Na realização do tratamento ortodôntico, é descrito que a dor ocorre imediatamente após a aplicação das forças ortodônticas e desaparece após alguns dias. Com relação às vias neurais envolvidas na mediação sensorial da movimentação ortodôntica (MO) poucos são os estudos que abordam esse tema, e nas últimas décadas achados consistentes demonstram o envolvimento do sistema trigeminal, bem como de suas áreas de projeção nessa mediação. Nesse contexto, achados demonstram que além de áreas do tronco encefálico, regiões da substância cinzenta periaquedutal, o núcleo espinhal do trigêmio, a área parabraquial e áreas límbicas apresentam aumento da imunorreatividade à proteína FOS (IR-FOS) 24hs após o início da movimentação dentária de molares de ratos. É possível que esta ativação límbica ocorra devido à liberação local de prostaglandinas. Assim, o presente trabalho avaliou temporalmente (3, 6, 24 e 48hs) a ativação do núcleo central da amígdala (CEA) e do hipotálamo lateral (HL) após MO. Em adição, verificamos se a pré-administração de diclofenaco de sódio (analgésico e antiinflamatório) ou de sulfato de morfina (analgésico de ação central) altera a IR-FOS após a aplicação de força para movimentação dentária de incisivos superiores de ratos, nas áreas analisadas. Nossos resultados mostram que a MO aumentou a IR-FOS no CEA e no HL após 3, 6 e 24hs. Após a MO por 48hs, a IR-FOS foi semelhante ao controle. A análise histológica do periodonto desses animais evidenciou processo ativo de remodelação óssea, sugerindo aposição de matriz colágena e a análise radiográfica demonstrou que a separação dos incisivos superiores dos animais ocorreu devido ao movimento ortodôntico e não ortopédico, já que não houve abertura da sutura palatina mediana. O pré-tratamento com sulfato de morfina (2mg/kg) inibiu a IR-FOS em ambas as áreas estudadas, sugerindo que a expressão de FOS após MO possa ser devido à transmissão da informação nociceptiva. Ainda, o pré-tratamento com diclofenaco de sódio (5mg/kg) reduziu a IR-FOS no CEA e no HL nos animais que receberam o aparelho ortodôntico por 6hs / In the accomplishment of the orthodontic treatment, it is described that the pain happens immediately after the application of orthodontic forces and disappears after few days. Regarding the neural pathways involved in the sensorial mediation of the orthodontic movement (OM) few are the studies that approach this theme, and in the last decades solid founds demonstrate the involvement of the trigeminal system as well as its projection areas in this mediation. In this context, discoveries demonstrate that besides brainstem areas, such as periaquedutal gray matter, trigeminal spinal nucleus, and parabrachial area, limbic areas can present increase in FOS immunorreactivity(IR-FOS) 24 hours after the beginning of the tooth movement of rat molars. It is possible that this limbic activation happens due to the local liberation of prostaglandins. In this way, this work evaluated the activation of the central amygdala (CEA) and the lateral hypothalamus (LH) after OM. In addition, we verified if the previous administration of sodium diclofenac (painkiller and anti-inflammatory) or of morphine sulfate (painkiller of central action) alters IR-FOS after the application of force for tooth movement of rat superior incisors, in the analyzed limbic areas. Our results show that the OM increased the IR-FOS in CEA and in HL after 3, 6 and 24hs. After the OM for 48hs, the IR-FOS was similar to the control. The histological periodontal analysis of those animals evidenced an active process of bone remodeling, suggesting the deposition of osteoid material and the radiographic analysis demonstrated that the separation of the superior incisors of the animals happened due to the orthodontic movement and not orthopedic movement, since the interpremaxillary suture was fused. The pre-treatment with morphine sulfate (2mg/kg) inhibited the IR-FOS in both studied areas, suggesting that the expression of FOS after OM can be due to the transmission of nociceptive information. In addition, pre-treatment with sodium diclofenac (5mg/kg) reduced IR-FOS in CEA and in HL in the animals that received the orthodontic apparel for 6hs.

Na realização do tratamento ortodôntico, é descrito que a dor ocorre imediatamente após a aplicação das forças ortodônticas e desaparece após alguns dias. Com relação às vias neurais envolvidas na mediação sensorial da movimentação ortodôntica (MO) poucos são os estudos que abordam esse tema, e nas últimas décadas achados consistentes demonstram o envolvimento do sistema trigeminal, bem como de suas áreas de projeção nessa mediação. Nesse contexto, achados demonstram que além de áreas do tronco encefálico, regiões da substância cinzenta periaquedutal, o núcleo espinhal do trigêmio, a área parabraquial e áreas límbicas apresentam aumento da imunorreatividade à proteína FOS (IR-FOS) 24hs após o início da movimentação dentária de molares de ratos. É possível que esta ativação límbica ocorra devido à liberação local de prostaglandinas. Assim, o presente trabalho avaliou temporalmente (3, 6, 24 e 48hs) a ativação do núcleo central da amígdala (CEA) e do hipotálamo lateral (HL) após MO. Em adição, verificamos se a pré-administração de diclofenaco de sódio (analgésico e antiinflamatório) ou de sulfato de morfina (analgésico de ação central) altera a IR-FOS após a aplicação de força para movimentação dentária de incisivos superiores de ratos, nas áreas analisadas. Nossos resultados mostram que a MO aumentou a IR-FOS no CEA e no HL após 3, 6 e 24hs. Após a MO por 48hs, a IR-FOS foi semelhante ao controle. A análise histológica do periodonto desses animais evidenciou processo ativo de remodelação óssea, sugerindo aposição de matriz colágena e a análise radiográfica demonstrou que a separação dos incisivos superiores dos animais ocorreu devido ao movimento ortodôntico e não ortopédico, já que não houve abertura da sutura palatina mediana. O pré-tratamento com sulfato de morfina (2mg/kg) inibiu a IR-FOS em ambas as áreas estudadas, sugerindo que a expressão de FOS após MO possa ser devido à transmissão da informação nociceptiva. Ainda, o pré-tratamento com diclofenaco de sódio (5mg/kg) reduziu a IR-FOS no CEA e no HL nos animais que receberam o aparelho ortodôntico por 6hs / In the accomplishment of the orthodontic treatment, it is described that the pain happens immediately after the application of orthodontic forces and disappears after few days. Regarding the neural pathways involved in the sensorial mediation of the orthodontic movement (OM) few are the studies that approach this theme, and in the last decades solid founds demonstrate the involvement of the trigeminal system as well as its projection areas in this mediation. In this context, discoveries demonstrate that besides brainstem areas, such as periaquedutal gray matter, trigeminal spinal nucleus, and parabrachial area, limbic areas can present increase in FOS immunorreactivity(IR-FOS) 24 hours after the beginning of the tooth movement of rat molars. It is possible that this limbic activation happens due to the local liberation of prostaglandins. In this way, this work evaluated the activation of the central amygdala (CEA) and the lateral hypothalamus (LH) after OM. In addition, we verified if the previous administration of sodium diclofenac (painkiller and anti-inflammatory) or of morphine sulfate (painkiller of central action) alters IR-FOS after the application of force for tooth movement of rat superior incisors, in the analyzed limbic areas. Our results show that the OM increased the IR-FOS in CEA and in HL after 3, 6 and 24hs. After the OM for 48hs, the IR-FOS was similar to the control. The histological periodontal analysis of those animals evidenced an active process of bone remodeling, suggesting the deposition of osteoid material and the radiographic analysis demonstrated that the separation of the superior incisors of the animals happened due to the orthodontic movement and not orthopedic movement, since the interpremaxillary suture was fused. The pre-treatment with morphine sulfate (2mg/kg) inhibited the IR-FOS in both studied areas, suggesting that the expression of FOS after OM can be due to the transmission of nociceptive information. In addition, pre-treatment with sodium diclofenac (5mg/kg) reduced IR-FOS in CEA and in HL in the animals that received the orthodontic apparel for 6hs.

Thesis advisor: Gorica Petrovich / Novel foods and novel environments both impact consumption, but their interaction is poorly understood, especially how this interaction varies across habituation and by sex. Prior studies found that placement in a novel context suppressed consumption of a novel food across habituation in a two-choice paradigm with familiar food, and there were neural correlates in the amygdala of consumption under novelty during the first exposure. The current study extended these findings using a paradigm with only a novel food. We placed adult male and female rats in a novel or familiar environment and measured their consumption of a novel, palatable food across four habituation sessions and a final test session. We collected brain tissue after the test session to measure Fos induction with immunohistochemistry during the final exposure to novelty. Fos induction was measured in the central nucleus of the amygdala and the nuclei of the basolateral complex. We found that placement in a novel context suppressed consumption of a novel food at every time point. During the test, Fos induction was elevated in groups tested in the novel context in the medial part of the central nucleus and all nuclei of the basolateral complex except the anterior part of the basolateral nucleus despite the test being the fifth exposure to the novel stimuli. Parts of the central nucleus and nuclei of the basolateral complex showed sex-specific elevations in Fos induction in females regardless of the testing context. Correlations of Fos induction across regions showed that novel context tested groups had similarly elevated Fos induction throughout the central nucleus and basolateral complex, unlike their familiar context tested counterparts. Females had more correlations of Fos induction than males regardless of testing context. These results demonstrated that habituation to eating a novel food is prolonged in a novel environment compared to a familiar environment. Notably, Fos induction remained high in the novel context groups after multiple exposures to novelty. These behavioral and neural findings demonstrate that unfamiliar environments remain salient throughout the process of habituation. / Thesis (MA) — Boston College, 2023. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Psychology and Neuroscience.

La neurotensine (NT) est un neuropeptide de 13 acides aminés qui fut isolé au début des années 70. Suite à sa découverte, il a été démontré qu'il était localisé autant au niveau central que périphérique et que ses rôles étaient étroitement liés à sa localisation. Pour exercer ses nombreux effets, incluant l'induction d'une analgésie naloxone-indépendante, la NT interagit avec 3 sous-types de récepteurs soit NTS1, NTS2 et NTS3. Jusqu'à maintenant, l'implication du récepteur NTS1 dans l'analgésie induite par la NT a été démontrée uniquement dans des modèles de douleur aiguë. Nous avons donc décidé de caractériser le rôle du récepteur NTS1 1 dans un modèle de douleur tonique, le test à la formaline. Ce test est composé de deux phases actives soit la phase I dite aiguë et la phase II dite inflammatoire. Ces deux phases sont entrecoupées par une interphase où il y a une inhibition active des comportements douloureux. Le test à la formaline permet une analyse rapide et efficace du potentiel analgésique de composés qui pourront être testés ultérieurement en douleur chronique. Lors des études comportementales, nous avons observé que la NT induit un effet analgésiant dose-indépendant. Les comportements douloureux ont diminué jusqu'à 23% dans la phase inflammatoire et ce avec les doses les plus élevées de NT. Pour déterminer plus précisément l'implication du récepteur NTS1 dans l'analgésie induite par la NT, nous avons évalué l'effet de deux agonistes de ce récepteur soit le PD149163 et le NT69L. Ces deux agonistes ont démontré un effet analgésiant plus important que celui de la NT. Avec le PD149163 et le NT69L, l'intensité douloureuse a diminué de façon dose-dépendante jusqu'à 61 et 48% respectivement dans la phase inflammatoire et ce avec les doses les plus élevées utilisées. Pour confirmer les résultats obtenus avec les agonistes du récepteurs NTS1, nous avons co-administré chaque agoniste avec un antagoniste du récepteur NTS1 1, le SR48692. La combinaison du PD149163 et du SR48692 a induit un retour significatif de la douleur chez les animaux traités tandis que la combinaison du NT69L et du SR48692 a renversé partiellement l'effet du NT69L seul. En sachant que le NT69L lie les récepteurs NTS1 1 et NTS2, ces résultats indiquent donc que les récepteurs NTS1 et NTS2 sont à considérer dans l'analgésie observée lors du test à la formaline. Afin de déterminer l'impact cellulaire des agonistes NTS1 lors du test à la formaline, nous avons révélé l'activité neuronale spinale via l'expression de la protéine Fos par la technique d'immunohistochimie. Du côté ipsilatéral à l'injection de formaline, une diminution significative de l'expression de la protéine Fos a été observée avec la NT, le PD149163 et le NT69L au niveau des lamina III-IV et V-VI. Les agonistes du récepteur NTS1 ont aussi eu un effet diminutif dans les lamina I-II en plus d'être les seuls à avoir atténué l'expression de la protéine Fos au niveau des lamina III-IV et VI du côté controlatéral. L'activité neuronale spinale corrèle bien avec les résultats comportementaux obtenus avec les différents composés étudiés. Cette étude nous suggère donc que les agonistes du récepteur NTS1 pourraient représenter une nouvelle voie de composés analgésiques.

Made available in DSpace on 2018-08-01T23:19:02Z (GMT). No. of bitstreams: 1 tese_10550_Resumo da Dissertação Final de Mestrado - Rovena Lebarch Rocha pdf..pdf: 25276 bytes, checksum: ecb553d4085628ef9bdd308dfb56bd3c (MD5) Previous issue date: 2018-02-28 / Pesquisas comprovam que o uso do yacon e derivados trazem benefícios à saúde humana, como melhoria da saúde intestinal, redução dos fatores de risco associados à diabetes, aumento da absorção de minerais, redução de triglicerídeos hepáticos e do ganho de peso e melhoria da resposta imune. Esses benefícios estão relacionados, principalmente, a alta concentração de FOS. Por possuir alto teor de água e, consequentemente, alta perecibilidade, a secagem do yacon trata-se de uma tecnologia eficiente por aumentar a vida útil do produto. Dentre os métodos de secagem, a secagem em leito de espuma apresenta como vantagens o menor tempo de execução, emprego de baixas temperaturas e preservação da qualidade nutricional do alimento. Desse modo, os objetivos deste trabalho foram avaliar as características físico-químicas do pó solúvel de polpa de yacon, obtido por meio da secagem de leito em espuma a 60 ºC e verificar a aceitação sensorial do pó reconstituído. Para condução dos experimentos foi adotado o Delineamento Composto Central Rotacional, a fim de investigar as concentrações ideias dos agentes espumantes Emustab® e Whey Protein na produção da espuma da polpa de yacon. Para definição ótima da concentração dos agentes espumantes foi utilizado uma função desejabilidade considerando as seguintes variáveis respostas, para: (a) espuma: massa específica e índice de coalescência; (b) pó solúvel: teor de água, solubilidade, molhabilidade e fibra solúvel; (c) secagem: tempo de secagem; e (d) análise sensorial do pó reconstituído: aceitação sensorial. Complementando os estudos foram modeladas a cinética da secagem em leito de espuma da polpa de yacon. Constatou-se que os efeitos dos agentes espumantes na produção da espuma de polpa de yacon foram significativos para o índice de coalescência, massa específica e tempo de secagem, molhabilidade, solubilidade, teor de água dos pós e aceitação sensorial (aroma, cor, sabor e impressão global) do pó reconstituído. O modelo de Midili foi o que propiciou melhor ajuste para descrever as curvas de secagem. Verificou-se que a concentração dos agentes espumantes 4,62% de Emustab® e 0,48% Whey Protein propiciou o maior índice de desejabilidade global (0,9503). O pó obtido com a concentração ótima dos agentes espumantes apresentou boa solubilidade e boa aceitação sensorial (sabor, aroma e impressão global). O conteúdo de FOS no processamento do pó de polpa de yacon manteve-se alto.

Although the perifornical lateral hypothalamic area (PeFLH), which contains orexin/hypocretin (OX) neurons, plays an important role in arousal-related behaviors, its neuromodulatory inputs are incompletely understood. The present study examined the role of glutamatergic inputs to the PeFLH in various arousal-related behaviors. Adult male rats received a microinjection of the ionotropic glutamate receptor agonists AMPA (1 and 2 mM) or NMDA (1 and 10 mM), or vehicle into the PeFLH, and were placed in an open field; 90 min later, rats were perfused for immunohistochemistry for OX and c-Fos as a marker of neuronal activation. AMPA injections dose-dependently increased locomotion, rearing, and drinking. NMDA injections (at 10 mM) increased locomotion and feeding. All these behaviors (except feeding) were positively correlated with the number of c-Fos/OX-immunoreactive neurons. These results support the role of ionotropic glutamate receptors on OX (and other) neurons in the PeFLH in the regulation of locomotor and ingestive behaviors.

The bed nucleus of the stria terminalis (BST) is a basal forebrain cluster of several distinct nuclei. It has been proposed that the BST coordinates autonomic, neuroendocrine, and behavioral functions through the integration and organization of homeostatic responses necessary for survival. Dysfunction of the BST contributes to pathophysiological states such as addiction, anxiety and aggression. Based on anatomical and behavioral studies, the BST could be a key contributor to descending modulation of nociception as well as the physiological responses related to the affective aspect of the pain experience. The objective of the present study was to further understand the neurophysiological bases underlying the involvement of the 7 anterior nuclei of the BST in pain. Using c-Fos as an indicator of neuronal activation, the results demonstrate that acute noxious stimulation produced an increase in the number of c-Fos immunoreactive cells (c-Fos-IR) in the dorsal anteromedial (dAM) and fusiform (FU) nuclei, while non-noxious stimulation did not increase c-Fos-IR in any of the nuclei examined. Chronic neuropathic pain induced by chronic constriction injury (CCI) did not alter basal c-Fos-IR in the FU or dAM. Unlike in the naïve condition, the number of c-fos-IR cells in the FU induced by acute noxious stimulation was attenuated in animals with either CCI or sham surgery compared to naive rats. In contrast, c-Fos-IR induced by acute noxious stimulation in the dAM was not affected by CCI or sham surgery. Acute noxious stimulation in animals that received CCI exhibited increased c-Fos expression in the ventromedial (vAM) nucleus of the BST, a finding not evident in naïve or sham control groups. Finally, there was an increase in c-Fos-IR in the oval (OV) nucleus of sham-operated, but not naive or CCI rats. This study reveals for the first time that pain induces neuronal activity in the BST in a nuclei- and condition-specific way. Given the efferent projection patterns from the BST, this system may relay supraspinal information to the periphery to produce physiological responses related to the affective pain experience. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2007-09-28 14:36:55.632

A number of computational methods have suggested means by which gene transcription – the process through which RNA is created from DNA – is activated, but there are factors at work that no model has been able to fully explain. In eukaryotes, gene regulation is quite complex, so models have primarily focused on a relatively simple species, Saccharomyces cerevisiae (budding yeast). Because of the inherent complexity in higher species, and even in yeast, a method of identifying transcription factor (TF) binding motifs (specific, short DNA sequences) must be efficient and thorough in its analysis. This thesis shows that a method using the Fast Orthogonal Search (FOS) algorithm to uncover binding motifs as well as cooperatively binding groups of motifs can explain variations in gene expression profiles, which reflect the level at which DNA is transcribed into RNA for a number of genes. The algorithm is very fast, exploring a motif list and constructing a final model within seconds to a few minutes. It produces model terms that are consistent with known motifs, while also revealing new motifs and interactions, and it causes impressive reductions in variance with relatively few model terms over the cell-cycle. / Thesis (Master, Electrical & Computer Engineering) -- Queen's University, 2008-08-21 10:30:24.293

We studied the expression of c-fos in medullary serotonergic neurons after a locomotor task on a treadmill in adult mice. We used a transgenically modified line in which serotonergic cells expressed enhanced yellow fluorescent protein (eYFP). We counted and plotted cells using Micro Bright Field Co. software. We determined the location of the serotonergic cells in this mouse line in the adult. We found an increase in the number of eYFP-positive cells expressing c-fos after a locomotor task in the raphe and PPR between bregma -6.8 and bregma -6.48 in the mouse (flanked rostrally by the seventh cranial nerve and caudally by the inferior olive). The percentage of eYFP-positive cells that expressed c-fos after the locomotor task in the raphe was 4%, whereas in the PPR the percentage was13.3%. Our results corroborate the observation that a specific group of serotonergic neurons located in the PPR are involved in locomotion.

Thesis (Ph. D.)--University of Virginia, 2000. / Includes bibliographical references (leaves 138-192). Also available online through Digital Dissertations.