Browsing by Author "Campos, Glenda Siqueira Viggiano"

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    Association of high-fat diet with neuroinflammation, anxiety-like defensive behavioral responses, and altered thermoregulatory responses in male rats.
    (2019) Noronha, Sylvana Izaura Salyba Rendeiro de; Lima, Paulo Marcelo de; Campos, Glenda Siqueira Viggiano; Chírico, Máira Tereza Talma; Abreu, Aline Rezende Ribeiro de; Figueiredo, Amanda Braga de; Silva, Fernanda Cacilda dos Santos; Chianca Júnior, Deoclécio Alves; Lowry, Christopher; Menezes, Rodrigo Cunha Alvim de
    Overweight and obesity are a worldwide pandemic affecting billions of people. These conditions have been associated with a chronic low-grade inflammatory state that is recognized as a risk factor for a range of somatic diseases as well as neurodevelopmental disorders, anxiety disorders, trauma- and stressor-related disorders, and affective disorders. We previously reported that the ingestion of a high-fat diet (HFD; 45% fat kcal/g) for nine weeks was capable of inducing obesity in rats in association with increased reactivity to stress and increased anxiety-related defensive behavior. In this study, we conducted a nine-week diet protocol to induce obesity in rats, followed by investigation of anxiety-related defensive behavioral responses using the elevated T-maze (ETM), numbers of FOS-immunoreactive cells after exposure of rats to the avoidance or escape task of the ETM, and neuroinflammatory cytokine expression in hypothalamic and amygdaloid nuclei. In addition, we investigated stress-induced cutaneous thermoregulatory responses during exposure to an open-field (OF). Here we demonstrated that nine weeks of HFD intake induced obesity, in association with increased abdominal fat pad weight, increased anxiety-related defensive behavioral responses, and increased proinflammatory cytokines in hypothalamic and amygdaloid nuclei. In addition, HFD exposure altered avoidance- or escape task-induced FOSimmunoreactivity within brain structures involved in control of neuroendocrine, autonomic, and behavioral responses to aversive stimuli, including the basolateral amygdala (BLA) and dorsomedial (DMH), paraventricular (PVN) and ventromedial (VMH) hypothalamic nuclei. Furthermore, rats exposed to HFD, relative to control dietfed rats, responded with increased tail skin temperature at baseline and throughout exposure to an open-field apparatus. These data are consistent with the hypothesis that HFD induces neuroinflammation, alters excitability of brain nuclei controlling neuroendocrine, autonomic, and behavioral responses to stressful stimuli, and enhances stress reactivity and anxiety-like defensive behavioral responses.
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    Efeito do tratamento crônico com losartana, um bloqueador de receptores AT1, sobre o comportamento de ansiedade, depressão e memória de ratas ovariectomizadas.
    (2019) Campos, Glenda Siqueira Viggiano; Menezes, Rodrigo Cunha Alvim de; Oliveira, Antônio Carlos Pinheiro de; Silva, Fernanda Cacilda dos Santos; Fontes, Marco Antônio Peliky; Leite, Romulo
    A privação de hormônios ovarianos está associada a disfunções em mulheres na pós-menopausa. Estudos em roedores têm revelado que a privação hormonal induz alterações no hipocampo e amígdala, e também na atividade do sistema renina angiotensina (SRA). A alta expressão de receptores AT1 no hipocampo e na amígdala sugere o envolvimento do SRA na modulação de respostas emocionais e cognitivas. De fato, tem-se notado o efeito neuroprotetor dos bloqueadores de receptores de AT1 (BRAs), no entanto, até onde sabemos, não há estudos avaliando os efeitos dos BRAs sobre as respostas cognitivas e emocionais resultantes da depleção de hormônios ovarianos. Assim, o objetivo deste trabalho é avaliar o efeito da privação de hormônios ovarianos e do tratamento crônico com o BRA losartana sobre o comportamento do tipo ansiedade, depressão e memória de ratas ovariectomizadas. Inicialmente avaliamos o efeito do ciclo estral e de 3 semanas de ovariectomia (OVX) em ratas Fischer sobre o comportamento do tipo ansiedade e pânico avaliados no labirinto em T elevado (LTE), campo aberto (CA) e paradigma claro/escuro (PCE). Adiante, ratas Long Evans Sham e OVX foram tratadas com água natural ou losartana durante 10 semanas. A partir da quinta semana as ratas foram avaliadas no labirinto em cruz elevado (LCE), CA, reconhecimento de novo objeto (RNO), ameaça iminente (AI) e preferência por sacarose (PS). O encéfalo foi removido na 10ª semana para avaliação da expressão gênica de AT1 no hipocampo. Nossos resultados mostram que o ciclo estral não influenciou o comportamento do tipo ansiedade e pânico. Já as ratas OVX apresentaram aumento da latência de esquiva inibitória (Esq1: p = 0,038; Esq2: p = 0,032, teste Mann-Whitney) e redução da fuga no LTE (Fuga 1: p = 0,012, teste t de Student), e menor tempo no compartimento claro do PCE (p = 0,0417, teste t de Student), que são respostas indicativas de ansiedade. A ovariectomia também induziu comportamento do tipo ansiedade no LCE e déficit de memória avaliada no RNO. O tratamento com losartana foi capaz de prevenir tais alterações no grupo OVX, exibindo respostas semelhantes aos grupos Sham-Veículo e Sham-Losartana (tempo: F (1, 52) = 7,78; p = 0,007; entradas: F (1, 52) = 5; p = 0,02; IR: F (1, 55) = 4,99; p = 0,03, two-way ANOVA). O tratamento aumentou a expressão de RNAm de AT1 no hipocampo (F (1, 23) = 4,74; p = 0,04, two-way ANOVA) independente da cirurgia. Concluímos que o tratamento com losartana foi capaz de prevenir comportamento do tipo ansiedade e déficit de memória de curto prazo induzidos pela privação de hormônios ovarianos em ratas ovariectomizadas.
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    Estrogen receptor β activation within dorsal raphe nucleus reverses anxiety-like behavior induced by food restriction in female rats.
    (2018) Campos, Glenda Siqueira Viggiano; Noronha, Sylvana Izaura Salyba Rendeiro de; Souza, Aline Maria Arlindo de; Lima, Paulo Marcelo de Andrade; Abreu, Aline Rezende Ribeiro de; Chianca Júnior, Deoclécio Alves; Menezes, Rodrigo Cunha Alvim de
    Severe food restriction (FR), as observed in disorders like anorexia nervosa, has been associated to the reduction of estrogen levels, which in turn could lead to anxiety development. Estrogen receptors, mainly ERβ type, are commonly found in the dorsal raphe nucleus (DRN) neurons, an important nucleus related to anxiety modulation and the primary source of serotonin (5-HT) in the brain. Taking together, these findings suggest an involvement of estrogen in anxiety modulation during food restriction, possibly mediated by ERβ activation in serotonergic DRN neurons. Thus, the present study investigated the relationship between food restriction and anxiety-like behavior, and the involvement of DRN and ERβ on the modulation of anxiety-like behaviors in animals subjected to FR. For that, female Fischer rats were grouped in control group, with free access to food, or a FR group, which received 40% of control intake during 14 days. Animals were randomly treated with 17β-estradiol (E2), DPN (ERβ selective agonist), or their respective vehicles, PBS and DMSO. Behavioral tests were performed on Elevated T-Maze (ETM) and Open Field (OF). Our results suggest that FR probably reduced the estrogen levels, since the remained in the non-ovulatory cycle phases, and their uterine weight was lower when compared to control group. The FR rats showed increased inhibitory avoidance latency in theETM indicating that FR is associated with the development of an anxiety-like state. The injections of both E2 and DPN into DRN of FR animals had an anxiolytic effect. Those data suggest thatanxiety-like behavior induced by FR could be mediated by a reduction of ERβ activation in the DRN neurons, probably due to decreased estrogen levels.
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    High fat diet induced-obesity facilitates anxiety-like behaviors due to GABAergic impairment within the dorsomedial hypothalamus in rats.
    (2017) Noronha, Sylvana Izaura Salyba Rendeiro de; Campos, Glenda Siqueira Viggiano; Abreu, Aline Rezende Ribeiro de; Souza, Aline Maria Arlindo de; Chianca Júnior, Deoclécio Alves; Menezes, Rodrigo Cunha Alvim de
    Overweight and obesity are conditions associated with an overall range of clinical health consequences, and they could be involved with the development of neuropsychiatric diseases, such as generalized anxiety disorder (GAD) and panic disorder (PD). A crucial brain nuclei involved on the physiological functions and behavioral responses, especially fear, anxiety and panic, is the dorsomedial hypothalamus (DMH). However, the mechanisms underlying the process whereby the DMH is involved in behavioral changes in obese rats still remains unclear. The current study further investigates the relation between obesity and generalized anxiety, by investigating the GABAA sensitivity to pharmacological manipulation within the DMH in obese rats during anxiety conditions. Male Wistar rats were divided in two experimental groups: the first was fed a control diet (CD; 11% w/w) and second was fed a high fat diet (HFD; 45% w/w). Animals were randomly treated with muscimol, a GABAA agonist and bicuculline methiodide (BMI), a GABAA antagonist. Inhibitory avoidance and escape behaviors were investigated using the Elevated T-Maze (ETM) apparatus. Our results revealed that the obesity facilitated inhibitory avoidance acquisition, suggesting a positive relation between obesity and the development of an anxiety-like state. The injection of muscimol (an anxiolytic drug), within the DMH, increased the inhibitory avoidance latency in obese animals (featuring an anxiogenic state). Besides, muscimol prolonged the escape latency and controlling the possible panic-like behavior in these animals. Injection of BMI into the DMH was ineffective to produce an anxiety-like effect in obese animals opposing the results observed in lean animals. These findings support the hypotheses that obese animals are susceptible to develop anxiety-like behaviors, probably through changes in the GABAergic neurotransmission within the DMH.
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    Influência do estradiol nos transtornos de ansiedade em ratas fischer submetidas à restrição alimentar.
    (2015) Campos, Glenda Siqueira Viggiano; Menezes, Rodrigo Cunha Alvim de; Viana, Milena de Barros de; Oliveira, Lisandra Brandino de
    A restrição alimentar (RA) severa provoca carência energética e nutricional, levando o indivíduo à desnutrição, e este desequilíbrio acarreta inúmeras consequências bioquímicas, fisiológicas e emocionais, tais como ansiedade, pânico e danos à memória. A RA também altera o eixo hipotálamo-hipófise-ovariano, que é a via que regula a produção de hormônios ovarianos, ocasionando redução da síntese e liberação de estradiol pelos ovários. Estudos já mostraram a presença de alta densidade de receptores de estradiol do tipo β (ERβ), que quando ativados resultam em efeitos ansiolíticos, no núcleo dorsal da rafe (NDR), indicando uma relação entre o estradiol, o NDR e os transtornos de ansiedade generalizada (TAG) e pânico (TP). O NDR é uma importante estrutura encefálica relacionada a fisiopatologia dos TAG e TP. Assim, o nosso objetivo foi investigar a influência do estradiol no NDR sobre os TAG e TP em ratas submetidas à restrição alimentar. Para isso, ratas Fischer (210 ± 10g) foram divididas em controle (C) e RA e alojadas individualmente. Durante 14 dias, as C receberam ração ad libitum e os RA receberam 40% do consumo médio dos C. No 7° dia foram anestesiados com ketamina-xilazina para inserção de cânula-guia no NDR. Ao final do protocolo dietético, cada animal foi submetido a dois diferentes ensaios nos quais ou veículo (100 nL) ou estradiol (0,5 pmol/100 nL) foi microinjetado no NDR. Após 20 minutos, as ratas foram testadas no Labirinto em T Elevado (LTE), um aparato que permite avaliar comportamento de ansiedade (esquiva inibitória) e pânico (fuga), e em seguida foram colocadas no campo aberto (arena retangular que avalia a atividade locomotora do animal). No dia seguinte as ratas foram testadas novamente no LTE para avaliação da memória. Nossos resultados mostraram que as ratas RA possuíam o útero mais leve em relação às controle, sugerindo que a RA alimentar reduz a concentração de hormônios ovarianos, entre eles o estradiol. Nós também observamos que as RA levaram mais tempo para sair do braço fechado do LTE do que as C durante a esquiva (F1,63 = 10,34; p = 0,0021), o que indica um comportamento mais ansioso pelo grupo RA. Ao microinjetarmos estradiol no NDR das ratas RA, notou-se que o tempo de latência de saída do braço fechado diminuiu em relação àquelas que receberam veículo (F2,65 = 3,86; p=0,0002), sugerindo que o estradiol agiu como um agente ansiolítico revertendo o comportamento ansioso apresentado no experimento anterior. Não encontramos diferença entre os grupos no tempo de latência de fuga. Em relação à atividade locomotora, as ratas RA mostraram-se menos ativas que as C, independente da administração de veículo ou estradiol no NDR. Diante disso, sugerimos que a RA reduz os níveis de estradiol, diminuindo a concentração disponível deste XVI hormônio para atuar nos receptores presentes no NDR, o que altera o controle desta via, levando ao comportamento de ansiedade nas ratas.
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    New insights on amygdala : basomedial amygdala regulates the physiological response to social novelty.
    (2016) Mesquita, Laura Batista Tavares; Abreu, Aline Rezende Ribeiro de; Abreu, Alessandra Rezende Ribeiro de; Souza, Aline Maria Arlindo de; Noronha, Sylvana Izaura Salyba Rendeiro de; Silva, Fernanda Cacilda dos Santos; Campos, Glenda Siqueira Viggiano; Chianca Júnior, Deoclécio Alves; Menezes, Rodrigo Cunha Alvim de
    The amygdala has been associated with a variety of functions linked to physiological, behavioral and endocrine responses during emotional situations. This brain region is comprised of multiple sub-nuclei. These subnuclei belong to the same structure, but may be involved in different functions, thereby making the study of each sub-nuclei important. Yet, the involvement of the basomedial amygdala (BMA) in the regulation of emotional states has yet to be defined. Therefore, the aim of our study was to investigate the regulatory role of the BMA on the responses evoked during a social novelty model and whether the regulatory role depended on an interaction with the dorsomedial hypothalamus (DMH). Our results showed that the chemical inhibition of the BMA by the microinjection of muscimol (c-aminobutyric acid (GABAA) agonist) promoted increases in mean arterial pressure (MAP) and heart rate (HR), whereas the chemical inhibition of regions near the BMA did not induce such cardiovascular changes. In contrast, the BMA chemical activation by the bilateral microinjection of bicuculline methiodide (BMI; GABAA antagonist), blocked the increases in MAP and HR observed when an intruder rat was suddenly introduced into the cage of a resident rat, and confined to the small cage for 15 min. Additionally, the increase in HR and MAP induced by BMA inhibition were eliminated by DMH chemical inhibition. Thus, our data reveal that the BMA is under continuous GABAergic influence, and that its hyperactivation can reduce the physiological response induced by a social novelty condition, possibly by inhibiting DMH neurons.
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    Severe food restriction activates the central renin angiotensin system.
    (2020) Souza, Aline Maria Arlindo de; Linares, Andrea; Speth, Robert; Campos, Glenda Siqueira Viggiano; Ji, Hong; Chianca Júnior, Deoclécio Alves; Sandberg, Kathryn; Menezes, Rodrigo Cunha Alvim de
    We previously showed that 2 weeks of a severe food restricted (sFR) diet (40% of the caloric intake of the control (CT) diet) up-regulated the circulating renin angiotensin (Ang) system (RAS) in female Fischer rats, most likely as a result of the fall in plasma volume. In this study, we investigated the role of the central RAS in the mean arterial pressure (MAP) and heart rate (HR) dysregulation associated with sFR. Although sFR reduced basal mean MAP and HR, the magnitude of the pressor response to intracerebroventricular (icv) microinjection of Ang-[1-8] was not affected; however, HR was 57 ± 13 bpm lower 26 min after Ang-[1-8] microinjection in the sFR rats and a similar response was observed after losartan was microinjected. The major catabolic pathway of Ang-[1-8] in the hypothalamus was via Ang-[1-7]; however, no differences were detected in the rate of Ang-[1-8] synthesis or degradation between CT and sFR animals. While sFR had no effect on the AT1R binding in the subfornical organ (SFO), the organum vasculosum laminae terminalis (OVLT) and median preoptic nucleus (MnPO) of the paraventricular anteroventral third ventricle, ligand binding increased 1.4-fold in the paraventricular nucleus (PVN) of the hypothalamus. These findings suggest that sFR stimulates the central RAS by increasing AT1R expression in the PVN as a compensatory response to the reduction in basal MAP and HR. These findings have implications for people experiencing a period of sFR since an activated central RAS could increase their risk of disorders involving over activation of the RAS including renal and cardiovascular diseases.
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    Tobacco-free cigarette smoke exposure induces anxiety and panic-related behaviours in male wistar rats.
    (2018) Chírico, Máira Tereza Talma; Bezerra, Frank Silva; Guedes, Mariana Reis; Souza, Ana Beatriz Farias de; Silva, Fernanda Cacilda dos Santos; Campos, Glenda Siqueira Viggiano; Noronha, Sylvana Izaura Salyba Rendeiro de; Mesquita, Laura Batista Tavares; Reis, Thayane Oliveira; Cangussú, Silvia Dantas; Chianca Júnior, Deoclécio Alves; Menezes, Rodrigo Cunha Alvim de
    Smokers, who generally present with lung damage, are more anxious than non-smokers and have an associated augmented risk of panic. Considering that lung damage signals specific neural pathways that are related to affective responses, the aim of the present study was to evaluate the influence of pulmonary injury on anxiety and panic-like behaviours in animals exposed to cigarette smoke with and without tobacco. Male Wistar rats were divided into the following groups: a control group (CG); a regular cigarette group (RC); and a tobacco-free cigarette (TFC) group. Animals were exposed to twelve cigarettes per day for eight consecutive days. The animals were then exposed to an elevated T-maze and an open field. The RC and TFC groups presented increases in inflammatory cell inflow, antioxidant enzyme activity, and TBARS levels, and a decrease in the GSH/GSSG ratio was observed in the TFC group. Exposure to RC smoke reduced anxiety and panic-related behaviours. On the other hand, TFC induced anxiety and panic-related behaviours. Thus, our results contradict the concept that nicotine is solely accountable for shifted behavioural patterns caused by smoking, in that exposure to TFC smoke causes anxiety and panic-related behaviours.