Publications by authors named "Mariana Severo da Costa"

8 Publications

  • Page 1 of 1

Prenatal stress and KCl-induced depolarization modulate cell death, hypothalamic-pituitary-adrenal axis genes, oxidative and inflammatory response in primary cortical neurons.

Neurochem Int 2021 Jul 5;147:105053. Epub 2021 May 5.

Laboratory of Pediatric Physical Activity, Infant Center, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Laboratory of Cellular Biophysics and Inflammation, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. Electronic address:

Maternal stress has been described as an important component in the offspring's cerebral development, altering the susceptibility to diseases in later life. Moreover, the postnatal period is essential for the development and integration of several peripheral and central systems related to the control of homeostasis. Thus, this study aimed to evaluate the effects of prenatal stress on the activation of cortical neurons, by performing experiments both under basal conditions and after KCl-induced depolarization. Female mice were divided in two groups: control and prenatal restraint stress. Cortical neurons from the offspring were obtained at gestational day 18. The effects of prenatal stress and KCl stimulations on cellular mortality, autophagy, gene expression, oxidative stress, and inflammation were evaluated. We found that neurons from PNS mice have decreased necrosis and autophagy after depolarization. Moreover, prenatal stress modulated the HPA axis, as observed by the increased GR and decreased 5HTr1 mRNA expression. The BDNF is an important factor for neuronal function and results demonstrated that KCl-induced depolarization increased the gene expression of BDNF I, BDNF IV, and TRκB. Furthermore, prenatal stress and KCl treatment induced significant alterations in oxidative and inflammatory markers. In conclusion, prenatal stress and stimulation with KCl may influence several markers related to neurodevelopment in cortical neurons from neonate mice, supporting the well-known long-term effects of maternal stress.
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http://dx.doi.org/10.1016/j.neuint.2021.105053DOI Listing
July 2021

Effects of running before pregnancy on long-term memory and hippocampal alterations induced by prenatal stress.

Neurosci Lett 2021 02 19;746:135659. Epub 2021 Jan 19.

Laboratory of Pediatric Physical Activity, Infant Center, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Laboratory of Cellular Biophysics and Inflammation, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. Electronic address:

Studies have shown that an adverse environment in utero influences fetal growth and development, leading to several neuroendocrine and behavioral changes in adult life. Nevertheless, the mechanisms involved in the long-term benefits of pregestational exercise are still poorly understood. Thus, this study aimed to evaluate the effects of physical exercise before the gestational period on memory behavior and gene expression in the hippocampus of adult mice submitted to prenatal stress. Female Balb/c mice were divided into three groups: control (CON), prenatal restraint stress (PNS), and exercise before the gestational period plus PNS (EX + PNS). When adults, male and female offspring were submitted to the object recognition test followed by the hippocampal evaluation of BDNF exons I and IV mRNA expression, as well as hypothalamic-pituitary-adrenal axis related genes. Pregestational exercise did not prevent the decreased recognition index, as well as GR and CRHR1 gene expression observed in PNS males. Conversely, prenatal stress did not influence female memory behavior. Moreover, exercise attenuated the effects of prenatal stress on female BDNF IV gene expression. The results indicate that pregestational exercise was able to prevent the effects of maternal stress on hippocampal BDNF IV gene expression in females, although no effects were seen on the stress-induced memory impairment in males.
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http://dx.doi.org/10.1016/j.neulet.2021.135659DOI Listing
February 2021

Anti-inflammatory effect of octyl gallate in alveolar macrophages cells and mice with acute lung injury.

J Cell Physiol 2020 09 22;235(9):6073-6084. Epub 2020 Jan 22.

Laboratório de Pesquisa em Biofísica Celular e Inflamação, Departamento de Biologia Celular e Molecular, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.

Acute lung injury (ALI) is an inflammatory process, and has high incidence and mortality. ALI and the acute respiratory distress syndrome are two common complications worldwide that result in acute lung failure, sepsis, and death. Pro-inflammatory substances, such as cytokines and chemokines, are responsible for activating the body's defense mechanisms and usually mediate inflammatory processes. Therefore, the research of substances that decrease the uncontrolled response of organism is seen as potential for patients with ALI. Octyl gallate (OG) is a phenolic compound with therapeutic actions namely antimicrobial, antiviral, and antifungal. In this study, we evaluated its action on lipopolysaccharide (LPS)-activated alveolar macrophages RAW 264.7 cells and ALI in male mice. Our results demonstrated protective effects of OG in alveolar macrophages activated with LPS and mice with ALI. The OG treatment significantly decreased the inflammatory markers in both studies in vitro and in vivo. The data suggested that OG can act as an anti-inflammatory agent for ALI.
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http://dx.doi.org/10.1002/jcp.29536DOI Listing
September 2020

Exercise before pregnancy attenuates the effects of prenatal stress in adult mice in a sex-dependent manner.

Int J Dev Neurosci 2020 Apr 5;80(2):86-95. Epub 2020 Feb 5.

Laboratory of Pediatric Physical Activity, Infant Center, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.

The present study aimed to investigate the long-term effects of exercise before pregnancy on changes induced by prenatal stress. Female and male Balb/c mice were divided into three groups: control (CON), prenatal restraint stress (PNS), and exercise before the gestational period plus PNS (EX + PNS). As adult, fear/anxiety behavior, corticosterone secretion, expression of hypothalamic-pituitary-adrenal (HPA)-related genes, as well as epigenetic modifications were evaluated. Exercise before gestation did not prevent the increased fear/anxiety behavior in PNS mice. A nearly significant (p = .06) basal corticosterone increase was observed in PNS males and the exercise before pregnancy reduced the stress-induced corticosterone increase in PNS females. In addition, an increase on prefrontal cortex (PFC) CRHR1 gene expression was observed in PNS females, which was attenuated by the exercise before gestation. We have also found a glucocorticoid receptor (GR) gene expression decrease in the prefrontal cortex in PNS males, as well as a histone H3 acetylation decrease (p = .06) close to the significance level. In conclusion, pregestational exercise may attenuate developmental changes induced by prenatal stress in a sex-dependent manner.
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http://dx.doi.org/10.1002/jdn.10001DOI Listing
April 2020

Sex differences in the effects of acute stress on cerebral glucose metabolism: A microPET study.

Brain Res 2019 11 26;1722:146355. Epub 2019 Jul 26.

Infant Center, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS 90619-900, Brazil. Electronic address:

Stress has been considered as a risk factor for the development and aggravation of several diseases. The hypothalamic-pituitary-adrenal axis (HPA) is one of the main actors for the stress response and homeostasis maintenance. Positron emission tomography (PET) has been used to evaluate neuronal activity and to study brain regions that may be related to the HPA axis response. Since neuroimaging is an important tool in detecting neuroendocrine-related changes, we used fluorodeoxyglucose-18 (F-FDG) and positron emission microtomography (microPET) to evaluate sexual differences in the glucose brain metabolism after 10, 30 and 40 min of acute stress in Balb/c mice. We also investigated the effects of restraint stress in blood, liver and adrenal gland F-FDG biodistribution using a gamma counter. A decreased glucose uptake in the whole brain in both females and males was found. Additionally, there were time and sex-dependent alterations in the F-FDG uptake after restraint stress in specific brain regions, indicating that males could be more vulnerable to the short-term effects of acute stress. According to the gamma counter biodistribution, only females showed a significant decreased glucose uptake in the blood, liver and right adrenal after restraint stress. In addition, in comparisons between the sexes, males showed a decreased glucose uptake in the whole brain and in several brain regions compared to females. In conclusion, exposure to acute restraint stress resulted in significant decreased glucose metabolism in the brain, with particular effects in different regions and organs in a sex-specific manner.
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http://dx.doi.org/10.1016/j.brainres.2019.146355DOI Listing
November 2019

Cholinergic anti-inflammatory pathway confers airway protection against oxidative damage and attenuates inflammation in an allergic asthma model.

J Cell Physiol 2020 02 22;235(2):1838-1849. Epub 2019 Jul 22.

Laboratory of Pediatric Respirology, Infant Center, Pontifícia Universidade Católica do Rio Grande do Sul, PUCRS, Hospital Moinhos de Vento, HMV, Porto Alegre, Brazil.

Asthma is characterized by the influx of inflammatory cells, especially of eosinophils as well as reactive oxygen species (ROS) production, driven by the release of the T helper 2 (Th2)-cell-associated cytokines. The cholinergic anti-inflammatory pathway (CAP) inhibit cytokines production and controls inflammation. Thus, we investigated the effects of pharmacological activation of CAP by neostigmine on oxidative stress and airway inflammation in an allergic asthma model. After the OVA challenge, mice were treated with neostigmine. We showed that CAP activation by neostigmine reduced the levels of pro-inflammatory cytokines (IL-4, IL-5, IL-13, IL-1β, and TNF-α), which resulted in a decrease of eosinophils influx. Furthermore, neostigmine also conferred airway protection against oxidative stress, attenuating ROS production through the increase of antioxidant defense, evidenced by the catalase (CAT) activity. We propose, for the first time, that pharmacological activation of the CAP can lead to new possibilities in the therapeutic management of allergic asthma.
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http://dx.doi.org/10.1002/jcp.29101DOI Listing
February 2020

Autophagy induces eosinophil extracellular traps formation and allergic airway inflammation in a murine asthma model.

J Cell Physiol 2020 01 17;235(1):267-280. Epub 2019 Jun 17.

Laboratory of Pediatric Respirology, Infant Center, School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.

Studies have shown autophagy participation in the immunopathology of inflammatory diseases. However, autophagy role in asthma and in eosinophil extracellular traps (EETs) release is poorly understood. Here, we attempted to investigate the autophagy involvement in EETs release and in lung inflammation in an experimental asthma model. Mice were sensitized with ovalbumin (OVA), followed by OVA challenge. Before the challenge with OVA, mice were treated with an autophagy inhibitor, 3-methyladenine (3-MA). We showed that 3-MA treatment decreases the number of eosinophils, eosinophil peroxidase (EPO) activity, goblet cells hyperplasia, proinflammatory cytokines, and nuclear factor kappa B (NFκB) p65 immunocontent in the lung. Moreover, 3-MA was able to improve oxidative stress, mitochondrial energy metabolism, and Na , K -ATPase activity. We demonstrated that treatment with autophagy inhibitor 3-MA reduced EETs formation in the airway. On the basis of our results, 3-MA treatment can be an interesting alternative for reducing lung inflammation, oxidative stress, mitochondrial damage, and EETs formation in asthma.
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http://dx.doi.org/10.1002/jcp.28966DOI Listing
January 2020

Reactive oxygen species are involved in eosinophil extracellular traps release and in airway inflammation in asthma.

J Cell Physiol 2019 12 10;234(12):23633-23646. Epub 2019 Jun 10.

Laboratory of Pediatric Respirology, Infant Center, Medicine School, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.

In asthma, there are high levels of inflammatory mediators, reactive oxygen species (ROS), and eosinophil extracellular traps (EETs) formation in airway. Here, we attempted to investigate the ROS involvement in EETs release and airway inflammation in OVA-challenged mice. Before the intranasal challenge with ovalbumin (OVA), animals were treated with two ROS inhibitors, N-acetylcysteine (NAC) or diphenyleneiodonium (DPI). We showed that NAC treatment reduced inflammatory cells in lung. DPI and NAC treatments reduced eosinophil peroxidase (EPO), goblet cells hyperplasia, proinflammatory cytokines, NFκB p65 immunocontent, and oxidative stress in lung. However, only the NAC treatment improved mitochondrial energy metabolism. Moreover, the treatments with DPI and NAC reduced EETs release in airway. This is the first study to show that ROS are needed for EETs formation in asthma. Based on our results, NAC and DPI treatments can be an interesting alternative for reducing airway inflammation, mitochondrial damage, and EETs release in asthma.
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http://dx.doi.org/10.1002/jcp.28931DOI Listing
December 2019