The mechanism of weight gain due to treatment with olanzapine, a serotonin receptor antagonist, has not been fully understood. Weight gain and food intake are under the control of neuropeptides/hormones, POMC (proopiomelanocortin), CART (cocaine and amphetamine regulated transcript), AgRP (Agouti-related peptide) and NPY (neuropeptide Y) that are synthesized and secreted from the arcuate nucleus (ARC) of hypothalamus. In this study, the altereration of the ARC neuropeptide/hormone levels both in humans and rats were determined as one of the weight gain mechanism. To examine olanzapine&rsquo / s weight gain effects, male first attack psychotic patients (pre-treatment), were hospitalized and treated for 4 -weeks (post-treatment), (n = 22), and healthy control group (n = 26) were included to the study. Case-control association design was used to analyze the changes in body mass index (BMI), peripheral leptin and the ARC neuropeptides levels. In patients, after 4-weeks of the olanzapine treatment / BMI and the waist circumference were significantly increased with average weight gain of 4.33 kg. In pre-treatment group, NPY levels were significantly lower while &alpha / -MSH, the anorexigenic product of POMC levels were significantly higher vs. control. At post-treatment, both leptin and NPY levels were significantly increased but the CART levels did not change. To further understand the underlying mechanism of olanzapine induced weight gain, the drug was orally administrated to 10 healthy male Wistar rats to analyze both the hypotalamic gene expression and peripheral levels of those candidate neuropeptides. In rats food consumption was increased and hypotalamic mRNA levels of NPY, AgRP and POMC were decreased while CART levels did not show any alteration. Consistent with the expression data, circulating levels of NPY, AgRP and &alpha / -MSH decreased significantly but CART levels were also reduced unexpectedly. In conclusion, it may be presumed that the antagonistic effect of olanzapine on the ARC neurons might be the basis for a disregulation of the neurohormones secretion which may cause weight gain in the treated psychotic patients.

The involvement of corticotropin-releasing hormone (CRH) and neuropeptide Y (NPY) in the pathophysiology of anxiety and anxiety-related disorders is well established. The objective of this study is to explore the genetic variations in the CRH and NPY genes in a well-documented behavioral animal model, the vervet monkey (Chlorocebus aethiops sabaeus), in order to uncover a possible association between these polymorphisms and behavioral traits quantitatively extracted following analysis of social behavior and responses to novelty challenges. / The vervet CRH and NPY genes were amplified and sequenced; the priority was given to the regions expanding from -1kb upstream of the transcription initiation site (where most of the regulatory elements are found in both genes) through the second exon. / Polymorphism discovery analysis revealed the presence of 9 vervet CRH SNPs and 9 vervet NPY SNPs; the SNPs are relatively evenly distributed across the regions covered. An association between one intronic NPY SNP and "defensive aggression" was detected. / These results are coherent with other reports implicating NPY in defensive aggressive behavior, and support the notion that fear responses are fundamental behavioral traits for the dissection of anxiety.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 6 uppsatser.

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

Thèses (Ph.D.)--Université de Sherbrooke (Canada), 2002. / Titre de l'écran-titre (visionné le 20 juin 2006). Publié aussi en version papier.

Thesis (Ph.D.)--University of Alberta, 2009. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Centre for Neuroscience. Title from pdf file main screen (viewed on October 31, 2009). Includes bibliographical references.

Thesis (Ph.D.)--Georgetown University, 2008. / Includes bibliographical references.

abstract: Externalizing behaviors are pervasive, widespread, and disruptive across a multitude of settings and developmental contexts. While the conventional diathesis-stress model typically measures the disordered end of the spectrum, studies that span the range of behavior, from externalizing to competence behaviors, are necessary to see the full picture. To that end, this study examined the additive and nonadditive relations of a dimension of parenting (ranging from warm to rejecting), and variants in dopamine, vasopressin, and neuropeptide-y receptor genes on externalizing/competence in a large sample of predominantly Caucasian twin children in toddlerhood, middle childhood, and early adolescence. Variants within each gene were hypothesized to increase biological susceptibility to both negative and positive environments. Consistent with prediction, warmth related to lower externalizing/higher competence at all ages. Earlier levels of externalizing/competence washed out the effect of parental warmth on future externalizing/competence with the exception of father warmth in toddlerhood marginally predicting change in externalizing/competence from toddlerhood to middle childhood. Warmth was a significant moderator of the heritability of behavior in middle childhood and early adolescence such that behavior was less heritable (mother report) and more heritable (father report) in low warmth environments. Interactions with warmth and the dopamine and vasopressin genes in middle childhood and early adolescence emphasize the moderational role gene variants play in relations between the rearing environment and child behavior. For dopamine, the long variant related to increased sensitivity to parent warmth such that the children displayed more externalizing behaviors when exposed to rejection but they also displayed more competence behaviors when exposed to high warmth. Vasopressin moderation was only present under conditions of parental warmth, not rejection. Interactions with neuropeptide-y and warmth were not significant. The picture that emerges is one of gene-environment interplay, wherein the influence of both parenting and child genotype each depend on the level of the other. As genetic research moves forward, gene variants previously implicated as conferring risk for disorder should be reexamined in conjunction with salient aspects of the environment on the full range of the behavioral outcome of interest. / Dissertation/Thesis / Ph.D. Psychology 2011

A elucidação dos mecanismos moleculares pelos quais tratamentos hormonais alteram o início da puberdade é de fundamental importância para o desenvolvimento de estratégias que reduzam a idade ao primeiro parto, e consequentemente a taxa de desfrute do rebanho Nelore. Foram investigados os efeitos do uso de dispositivos de progesterona, e do estradiol endógeno, sobre mecanismos moleculares controlando a obtenção da puberdade de novilhas Nelore peripúberes. Especificamente, como as diferenças na expressão de genes relativos à reprodução em duas áreas do hipotálamo. Trinta e cinco novilhas Nelores não púberes, e com idade entre 13 e 14 meses, foram divididas em quatro tratamentos experimentais (nove ou oito por tratamento): dispositivo de P4 sem estradiol (SP); dispositivo de P4 com estradiol (PE); sem dispositivo de P4 e sem estradiol (SS); e sem dispositivo de P4 e com estradiol (SE). As novilhas foram alimentadas no cocho pós desmame até atingirem 295 ± 11 kg, com fornecimento de água à vontade. Ao término do tratamento hormonal as novilhas foram abatidas e as porções de hipotálamo colhidas para processamento e armazenagem a -80 ºC. O RNA total do tecido hipotalâmico foi extraído, tratado com DNAse I e submetido à síntese de cDNA para estudo da expressão gênica por PCR em tempo real (qRT-PCR). Foram formados pools de RNA para a realização de um estudo abrangente da administração de progesterona e do efeito do estradiol endógeno e das diferenças entre áreas do hipotálamo, realizado por sequenciamento de nova geração (RNA-Seq), de forma a identificar possíveis genes candidatos no hipotálamo. Foram encontrados genes diferencialmente expressos alterados pelos tratamentos e entre as áreas do hipotálamo relativos à obtenção da puberdade. / The understanding of the molecular mechanisms by which nutrition, genetics and hormonal treatments affect the beginning of puberty is of great importance for developing strategies aiming to reduce the age at first calving, and therefore increase the slaughter rate in Nellore cattle. The effects of progesterone device and of endogenous estradiol on the molecular mechanisms controlling the attainment of puberty in Nellore heifers were investigated. Specifically, the molecular pathways of progesterone and estradiol were studied in the hypothalamus. Thirty five non-pubertal heifers, between 13 and 14 months of age, were divided into four treatment (nine or eight per treatment): P4 device without estradiol (SP), P4 device with estradiol (PE), without P4 device and without estradiol (SS), and without P4 device and with estradiol (SE). The heifers were fed after weaning until reach 295 ± 11 Kg, with water access. At the end of the hormonal treatments all heifers were slaughtered and the hypothalamus areas were harvested, processed and then also stored at -80°C. Total RNA of hypothalamus were extracted, treated with DNase I and submitted to cDNA synthesis for gene expression quantification by real time PCR (qRT-PCR). RNA samples were pooling to realize a comprehensive study of the effects of progesterone administration and endogenous estrogen on attainment of puberty by next-generation sequencing (RNA-Seq), in order to identify possible candidate genes in the hypothalamus. Genes diffentially expressed between hypothalamic areas and affected by treatments were found.