Browsing by Author "Souza, Aline Maria Arlindo de"

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    Amygdalar neuronal activity mediates the cardiovascular responses evoked from the dorsolateral periaqueductal gray in conscious rats.
    (2015) Abreu, Alessandra Rezende Ribeiro de; Santos, Laura Gomes Batista Tavares; Souza, Aline Maria Arlindo de; Silva, L. G. da; Chianca Júnior, Deoclécio Alves; Menezes, Rodrigo Cunha Alvim de
    There is ample evidence that both lateral/ dorsolateral periaqueductal gray (l/dlPAG) and basolateral amygdala (BLA) are essential for the regulation of the autonomic responses evoked during innate reactions to threatening stimuli. However, it is not well established to what extent the BLA regulates the upstream functional connection from the l/dlPAG. Here we evaluated the role of the BLA and its glutamatergic receptors in the cardiovascular responses induced by l/dlPAG stimulation in rats. We examined the influence of acute inhibition of the BLA, unilaterally, by injecting muscimol on the cardiovascular responses evoked by the injection of N-methyl D-aspartate (NMDA) into the l/dlPAG. We also evaluated the role of BLA ionotropic glutamate receptors in these responses by injecting antagonists of NMDA and AMPA/kainate receptor subtypes into the BLA. Our results show that the microinjection of NMDA in the BLA increased the mean arterial pressure (MAP) and heart rate (HR). Injection of NMDA into the l/dlPAG caused similar increases in these variables, which was prevented by the prior injection of muscimol, a GABAA agonist, into the BLA. Moreover, injection of glutamatergic antagonists (2-amino-5-phosphonopentanoate (AP5) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)) into the BLA reduced the increase in MAP and HR induced by l/dlPAG activation. Finally, the inhibition of the central amygdala neurons failed to reduce the cardiovascular changes induced by l/dlPAG activation. These results indicate that physiological responses elicited by l/dlPAG activation require the neuronal activity in the BLA. This ascending excitatory pathway from the l/dlPAG to the BLA might ensure the expression of the autonomic component of the defense reaction
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    Blunted gaba-mediated inhibition within the dorsomedial hypothalamus potentiates the cardiovascular response to emotional stress in rats fed a high-fat diet.
    (2014) Abreu, Aline Rezende Ribeiro de; Abreu, Alessandra Rezende Ribeiro de; Santos, Laura Tavares; Souza, Aline Maria Arlindo de; Silva Junior, Luiz Gonzaga da; Chianca Júnior, Deoclécio Alves; Menezes, Rodrigo Cunha Alvim de
    Rats fed a high-fat diet (HFD) present an exaggerated endocrine response to stress conditions, which, like obesity, show a high correlation with cardiovascular diseases. Meanwhile the GABAergic neurotransmission within the dorsomedial hypothalamus (DMH) is involved in the regulation of the physiological responses during emotional stress. Here we evaluated the influence of obesity, induced by a HFD, on the cardiovascular responses induced by air jet stress in rats, and the role of the GABAergic tonus within the DMH in these changes. Our results showed that consumption of a HFD (45% w/w fat) for 9 weeks induced obesity and increases in baseline mean arterial pressure (MAP) and heart rate (HR). Moreover, obesity potentiated stress responsiveness, evidenced by the greater changes in MAP and HR induced by stress in obese rats. The injection of muscimol into the DMH reduced the maximal increases in HR and MAP induced by stress in both groups; however, the reduction in the maximal increases in MAP in the HFD group was less pronounced. Moreover, the injection of muscimol into the DMH of obese rats was less effective in reducing the stress-induced tachycardia, since the HR attained the same levels at the end of the stress paradigm as after the vehicle injection. Injection of bicuculline into DMH induced increases in MAP and HR in both groups. Nevertheless, obesity shortened the tachycardic response to bicuculline injection. These data show that obesity potentiates the cardiovascular response to stress in rats due to an inefficient GABAA-mediated inhibition within the DMH.
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    Efeitos da restrição alimentar sobre o sistema renina angiotensina e sua influência nas respostas cardiovasculares de ratas Fischer.
    (2017) Souza, Aline Maria Arlindo de; Chianca Júnior, Deoclécio Alves; Menezes, Rodrigo Cunha Alvim de; Chianca Júnior, Deoclécio Alves; Braga, Valdir de Andrade; Pedrosa, Maria Lúcia; Bezerra, Frank Silva; Fazan Júnior, Rubens
    Introdução: Insuficiência cardíaca, desregulação autonômica, hipotensão e bradicardia são problemas comuns nos casos de restrição alimentar (RA) severa e é bem estabelecido que o sistema renina angiotensina aldosterona (SRAA) é importante no controle da pressão arterial através da ação sobre vários órgãos. Entretanto pouco se sabe sobre o SRAA e sua influência nas respostas cardiovasculares na RA. Objetivo: Nós avaliamos o efeito da RA na via metabólica da Ang-[1-8] na regulação da pressão arterial para investigar como a RA pode causar hipotensão enquanto simultaneamente aumenta a atividade do sistema nervoso simpático. Metodologia e Resultados: Foram usadas ratas Fischer mantidas em dieta controle (CT), ad libitum, ou RA (60%) por 14 dias. O efeito da Ang-[1-8] sobre a pressão arterial média (PAM) foi menor nos animais com RA mesmo ocorrendo uma ativação maior da via metabólica da Ang-[1-8]. O metabolismo da Ang-[1-10] e seu precursor angiotensinogênio (AGT), foram aumentados pela RA como evidenciado pelo aumento da atividade da enzima conversora de angiotensina (ECA) plasmática e elevada concentração de Ang-[1-8]. Após a infusão de Ang-[1-10], houve também aumento na concentração de AGT e na conversão da Ang-[1-10] para outros metabólitos de angiotensina incluindo Ang-[2-10], Ang-[2-8] e Ang-[3-8]. Embora a Ang-[1-8] causou uma resposta pressora menor na RA, foi encontrado que o RNAm para o receptor AT1 foi aumentado em vasos mesentéricos enquanto nenhuma alteração foi observada na expressão dos receptores AT2 e Mas. Além da expressão, a responsividade do receptor AT1 na RA foi aumentada após infusão de losartan. Entretanto, após infusão de fenilefrina, a amplitude da resposta pressora foi a mesma que a observada no grupo CT. Conclusão: Nossos resultados sugerem que as vias metabólicas da angiotensina estão ativadas constantemente no modelo de RA aumentando a concentração plasmática da Ang-[1-8] e seus peptídeos downstream em compensação a hipotensão, bradicardia e hipovolemia
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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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    Increased α1-adrenoreceptor activity is required to sustain blood pressure in female rats under food restriction.
    (2015) Souza, Aline Maria Arlindo de; Menezes, Rodrigo Cunha Alvim de; Abreu, Aline Rezende Ribeiro de; Araujo, Glaucy Rodrigues de; Costa, Daniela Caldeira; Chianca Júnior, Deoclécio Alves
    Aims: Weevaluated the effect of food restriction (FR) on the various reflexes involved in short termcardiovascular regulation; we also evaluated the contribution of the sympathetic nervous systemand of the plasmatic nitric oxide (NO) in the development of the counterregulatory cardiovascular changes triggered by FR. Main methods: Female rats were subjected to FR for 14 days, and after this period biochemical measurements of biochemical parameterswere performed. For physiological tests, animalswere anaesthetised, and a catheter was inserted into the femoral artery and vein for the acquisition of blood pressure and heart hate, and drug infusion, respectively.We then tested the Bezold–Jarisch reflex, the baroreflex and chemoreflex and the effect of the infusion of adrenergic receptor antagonists in control and food restricted animals. Key findings: The rats subjected to severe FR presented biochemical changes characteristic ofmalnutrition with a great catabolic state. FR also led to hypotension and bradycardia besides reducing the plasmatic concentration of NO. Moreover, activation of the Bezold–Jarisch reflex induced a more pronounced hypotensive response in animals subjected to FR. Intravenous infusion of a α1-adrenoreceptor antagonist induced a greater hypotensive response and a more pronounced tachycardic response in animals under food restriction,while the infusion of β- adrenoreceptor antagonist induced lower increases in blood pressure in these animals. Significance: Our results suggest that an increased α1-adrenoreceptor activity in the resistance arteries coupled with a reduction of plasmatic NO contributes in a complementary manner to maintain the blood pressure levels in animals under FR.
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    Influência da restrição alimentar no controle da pressão arterial sistêmica.
    (Programa de Pós-Graduação em Ciências Biológicas. Núcleo de Pesquisas em Ciências Biológicas, Pró-Reitoria de Pesquisa e Pós Graduação, Universidade Federal de Ouro Preto., 2013) Souza, Aline Maria Arlindo de; Chianca Júnior, Deoclécio Alves; Menezes, Rodrigo Cunha Alvim de
    Anorexia nervosa é caracterizada por alterações psicológicas que ocasionam uma distorção da imagem corporal, um medo extremo de engordar e uma redução voluntária na ingestão alimentar. Esses pacientes muitas vezes desenvolvem alterações cardiovasculares, as quais são consideradas a principal causa de morte. Na impossibilidade de desenvolver experimentos com humanos, modelos experimentais que apresentam alterações semelhantes à anorexia tornam-se necessários para uma melhor compreensão da patologia. O modelo de restrição alimentar (RA) utilizado consiste na redução de 60% da quantidade de micro e macronutrientes oferecidos durante 14 dias. No 14º dia o grupo controle e RA foram subdivididos em três grupos experimentais: central, periférico e dosagens bioquímicas. Após o período de dieta, observamos que a mesma diminuiu o peso corporal dos animais e gerou alterações bioquímicas e fisiológicas semelhantes as que ocorrem na anorexia. As alterações bioquímicas foram diminuição da albumina plasmática, colesterol total e LDL, AST e ureia, juntamente com aumento na concentração de glicose e creatinina. Já as alterações fisiológicas foram anestro, diminuição da pressão arterial média (PAM) e da frequência cardíaca (FC). Também observamos edema cerebral e pulmonar e diminuição no peso do coração, rim e fígado, segundo peso absoluto. Posteriormente, testamos os sistemas que controlam a pressão arterial e a RA diminuiu o óxido nítrico plasmático e ocasionou uma resposta hipotensora maior após estimulação periférica do reflexo Bezold- Jarisch. Esse mesmo perfil de resposta foi observado após inibição periférica dos receptores α1 adrenérgico, porém quando bloqueamos os receptores β adrenérgicos houve uma resposta pressora menor. A infusão de Ang I aumentou mais a PAM nos animais RA, a qual posteriormente foi abolida pelo captopril. Quando colocamos Ang II por via endovenosa ou intracerebroventricular a resposta pressora foi menor na restrição em ambas as vias de administração. No bloqueio dos receptores AT1 centrais houve uma hipotensão mais acentuada que não foi observada no teste periférico e após dosagem da concentração de Ang II plasmática não houve diferença. Contudo, podemos dizer que o protocolo de restrição alimentar foi eficiente em desenvolver alterações bioquímicas e fisiológicas semelhantes as da anorexia nervosa diminuiu a concentração de óxido nítrico plasmático, aumentou a atividade simpática no vaso e aumentou a resposta hipotensora do reflexo Bezold-Jarisch. No sistema renina angiotensina, ocorreu uma resposta pressora reduzida após infusão de Ang II nos animais submetidos à restrição alimentar, também houve um aumento da responsividade após infusão de angiotensina I dependente de ECA juntamente com um aumento da atividade do receptor AT1.
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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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    PLA-PEG nanospheres decorated with phage display selected peptides as biomarkers for detection of human colorectal adenocarcinoma.
    (2020) Souza, Aline Maria Arlindo de; Borges, William de Castro; Andrade, Milton Hércules Guerra de; Maia, Yara Cristina de Paiva; Goulart Filho, Luiz Ricardo; Lanna, Elisa Gomes; Brito, Ana Carolina Ferreira de; Barboza, Ana Paula Moreira; Mosqueira, Vanessa Carla Furtado; Rúbio, Karina Taciana Santos
    Peptide-mediated targeting to colorectal cancer can increase selectivity and specificity of this cancer diagnosis acting as biomarkers. The present work aimed to select peptides using the phage display technique and associate the peptides with polymeric nanospheres in order to evaluate their cytotoxicity and selectivity during cell interaction with Caco-2 human colon tumor cell line. Two peptides identified by phage display (peptide-1 and peptide-2) were synthesized and exhibited purity higher than 84%. Poly(lactic acid)-block-polyethylene glycol nanospheres were prepared by nanoprecipitation and double emulsion methods in order to load the two peptides. Nanoparticles ranged in size from 114 to 150 nm and peptide encapsulation efficiency varied from 16 to 32%, depending on the methodology. No cytotoxic activity was observed towards Caco-2 tumor cell line, either free or loaded peptides in concentrations up to 3 μM at incubation times of 6 and 24 h, indicating safety as biomarkers. Fluorescein isothiocyanate–labeled peptides allowed evaluating selective interactions with Caco-2 cells, where peptide-1 entrapped in nanospheres showed greater intensity of co-localized cell fluorescence, in comparison to peptide-2. Peptide-1 loaded in nanospheres revealed promising to be investigated in further studies of selectivity with other human colon rectal cells as a potential biomarker.
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    Protein restriction after weaning modifies the calcium kinetics and induces cardiomyocyte contractile dysfunction in rats.
    (2013) Penitente, Arlete Rita; Novaes, Rômulo Dias; Chianca Júnior, Deoclécio Alves; Silva, Márcia Ferreira da; Silva, Marcelo Eustáquio; Souza, Aline Maria Arlindo de; Fonseca, Silvia Carolina Guatimosim; Almeida, Pedro William Machado de; Alves, Márcia Netto Magalhães; Felix, Leonardo Bonato; Neves, Clóvis Andrade; Natali, Antônio José
    Protein restriction (PR) is associated with cardiovascular diseases. The purpose of this study was to investigate the effects on single ventricular cardiomyocyte contractile function of a short-term PR after weaning. Male Fischer rats that were 28 days old were randomly divided into a control group (CG, n = 16) and a protein-restricted group (PRG, n = 16). After weaning, CG and PRG animals received isocaloric diets containing 15 and 6% protein, respectively, for 35 days. Biometric parameters were then measured, and the hearts were removed for the analysis of contractile function and calcium transient in isolated cardiomyocytes of the left ventricule (LV), and the quantification of calcium and collagen fibers in LV myocardium. PRG animals had lower body weight (BW) and LV weight (LVW), an increased LVW to BW ratio and a higher proportion of collagen fibers than CG animals. PRG animals exhibited reduced tissue levels of calcium, reduced the length, width and volume of cardiomyocytes and their sarcomere length compared to CG animals. Cardiomyocytes from PRG animals had a lower amplitude of shortening, a slower time to the peak of shortening and a longer time to half-relaxation than those from the CG. Cardiomyocytes from PRG animals also presented a lower peak of calcium transient and a longer calcium transient decay time than CG animals. Taken together, the results indicate that short-term PR after weaning induces a marked structural remodeling of the myocardium parenchyma and stroma that coexists with contractile dysfunctions in single LV cardiomyocytes of rats, which is probably associated with pathological changes of the intracellular calcium kinetics, rather than inadequate available amounts of this mineral in cardiac tissue.
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    Role of the renin angiotensin system in blood pressure allostasis-induced by severe food restriction in female Fischer rats.
    (2018) Souza, Aline Maria Arlindo de; West, Crystal A.; Abreu, Aline Rezende Ribeiro de; Pai, Amrita V.; Mesquita, Laura Batista Tavares; Ji, Hong; Chianca Júnior, Deoclécio Alves; Menezes, Rodrigo Cunha Alvim de; Sandberg, Kathryn
    Severe food restriction (FR) is associated with blood pressure (BP) and cardiovascular dysfunction. The renin-angiotensin system (RAS) regulates BP and its dysregulation contributes to impaired cardiovascular function. Female Fischer rats were maintained on a control (CT) or severe FR (40% of CT) diet for 14 days. In response to severe FR, BP allostasis was achieved by up-regulating circulating Ang-[1–8] by 1.3-fold through increased angiotensin converting enzyme (ACE) activity and by increasing the expression of AT1Rs 1.7-fold in mesenteric vessels. Activation of the RAS countered the depressor effect of the severe plasma volume reduction (≥30%). The RAS, however, still underperformed as evidenced by reduced pressor responses to Ang-[1–8] even though AT1Rs were still responsive to the depressor effects of an AT1R antagonist. The aldosterone (ALDO) response was also inadequate as no changes in plasma ALDO were observed after the large fall in plasma volume. These findings have implications for individuals who have experienced a period(s) of severe FR (e.g., anorexia nervosa, dieters, natural disasters) and suggests increased activity of the RAS in order to achieve allostasis contributes to the cardiovascular dysfunction associated with inadequate food intake.
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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.