupos distintos de ratos, num protocolo a curto prazo, de quatro dias e num longo, de vinte e cinco dias, as caracter?sticas supracitadas, al?m de elucidar a participa??o do fator neurotr?fico derivado do c?rebro (BDNF) e da neurog?nese hipocampal no surgimento da depress?o induzida por IM experimental, atrav?s da prote?na ki-67, marcador de prolifera??o celular. Para tanto, ratos Wistar machos (200-250g) foram submetidos ao
IM atrav?s da ligadura da art?ria coron?ria esquerda e submetidos ao teste de prefer?ncia pela sacarose, teste do nado for?ado e ao teste do campo aberto. Foram mensurados: os n?veis card?acos de TNF-? e as concentra??es plasm?ticas e hipotal?micas de TNF-? e IL-1?. Na al?a end?crina, as concentra??es plasm?ticas de horm?nio adrenocorticotr?fico (ACTH) e de corticosterona e os n?veis hipotal?micos de horm?nio liberador de corticotrofina (CRH). Por fim, foi mensurada as concentra??es plasm?ticas de BDNF para a associa??o com a neurog?nese do hipocampo, regi?o importante na fisiopatologia da depress?o. No protocolo longo, os animais infartados apresentaram sinais an?logos a depress?o em compara??o aos animais falso operados. Concomitantemente, apresentaram n?veis elevados de TNF-? e IL-1?, de CRH, ACTH e corticosterona e concentra??es plasm?ticas diminu?das de BDNF, sugerindo diminui??o da prolifera??o de c?lulas granulares no hipocampo e, consequentemente, o surgimento da depress?o em resposta ao IM. Embora sejam necess?rios mais estudos, acredita-se que este trabalho tenha impacto translacional, servindo de base experimental para o desenvolvimento de futuras estrat?gias farmacol?gicas mais eficazes para melhor qualidade e expectativa de vida de pacientes com infarto do mioc?rdio.
Palavras chave: Infarto, citocinas, depress?o
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An?lise imunoistoqu?mica da distribui??o de Serotonina, transportador de serotonina e receptores de serotonina no hipot?lamo do sagui (callithrix jacchus)Pontes, Andr? Luiz Bezerra de 11 April 2011 (has links)
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Previous issue date: 2011-04-11 / The hypothalamus is a diencephalic portion located around the third ventricle below the
hypothalamic sulcus, limited by the optic chiasm, and by the mammillary bodies, acting as
a center that integrates behavioral and homeostatic functions. Serotonin is a
neurotransmitter produced in limited sites in the midbrain and brain stem, but is distributed
throughout the central nervous system and has many functions, acting through specific
receptors that are also distributed throughout the nervous system. Using
immunohistochemical techniques, the aim of this study was to delineate the hypothalamic
nuclei of the marmoset (Callithrix jacchus) and study the distribution of serotonin
transporter and serotonin receptors in the hypothalamus of this species. We used the Nissl
method to determine the cytoarchitecture of the hypothalamic nuclei, and
immunohistochemistry to reveal the presence of NeuN as a method to determine the
contours of the hypothalamic nuclei. As a result, we found serotonin containing fibers and
terminals throughout the rostrocaudal extent of the hypothalamus, more concentrated in
some nuclei, and even absent in some. Like serotonin, serotonin transporter was observed
between pre-optic area and tuberal region of the hypothalamus, in densities and
distribution similar to serotonin. The 5-HT1A and 5-HT1B receptors were found with minor
differences among itselves regarding the disposition and intensity of staining. / O hipot?lamo ? uma por??o diencef?lica localizada ao redor do terceiro ventr?culo, abaixo
do sulco hipotal?mico, ventralmente vemos seu limite anterior feito pelo quiasma ?ptico e
posterior pelos corpos mamilares. Atuando como centro que integra fun??es homeost?ticas
e comportamentais. A serotonina ? um neurotransmissor produzido em s?tios restritos ao
mesenc?falo e tronco encef?lico, mas que ? distribu?do por todo o sistema nervoso central
e tem in?meras fun??es, atuando atrav?s de receptores espec?ficos que tamb?m est?o
distribu?dos por todo o sistema nervoso. Utilizando t?cnicas imunoistoqu?micas o objetivo
desse trabalho foi delimitar os n?cleos hipotal?micos do sagui (Callithrix jacchus), bem
como estudar a distribui??o de serotonina, transportador e receptores de serotonina no
hipot?lamo dessa esp?cie. Utilizamos o m?todo de nissl para determinar a citoarquitetura
dos n?cleos hipotal?micos, e a imunoistoqu?mica para revelar a presen?a de NeuN como
m?todo auxiliar para determinar os contornos dos n?cleos hipotal?micos. Como resultados,
encontramos fibras e terminais contendo serotonina por toda a extens?o rostro-caudal do
hipot?lamo, sendo mais concentrados em alguns n?cleos, e at? mesmo ausente em alguns;
assim como a serotonina, o transportador de serotonina foi observado entre a ?rea pr?
?ptica e a regi?o tuberal do hipot?lamo, com densidades e distribui??o semelhantes ?s da
serotonina. Os receptores 5-HT1A e 5-HT1B foram encontrados com diferen?as m?nimas,
entre si, quanto a disposi??o e intensidade de marca??o.
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O efeito da inje??o intracerebroventricular de neuropept?deo S na express?o de Fos em n?cleos dos circuitos de medo em camundongo SwissSilva, Fladjany Emanuelly Faustino da 05 August 2016 (has links)
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Previous issue date: 2016-08-05 / O medo e a ansiedade s?o emo??es adaptativas caracterizadas por um conjunto de altera??es fisiol?gicas e comportamentais que ocorrem quando os indiv?duos se sentem amea?ados fisicamente e/ou psicologicamente. Apesar dos comportamentos de medo e ansiedade serem caracter?sticos, estudo das ?ltimas duas d?cadas t?m mostrado que diferentes fontes de medo podem ativar diferentes vias neurais e que h? diferen?as entre medo condicionado (aprendido) e medo incondicionado (inato). As vias do medo condicionado envolvem o c?rtex frontal medial e os n?cleos central e basolateral da am?gdala, enquanto o medo de predador (inato) envolve o n?cleo medial da am?gdala e n?cleos da zona medial do hipot?lamo. Sabe-se que as fun??es encef?licas s?o coordenadas por sistemas de neurotransmissores e seus receptores que s?o expressos nas mais diversas regi?es do sistema nervoso, exercendo diferentes fun??es. O Neuropept?deo S (NPS) ? um neurotransmissor cujo estudos em roedores mostra sua import?ncia como regulador de ansiedade e vig?lia, reduzindo a ansiedade, aumentando a vig?lia e o comportamento locomotor, sendo ent?o um ansiol?tico e estimulante, o que o torna um potencial alvo para estudos farmacol?gicos e cl?nicos. Neste trabalho realizamos a inje??o intracerebroventricular (icv) de NPS em camundongos e mapeamento da express?o de Fos (prote?na indicadora de atividade celular) em n?cleos envolvidos nas vias de medo condicionado e incondicionado. A an?lise dos nossos resultados mostraram que a administra??o icv de NPS promoveu uma express?o de Fos diferenciada nos n?cleos central e basolateral da am?gdala, indicando um papel no medo condicionado. / Fear and anxiety are emotions featured by a group of physiological and behavioral changes that occur when subjects feel threatened physically and/or psychologically. For the last two decades many studies have showed that different sources of fear are able to activate different neural pathways, where conditioned (learned) and unconditioned (innate) fear run over different trails. The conditioned fear involves the frontal medial cortex and the central and basolateral nuclei of the amygdala, when the fear of predator (unconditioned) involves nuclei of the medial hypothalamus. It is known that the brain functions are coordinated by neurotransmitter's systems and its receptors that are expressed in many different places around the brain, having different functions. The Neuropeptide S (NPS) is a neurotransmitter whose studies have showed its important role as an anxiety and awake regulator. NPS decreases anxiety and increases awakeness and locomotor behavior, been thus an anxiolytic and stimulating neurotransmitter, what makes it a potential target for pharmacological and clinical studies. In the present work we injected NPS icv in mice and looked for the Fos-expressing neurons in the nuclei of the conditioned and unconditioned pathways. The analysis of our results showed that the icv NPS promoted the increase in Fos expression in the central and basolateral amygdala, what indicates its role in the conditioned fear.
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