Thesis (M.A.)--University of Delaware, 2008. / Principal faculty advisor: Jeffrey B. Rosen, Dept. of Psychology. Includes bibliographical references.

Thesis (M. Phil.)--University of Hong Kong, 1995. / Includes bibliographical references (leaf 84-110).

Thesis (M. Phil.)--University of Hong Kong, 1999. / Includes bibliographical references (leaves 99-[110]).

Zugl.: Leipzig, Univ., Diss., 2009

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2010.

Thesis (M.Phil.)--University of Hong Kong, 1999. / Includes bibliographical references (leaves 99-[110]) Also available in print.

Thesis (Ph. D.)--University of Texas at Austin, 2008. / Vita. Includes bibliographical references.

Important physiological changes occur during lactation to allow for nourishment of the offspring. Specific neuronal groups within the arcuate nucleus of the hypothalamus influence prolactin (PRL) secretion, metabolism and fertility during lactation. Our overall goal was to identify gene expression changes in the arcuate nucleus during lactation and examine the roles of PRL and ovarian hormones in regulating expression of select genes. We evaluated transcriptome changes in the arcuate nucleus during lactation using RNA-sequencing. Thirty-seven differentially expressed genes, including neuropeptides, signaling molecules, receptors and enzymes, were identified between suckled and pup-deprived groups. Selected genes were evaluated by qRT-PCR in ovary-intact and ovariectomized lactating models, which included non-lactating, suckled and 24hr pup-deprived lactating groups. The mRNA expression of tyrosine hydroxylase (Th), kisspeptin (Kiss1), and neurokinin B (Tac3) was decreased, whereas mRNA expression of proenkephalin (Penk), parathyroid hormone 2 receptor (Pth2r), insulin-like growth factor binding protein 3 (Igfbp3), membrane progesterone receptor beta (Paqr8), suppressor of cytokine signaling 2 (Socs2) and cytokine-inducible SH2 domain-containing protein (Cish) was increased in suckled lactating rats. In 24hr pup-deprived dams, mRNA expression of Pth2r, Igfbp3, Paqr8, Socs2 and Cish was decreased and Th was increased, as compared to suckled rats. The mRNA expression of Kiss1 and Tac3 was increased and Penk was decreased after 72hr, but not 24hr, pup deprivation suggesting gene expression of these neuropeptides is slow to return to non-lactating levels after removing the suckling stimulus. Tyrosine hydroxylase (TH) protein and enkephalin (ENK) peptide expression was examined by immunohistochemistry. Lactating rats had increased ENK in the median eminence and decreased TH in the median eminence and arcuate nucleus as compared to virgin ovariectomized rats. ENK co-localization with TH in the arcuate nucleus was more predominant in lactating rats. Penk, Igfbp3, Pth2r, Cish, and Socs2 mRNA expression was decreased after 72hr bromocriptine treatment in suckled rats, suggesting that these genes are PRL-regulated. In contrast, gene expression of Th, Tac3 and Kiss1 were increased and Paqr8 was decreased with 72hr pup-deprivation, but expression of these genes, were not altered with bromocriptine treatment, indicating that these genes are regulated by a non-PRL component of the suckling stimulus. The mRNA expression of Kiss1, Socs2 and Igfbp3 was increased and Penk was decreased in ovariectomized as compared to ovary intact lactating rats, suggesting that ovarian hormones influence the expression of these genes during lactation. Our data show gene expression changes in the arcuate nucleus that may contribute to increased PRL secretion (Th, Penk and Pth2r), decreased PRL receptor signaling (Cis and Socs2), reduced fertility (Kiss1 and Tac3), increased metabolism (Igfbp3) and support a role for progesterone membrane actions (Paqr8). The expression of some genes appeared to be selectively regulated by ovarian hormone input and/or PRL feedback.

Made available in DSpace on 2015-10-06T13:03:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-02-26. Added 1 bitstream(s) on 2015-10-06T13:18:50Z : No. of bitstreams: 1 000847714_20170226.pdf: 398877 bytes, checksum: 1c5a7cb0d627e81c66d8680f36c5dc89 (MD5) Bitstreams deleted on 2017-03-03T11:01:28Z: 000847714_20170226.pdf,. Added 1 bitstream(s) on 2017-03-03T11:02:38Z : No. of bitstreams: 1 000847714.pdf: 13242420 bytes, checksum: 9bd279660ca7b927284ab05d7d343cb8 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O hormônio concentrador de melanina (MCH) do rato é um nonadecapeptídeo presente em neurônios localizados, principalmente, na área hipotalâmica lateral (LHA) que se projetam para diversas regiões do neuro-eixo. O MCH está envolvido em diversas funções, tais como: reprodução, certos aspectos do comportamento motivado, atividade locomotora, percepção sensorial, controle de temperatura, memória, aprendizagem, ansiedade, ciclo sono-vigília e comportamento alimentar. Nesse, o MCH atua como neuropeptídeo orexígeno. Durante o envelhecimento, ocorre a diminuição no consumo de energia associada à idade. Nesse trabalho, analisamos em diferentes faixas etárias, as variações da expressão do MCH na área hipotalâmica lateral, empregando métodos esterológicos (para estimar o número de neurônios MCH-ir, área, volume e densidade neuronal), reconstrução tridimensional (para estudo da distribuição dos neurônios MCH-ir) e densitometria óptica de tecido hibridizado para reconhecimento do RNAm do ppMCH (para mensuração da área hibridizada, densidade óptica média e densidade óptica integrada [DOI]) na LHA e em suas regiões. Foram utilizados 35 ratos Sprague-Dawley machos, divididos em 7 grupos experimentais de diferentes idades: 14 (lactente), 28 (pré-púbere), 50 (púbere), 90 (adulto jovem), 210 (adulto maduro), 540 (adulto senescente) e 750 (adulto senil) dias pós-natais. Os animais foram submetidos à perfusão transcardíaca, seus encéfalos coletados e processados para análise da expressão do MCH na área hipotalâmica lateral, segundo protocolos de imuno-histoquímica e hibridização in situ. A LHA apresentou um aumento significativo no número de neurônios apenas entre os grupos de 14 e 28 dias e sua área e volume foram significativamente menores apenas no grupo de 14 dias em relação a todos os grupos, com exceção do grupo de 750 dias. No entanto, com relação a densidade neuronal não foram observadas... / The Melanin-Concentrating Hormone (MCH) is a nonadecapeptide located mainly in neurons in the lateral hypothalamic area (LHA), which innervate several regions of neuraxis. MCH is involved in many functions as reproduction, aspects of motived behaviors, motor activity, sensorial information, temperature control, memory, learning, anxiety, sleep-wake cycle and feeding behavior in which the MCH plays an orexigenic role. The energy consumption in aging is reduced as well as, the expression of MCH presents alterations associated with age. Therefore, we analyzed the variations in the expression of MCH at different ages in the lateral hypothalamic area, using stereology (to estimate the number of MCH-ir neurons, area, volume and neuronal density), 3D reconstruction (to study the distribution of MCH-ir neurons) and optical density after in situ hybridization protocol for ppMCH RNAm (to measure the hibridizated area, the mean optical density and the integrated optical density [IOD]) in the LHA and its three regions. In this study, 35 animals were divided in 7 experimental groups of 14 (neonate), 28 (prepubescent), 50 (pubescent), 90 (young adult), 210 (middle aged adult), 540 (senescent adult) and 750 (elderly adult) postnatal days. All the animals were perfused via the ascending aorta, the brains were collected and processed by immunohistochemistry and in situ hybridization protocols to analyze the expression of MCH in the lateral hypothalamic area. LHA neurons number increased only between groups of 14 and 28 days, and its area and volume significantly smaller in 14-days group when in respect to all other groups but the 750-days one. However, there weren't differences in neuronal density among groups. MCH-ir neurons distribution in LHA and contiguous regions was similar among all groups as well. Hypothalamic MCH-ir neurons has shown uniform rates in and out of LHA, but after analyzing its distribution in mamillary, tuberal and anterior ... / FAPESP: 2013/08618-3

Cerca de metade dos brasileiros adultos apresentam obesidade ou sobrepeso, sendo o excesso de ganho de peso durante a gestação um dos mais importantes fatores de risco para o desenvolvimento da obesidade em mulheres. Além do ganho de peso excessivo durante a gravidez, o diabetes gestacional é outro problema metabólico enfrentado frequentemente por gestantes. No presente trabalho demonstramos que a expressão de SOCS3 em células que expressam o receptor de leptina (LepR) é essencial para causar plenamente a hiperfagia decorrente da gestação e lactação, que consequentemente, reduz o ganho de peso e o acúmulo de gordura durante estes períodos, garantindo menor retenção do peso pós-parto. Finalmente, a deleção do gene SOCS3 em células que expressam o LepR melhorou significantemente a homeostase glicêmica durante a gestação protegendo as fêmeas contra o desenvolvimento do diabetes gestacional. / About half of brazilian adults are obese or overweight, and excess weight gain during pregnancy among the most important risk factors for the development of obesity in women. Besides the excessive weight gain during pregnancy, gestational diabetes is another metabolic problem often faced by pregnant women. The present work we demonstrated that the expression of SOCS3 in LepR expressing cells has proved essential to fully cause hyperphagia due to pregnancy and lactation that, as a consequence, reduces weight gain and fat accumulation during these periods, ensuring a lower weight retention postpartum. Finally, the conditional deletion of SOCS3 significantly improves glucose homeostasis during pregnant females protecting against the development of gestational diabetes.