Baroreflex control of heart rate (HR) is impaired in human diabetes mellitus and in large experimental models. However, baroreflex impairment in diabetic mouse models and diabetes-induced remodeling of baroreflex circuitry are not well studied. We examined the impairment of baroreflex control of heart rate (HR) and assessed structural remodeling of cardiac ganglia in the streptozotocin (STZ)-induced diabetic mouse model. FVB mice were either injected with vehicle or STZ. Group 1: mice were anesthetized and the femoral artery and vein were catheterized at the 30th day after vehicle or STZ injection. On the second day after surgery, baroreflex-mediated HR responses to sodium nitroprusside (SNP) and phenylephrine (PE)-induced mean arterial blood pressure (MABP) changes were measured in conscious mice. Group 2: Fluoro-Gold was administered (i.p.) to label cardiac ganglia in each mouse at the 25th day after vehicle or STZ injection. After another five days, animals were perfused and cardiac ganglia were examined using confocal microscopy. Compared with control, we found in STZ mice: 1) the HR decreased, but MABP did not. 2) The PE-induced increases of MABP were decreased. 3) Baroreflex bradycardia was attenuated in the rapid MABP ascending phase but the steady-state ΔHR/ΔMABP was not different at all PE doses. 4) SNP-induced MABP decreases were not different. 5) Baroreflex tachycardia was attenuated. 6) The sizes of cardiac ganglia and ganglionic principal neurons were decreased. 7) The ratio of nucleus/cell body of cardiac ganglionic neurons was increased. We conclude that baroreflex control of HR is impaired in conscious STZ mice. In addition, diabetes may induce a significant structural remodeling of cardiac ganglia. Such an anatomical change of cardiac ganglia may provide new information for the understanding of diabetes-induced remodeling of the multiple components within the baroreflex circuitry.

This study examined the development of attachment as it relates to co-regulation and vagal tone over the second half of the first year of life. Links to infants' attachment and developmental status were also examined. Symmetrical and unilateral co-regulated patterns of interactions at 6 months demonstrated significant linkages with attachment. Developmental status did not show direct linkages with attachment. Direct links between vagal tone and attachment were also not identified. Correlations between co-regulation and vagal tone at the 6 month time point were identified. Findings suggest an important role of co-regulation as it relates to attachment development. Future studies may benefit from evaluating the role of co-regulation as a mediating variable between vagal tone and attachment development.

No description available.

No description available.

Research shows that when a gender stereotype is made salient and the target of the stereotype is asked to perform in the stereotyped domain, targets of the stereotype often perform at a lower level compared to situations when the stereotype was not made salient (Spencer, Steele, & Quinn, 1999). Current models of stereotype threat show that increased physiological arousal and reduced working memory capacity partially explain this decrement in performance (Ben-Zeev, Fein, & Inzlicht, 2005; Schmader, Johns, & Forbes, 2008). Furthermore, the noticeable absence of female faculty and students in math and science departments at coed universities throughout the United States may increase the belief in gender stereotypes and discourage women from pursuing careers in these fields (Dasgupta & Asgari, 2004). Contact with counter-stereotypical exemplars, such as female science experts, decreases belief in gender stereotypes and increases women's motivation to pursue careers in science (Stout, Dasgupta, Hunsinger, & McManus, 2011). Thus, the present study examined whether imagining an interpersonal interaction with a counter-stereotypic exemplar removes the physiological and performance effects of stereotype threat. However, the stereotype threat manipulation failed to elicit a strong stereotype threat effect on performance or physiology. Only reaction time and high frequency heart rate variability were sensitive to the stereotype threat induction. The imagination manipulation significantly attenuated the physiological effects of stereotype threat, whereas the reaction time effects were only marginally significant. Limitations and future directions for stereotype threat and imagined contact are discussed. / Ph. D.

La metformine, un composé antidiabétique reste de nos jours recommandée comme traitement de première intention pour le diabète de type 2. Ses mécanismes d’action en tant que composé anti-hyperglycémiant sont de plus en plus documentés. En revanche, son action anorexigène et ses cibles centrales demeurent peu étudiées. Par ailleurs, des données croissantes de la littérature semblent indiquer que l’activité physique, souvent associée aux thérapies anti-obésité et antidiabétiques, pourrait accroitre la sensibilité des réseaux neuronaux aux signaux endogènes permettant de réguler la prise alimentaire et le poids corporel. Ceci suggère que l’efficacité des thérapies induisant des modulations d’expression de ces signalisations pourrait être directement augmentée par l’activité physique. Dans le présent travail, nous avons cherché i) à explorer les effets centraux de la metformine chez la souris et ii) à déterminer si l’activité physique pouvait potentialiser les effets de la metformine. L’ensemble de mon travail de thèse, réalisée en partenariat avec la société BIOMEOSTASIS, a permis d’apporter des éléments nouveaux quant aux mécanismes impliqués dans les effets centraux de la metformine et d’identifier la nesfatine-1 comme un acteur potentiel dans les effets anorexigènes de ce composé. / Metformin, an antidiabetic compound, still remains a first-line treatment for type 2 diabetes. The mechanisms by which this compound exerts its antihyperglycemic effect are increasingly documented. However, its anorectic action and central targets remain less studied. Furthermore, increasing data in the literature suggest that physical activity, commonly associated with anti-obesity and anti-diabetic therapies, may increase neural networks’ sensitivity to endogenous signals involved in food intake and body weight control. This suggests that the efficacy of therapies inducing expression modulation of these signals may be directly enhanced by physical activity. In the present study, we sought i) to explore the central effects of metformin in mice and, ii) determine whether physical activity could potentiate the effects of metformin. All my work, in partnership with the company BIOMEOSTASIS brought new elements about mechanisms involved in the central effects of metformin and identified nesfatin-1 as a potential actor for the anorectic effects of this compound.

Le contrôle central de la balance énergétique implique un réseau neuronal fortement régulé et distribué dans l’hypothalamus et le complexe vagal dorsal (CVD). Au sein de ces structures, les neurones exprimant la pro-opiomélanocortine (POMC) jouent un rôle prépondérant pour limiter la taille des repas et augmenter les dépenses énergétiques. Ainsi l’activité de ces neurones est modulée par la leptine, une hormone qui reflète l’état de réserve énergétique. Les microARN (miARN) sont des ARN non codant de 22 à 26 nucléotides qui régulent l’expression des gènes par appariement spécifique avec des ARNm cibles. Actuellement, le rôle des miARN dans la régulation de la balance énergétique au niveau central reste à être clarifié. Dans ce contexte, nous avons développé un modèle de souris transgéniques qui présentent une perte de l’expression de l’enzyme de maturation des miARN DICER dans les cellules exprimant la POMC. Une augmentation de la sensibilité hypothalamique à la leptine a été observée chez les animaux invalidés ce qui suggère un rôle important des miARN dans le contrôle de l’activité des neurones à POMC par la leptine. Alors, nous avons entrepris d’identifier et de caractériser les miARN qui ciblent potentiellement l’ARNm de la POMC. Une fois identifié les miARN candidats par une approche in silico, l’étude des souris obèses déficientes en leptine (ob/ob) ou en son récepteur (db/db) a montré que l’expression hypothalamique de miR-383, miR-384-3p et miR-488 était augmentée. De plus, l’administration périphérique de leptine chez les souris ob/ob a restauré l’expression de ces miARN à des niveaux semblables à ceux observés chez les animaux non obèses. / The central control of energy balance involves a highly regulated neuronal network within the hypothalamus and the dorsal vagal complex (DVC). In these structures, pro-opiomelanocortin (POMC) neurons are known to reduce meal size and to increase energy expenditure. Thus, leptin, a peripheral signal that relays information regarding body fat content, modulates the activity of POMC neurons. MicroRNAs (miRNAs) are short non-coding RNAs of 22-26 nucleotides that post-transcriptionally interfere with target gene expression by binding to their mRNAs. To date, the role of the miRNAs in the control of energy balance remains to be clarified. In this context, we developed a transgenic mouse model with a deletion of the miRNA processing enzyme DICER specifically in POMC cells. Conditional deletion of Dicer in POMC cells leads to an increase in hypothalamic leptin sensitivity. These results suggest an important role of miRNAs in the leptin-dependent POMC neuron activity. Next, we identified and characterized the miRNAs that potentially target POMC mRNA. After the selection of miRNA of interest by in silico approach, we observed that miR-383, miR-384-3p, and miR-488 expressions were up-regulated in the hypothalamus of leptin deficient ob/ob mice. In accordance with these observations, we showed that miR-383, miR-384-3p and miR-488 were also increased in db/db mice that exhibit a non-functional leptin receptor. The intraperitoneal injection of leptin down-regulated the expression of these miRNAs of interest in the hypothalamus of ob/ob mice, thus showing the involvement of leptin in the expression of miR-383, miR-384-3p and miR-488.

Le maintien de notre poids corporel résulte d'un équilibre entre les dépenses et les apports énergétiques. Cet équilibre appelé « homéostasie énergétique » implique un grand nombre de molécules. Parmi elles, la nesfatine-1, découverte en 2006, est un peptide de 82 acides aminés issu du clivage de la protéine NUCB2. L'intérêt généré par la nesfatine-1 réside dans son action anorexigène exercée indépendamment de la signalisation à la leptine. La nesfatine-1 est exprimée dans plusieurs organes tels que le tissu adipeux, l'estomac, le pancréas, ainsi que le cerveau. Dans le cerveau, son expression se limite principalement à quelques groupes neuronaux localisés dans l'hypothalamus et le complexe vagal dorsal. Au cours de ce travail, nous avons analysé la sensibilité des neurones exprimant NUCB2/nesfatine-1 aux signaux périphériques physiologiques et physiopathologiques affectant la prise alimentaire. Nous montrons que ces neurones sont sensibles à une hypoglycémie et qu'ils pourraient contribuer à la contre-régulation mise en place afin de rétablir la glycémie de base. De plus, nous montrons qu'ils sont activés en réponse à deux stimuli inflammatoires : l'administration de lipopolysaccharide et l'intoxication alimentaire avec une mycotoxine appelée déoxynivalénol. Ainsi, les neurones exprimant NUCB2/nesfatine-1 pourraient contribuer au développement de l'anorexie inflammatoire. Cette étude a constitué la première mise en évidence d'une implication de ce peptide en situation pathologique. L'ensemble de ces résultats suggère qu'en plus de son effet satiétogène, la nesfatine-1 participe à la signalisation centrale impliquée dans la glucodétection et les réponses inflammatoires. / The long term maintenance of body weight results from a balance between energy expenditure and intake. This balance, called “energy homeostasis”, involves a large number of molecules. Among these, nesfatin-1, discovered in 2006, is an 82 amino-acid peptide derived from the cleavage of the protein NUCB2. The interest generated by nesfatin-1 lies in its anorexigenic effect performed independently of leptin signalization. Nesfatin-1 is expressed in several organs such as adipose tissue, stomach, pancreas, and brain. In the brain, its expression is limited to a few neuronal groups located in the hypothalamus and dorsal vagal complex. In this work, we analyzed the sensitivity of NUCB2/nesfatin-1-expressing neurons to physiological and physiopathological peripheral signals affecting food intake. We show that these neurons are sensitive to hypoglycemia and that they could contribute to the counter-regulatory response established in order to restore the basal blood glucose level. Moreover, we show that they are activated in response to two inflammatory stimuli: lipopolysaccharide administration and food intoxication with a mycotoxin named deoxynivalenol. So, NUCB2/nesfatin-1-expressing neurons could contribute to the development of inflammatory anorexia. This study was the first evidence of an involvement of this peptide in a pathological situation. Taken together, these results suggest that in addition to its satiating effect, nesfatin-1 participates in the central signalization involved in glucodetection and inflammatory responses.

Utilizando Análise Espectral (FFT) para quantificar a variabilidade autonômica no animal intacto, analisamos pressão arterial, intervalo de pulso (IP) e fluxo sangüíneo no repouso e no exercício, em ratos normotensos (WKY) e hipertensos (SHR), sedentários (S) ou treinados (T), após pré-tratamento do NTS/DMV com veículo e antagonista de ocitocina (OTant). As principais alterações foram relacionadas à freqüência cardíaca (FC) e ao IP: bradicardia de repouso em WKYT e SHRT; aumento na resposta taquicárdica do exercício após OTant apenas nos WKYT. No repouso, os SHR apresentaram queda da variância do IP com diminuição dos componentes de baixa (LF-simpático) e alta (HF-vago) freqüências, corrigidas pelo T. No exercício houve queda dos componentes espetrais do IP nos grupos experimentais, exceto o HF que não diminuiu nos WKYT. OTant no NTS/DMV reduziu o HF dos SHRT no repouso e exercício; a ausência da queda do HF nos WKYT foi abolida. Resultados indicam a importância da ocitocina agindo sobre o vago na modulação da FC basal e da taquicardia do exercício apenas em T. / Using Spectral Analysis (FFT) to quantify the autonomic variability in intact animal, we analyzed blood pressure, pulse interval (PI) and blood flow at rest and during exercise, in normotensive (WKY) and hypertensive (SHR) rats, sedentary (S) or trained (T), after solitary vagal complex (NTS/DMV) pre-treatment with vehicle and oxytocin antagonist (OTant). The main changes were related to heart rate (HR) and PI: rest bradycardia in WKYT and SHRT; increased exercise tachycardia after OTant only in WKYT. At rest, SHR presented a fall of in PI variance with decreased low (LF-simpathetic) and high (HF-vagal) frequencies components that were normalized by T. During exercise, the spectral components decreased in the experimental groups, except HF unchanged in WKYT. OTant into the NTS/DMV reduced the HF of the SHRT at rest and exercise; the absence of the fall in HF of WKYT was abolished. Results indicate the importance of oxytocin acting on vagus in the modulation of basal HR and exercise tachycardia only in T rats.

Submitted by Sara Ribeiro (sara.ribeiro@ucb.br) on 2018-08-08T14:11:40Z No. of bitstreams: 1 ArilsonFernandesMendoncadeSousaTese2018.pdf: 5768876 bytes, checksum: 66d7e7ce78b9d2a4b54e615ac9d3282d (MD5) / Approved for entry into archive by Sara Ribeiro (sara.ribeiro@ucb.br) on 2018-08-08T14:11:52Z (GMT) No. of bitstreams: 1 ArilsonFernandesMendoncadeSousaTese2018.pdf: 5768876 bytes, checksum: 66d7e7ce78b9d2a4b54e615ac9d3282d (MD5) / Made available in DSpace on 2018-08-08T14:11:52Z (GMT). No. of bitstreams: 1 ArilsonFernandesMendoncadeSousaTese2018.pdf: 5768876 bytes, checksum: 66d7e7ce78b9d2a4b54e615ac9d3282d (MD5) Previous issue date: 2018-05-25 / Only two weeks of sprint interval training (SIT) has been shown to be associated with positive changes in aerobic capacity and cardiac autonomic control. Both aerobic capacity and autonomic control have been shown to be positively associated with improved attention. However, to date, the relationship between this type of training and attention has not been investigated yet. The aim of the present study was to investigate the influence of two weeks of SIT on aerobic capacity, cardiac autonomic control and attention components in healthy university students; Also, to verify if the training fidelity would influence these adaptations. One hundred and nine participants were divided into experimental (EG) and control (CG) groups. EG performed a SIT program consisting of 6 sessions of maximal 4 × 30 s all-out efforts on a cycle ergometer, interspersed with active 4-minute rests. The criterion for fidelity was to reach> 90% of the estimated maximum heart rate (HR) during sprint sessions. After analysis, EG was divided into fidelity groups HIGH (n = 26) and LOW (n = 46), respectively. The attention components were evaluated through the Attention Network Test (ANT). The aerobic capacity (VO2max) was estimated according to Astrand's nomogram while the sum of the skinfolds: pectoral, triceps, subscapular, medial axillary, abdomen, suprailiac and thigh was verified. Autonomic HR control was assessed by HR variability (HRV) and HR complexity at rest and during ANT, before and after six sessions of SIT. Both HIGH and LOW significantly increased aerobic capacity, vagal modulation before and during ANT and executive control, and decreased body fat after SIT (p <0.05). However, only HIGH participants showed an increase in HR complexity and accuracy in ANT responses when compared to LOW (p <0.05). Two weeks of SIT improved executive control, body fat, aerobic capacity and autonomic control in university students, with better results reported for the HIGH group. / Apenas duas semanas de treinamento intervalado de esforços supra máximos (TIsm) tem mostrado estar associado com modificações positivas na capacidade aeróbia e controle autonômico cardíaco. Tanto a capacidade aeróbia, como o controlo autonômico demonstram estar associados positivamente com melhoria da atenção. Entretanto, até o presente momento a relação entre este tipo de treinamento e atenção não foi investigada. O objetivo do presente estudo foi investigar a influência de um programa de TIsm na capacidade aeróbia, controle autonômico cardíaco e componentes da atenção em jovens universitários saudáveis; ainda, verificar se a fidelidade do treinamento influenciaria essas adaptações. Cento e nove participantes foram divididos em grupo experimental (GE) e controle (GC). O GE realizou um programa TIsm que consistiu em 6 sessões de TIsm de 4 × 30 s em um cicloergômetro, intercaladas com descansos ativos de 4 min. O critério para fidelidade foi atingir> 90% da frequência cardíaca máxima estimada (FC) durante as sessões de TIsm. Após as análises, o GE foi dividido em grupos de fidelidade alta, GEA (n = 26) e baixa, GEB (n = 46), respectivamente. Os componentes da atenção foram avaliados por meio do Teste de Rede de Atenção (ANT). A capacidade aeróbia (VO2max) foi estimada segundo o nomograma de Astrand enquanto o somatório de dobras cutâneas: peitoral, tríceps, subescapular, axilar média, abdômen, supra-ilíaca e coxa foi realizada. O controle autonômico da FC foi avaliado por meio da VFC e complexidade da FC em repouso e durante o ANT, antes e depois de seis sessões de TIsm. Ambos GEA e GEB aumentaram significativamente a capacidade aeróbia, modulação vagal antes e durante a realização do ANT e o controle executivo e diminuição da gordura corporal após o TIsm (p <0,05). No entanto, apenas os participantes do GEA apresentaram um aumento na complexidade da FC e acurácia nas respostas do ANT quando comparados ao GEB (p <0,05). Duas semanas de TIsm melhoraram o controle executivo, a gordura corporal, a capacidade aeróbia e o controle autonômico em estudantes universitários, com melhores resultados relatados para o grupo com GEA fidelidade.