Grants and Projects
Gene-environment interactions in COCCaINE Use Disorder: Collaborative Case-Control Initiative in Coccaine Addiction
NIH/NIDA - GLOBAL BRAIN AND NERVOUS SYSTEM DISORDERS RESEARCH ACROSS THE LIFESPAN (R01) - 1 R01 DA044859-01 (Grassi-Oliveira, PI; Schmitz, PI; Walss-Bass, PI) Current - 2017/09/20
The aim of this new application is to examine genome- wide associations with cocaine use disorder and to characterize the role of environmental stressors such as trauma and HIV infection on epigenetic signatures and gene-environment interactions with cocaine addiction severity in Brazil. A part of the project is also dedicated to enhancing research capacity and infrastructure related to cocaine use disorder research in Rio Grande do Sul, Brazil. The identification of factors predisposing to cocaine addiction is highly significant, as it can lead to personalized prevention and treatment. The scientific premise is solidly supported by literature, preliminary data show the DNA is of good-quality and the cohort is well-characterized. The rigor is supported by large group numbers and a plan for replication of the findings. The investigators are qualified, have a history of collaboration, and will build the research capacity building through training and workshops an important aspect of the project. That said, the project seems somewhat overambitious, overly focused on correlations while the bioinformatics part is underdeveloped. Most importantly, HIV positivity may overshadow any trauma effects, and the bioethical aspects and possibly legal aspects of genetic research, not just for this project, but as a component of the research capacity in Brazil, are not addressed. Taken in balance the strengths outweighed the weaknesses panel expressed high enthusiasm for this promising project.
Targets for Protection of Women Crack Users: Early Victimization, Oxytocin and Cognition
CNPq/SENAD Neuropsychiatric Disorders and Drug Treatments – 4668002/2014-5 (Grassi-Oliveira, PI) Current - 2015/10/13
Oxytocin (OC) is a neuropeptide with regulatory properties of neurotransmitter systems, and changes in its signaling are related to a range of impairments in psychosocial and cognitive functioning. Considering that female crack users are marked by a history of victimization and that they have psychosocial changes related to changes in OC signaling, this project aims to investigate targets for protection of female crack users. Three studies are planned in order to cope with our aims. Study 1 we will investigate groups of women crack users (n = 40), men crack users (n = 40) and groups of healthy men (n = 40) and women (n = 40). Psychiatric symptoms, history of victimization and cognitive performance will be investigated. OC plasma concentration and methylation of OXTR will be assessed. In Study 2 we will follow a group of female crack users (n = 85) during the detoxification period (21 days). We will investigate, in three different moments, changes in OC signaling, in psychiatric symptoms and in cognitive performance. The history of victimization and the psychosocial functioning of the participants will also be investigated. In Study 3 we will investigate the action of intranasal OC in the neurofunctional response during exposure to drug-related stimuli, and functional connectivity after exposure to drug-related stimuli in female crack users. A placebo-controlled clinical-trial will be held up with 40 female crack users and 40 healthy women.
MicroRNAs related to neuroinflammation in mice exposed to maternal separation and cocaine
CNPq UNIVERSAL/Science Without Borders – 454429/2014-2 // 454429/2014-2 (Grassi-Oliveira, PI) Current - 2014/06/16
No study sought to investigate the relationship between early life stress, cocaine dependence and the role of miRNAs
related to inflammatory process. Thus, the aim of this research is to investigate the impact of maternal separation in the expression of miRNAs related to inflammatory response and brain plasticity in mice and its association with cocaine CPP during adolescence.
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Epigenetics and Molecular Mechanisms of Developmental Stress
Neurobiology of Early Life Stress and Mental Disorders
Trauma, Stress and Development: Cognitive and Behavioral Process in Mental Disorders
We Work Hard But Party Harder
Prof. Rodrigo Grassi-Oliveira, M.Sc., M.D., Ph.D
I am Professor of Psychiatry and Research Neuroscientist at Brain Institute, PUCRS. All my efforts have been done to understand if neuroimmune pathways related to brain plasticity and brain development can be harnessed to reverse the deleterious effects of early life adversities before they reach clinical significance, particularly regarding reward system. I'm always craving for traveling, movies, diving and cooking.
Thiago Wendt Viola, M.Sc., Ph.D
Postdoctoral Research Scientist and Lab Manager
Thiago has a master's and a PhD in Pediatrics and Health Sciences with a focus on Neuroscience. At DCNL his focus is to study the effects of ELS on epigenetic mechanism in both human and mice models. He is supervisor of graduate students at the Postgraduate Program in Medicine - Neuroscience and Postgraduate Program in Pediatrics at PUCRS. Outside the lab he really like to hangout with friends and watch Netflix.
Aline Zaparte, M.Sc., Ph.D
Postdoctoral Research Scientist
She received her bachelor’s degree in Biomedical Sciences, her master’s degree in Cellular and Molecular biology and her PhD in Health Sciences from PUCRS. She is the manager of the wet lab, responsible for biological sample collection and bench experiments. Currently, her research has focused on investigating how substance use can affect the immune system and the interaction of crack cocaine with HIV infection. Outside the lab, she enjoys travelling and explore new places with good food, drinks and music.
Luis Eduardo Wearick-Silva, M.Sc. Ph.D
Posdoctoral Research Scientist
Luis graduated with a bachelor's degree in Physical Education from the Pontifical Catholic University of Rio Grande do Sul in 2013. During most of his graduate studies, he worked in several animal studies at DCNL investigating the impact of early-life stress on learning and memory. Additionaly, is mainly interested in the neurobiology of exercise, studying if physical exercise can mitigate the consequences of early-life stress.
Bruno Kluwe-Schiavon, M.Sc. Ph.D
Posdoctoral Research Scientist
Bruno is a certified cognitive-behaviour therapist with experience in decision-making behaviours and cognitive sciences who studied psychology at the Pontifical Catholic University of Rio Grande do Sul (PUCRS) and finished his PhD at the University of Zurich, Switzerland (UZH). His ultimate research goal is to unveil how biopsychosocial factors shape individual information processing and the likelihood of engaging in risky behaviours. As a side personal project, Bruno enjoys reading and writing about the concepts of freedom and free-will.
Medicine and Health Sciences - Neurosciences
Anderson has a degree in Biology from PUCRS. In DCNL, his focus is to study the effects of ELS and addiction in mice, in order to understand the molecular mechanisms and behavioral changes that lead individuals exposed to early life stress to be more vulnerable substance use disorders. Outside the lab, he enjoys studying about climate change, environmental education and running around the city.
Lucas Poitevin Bandinelli
Lucas graduated in Psychology at PUCRS in 2012 and has been working as clinical psychologist. At DCNL his focus is to investigate the impact of stress on psychosocial factors, the development of psychopathologies and their interaction within the context of health and disease, particularly breast cancer. In his free time, he enjoys running, traveling and playing the guitar.
Pediatrics and Child Health
Rodrigo graduated with a bachelor's degree in Physical Therapy from the Pontifical Catholic University of Rio Grande do Sul in 2017. During most of his undergraduate studies, he worked as a research assistant in several animal studies at DCNL. Now as a PhD student his main interest is to investigate the impact of early life stress on cognitive performance and its underlying mechanisms in rodents. Outside of the lab he enjoys spending time with friends and watching soccer.
Saulo Gantes Tractenberg
Saulo is a psychologist graduated from the Pontifical Catholic University of Rio Grande do Sul (PUCRS). His interest is to investigate the effects of ELS during sensitive periods of neurodevelopment as potential risk factors for psychopatology. Specifically, he are focused on explore the basis for resilience and vulnerability to stress response in a translational perspective. Outside the work, he is an American Sports fan, following all about NFL and his team New York Giants. He likes to travel around the world and explore new cultures.
Psychiatrist with extensive experience in the treatment of addictive disorders and cognitive behavioral therapy. Master student in Psychology at the Pontifical Catholic University (PUCRS). At DCNL herfocus of interest is the variation of craving for different drugs during detoxification of crack cocaine hospitalized women. Her leisure activities are creating her own clothes, meeting friends, exercising, gardening, and traveling.
João Paulo Ottolia Niederauer
João graduated from the Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil, with a Psychology major in 2018. At DCNL his project focus to study the interaction between HIV and miRNAs in a population with crack-cocaine substance use disorder. Outside of the lab he enjoys traveling, watch movies, play and watch sports and play videogames.
João Vítor Nóbrega
Medicine and Health Sciences - Neurosciences
Graduated from Medical School in 2013 and completed Psychiatry Residency in 2018. Master’s student of Medicine and Health Sciences from PUCRS, with emphasis in Neurosciences. Researching the effects of Oxytocin on behavioural and cognitive impairments related to cocaine withdrawal in women. In his free time, enjoys watching films, listening to music, cooking and jamming on guitar with friends.
Augusto Martins Lucas Bittencourt
Master Student (candidate)
Augusto is a psychiatrist studying the effects of early life stress on neurostructural parameters in Magnetic Ressonance Imaging of crack-cocaine users.
Bernardo Aguzzoli Heberle
Bernardo graduated from the University of Kentucky with a Neurosciences major in 2019. At DCNL his focus is to study the effects of ELS on a mouse model of opioid withdrawal. Outside of the lab he enjoys playing basketball, lifting weights, and traveling.
Amanda Stephanie Beidacki
She is undergrad in Biomedical Sciences at PUCRS. She is working mainly with human blood sample collection and PBMCs isolation. Her research interest is to understand the influence of crack cocaine use on immune system. Outside the lab, she enjoys playing violin and traveling.
Bernardo Paim de Mattos
Bernardo is a psychology undergraduate student from PUCRS University . At DCNL, his focus is to study social vulnerability markers within crack-cocaine abusers, such as imprisonment. Other than working with us he also loves reading, rap music and powerlifting.
Érika Kestering Ferreira
Érika is an undergraduate psychology student hoping to get her major by the end of 2021 from the Pontifical University of Rio Grande do Sul (PUCRS). She has been research assistant at DCNL since 2017 and her focus is to study the effects of early life stress on experimental models, currently working in a mice model of opioid withdrawal. Outside of the lab she likes to enjoy her afternoons walking and reading in parks and meeting her friends for food and drinks.
Francisco Sindermann Lumertz
Francisco is a psychology undergraduate sutudent at the Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS). At DCNL, he studies the impact of early life stress on cognition of mice exposed to neonatal hypoxia-ischemia. On his free time, he enjoys palying basketball, listening to podcasts and spending time with his friends.
Gisele Iesbich Vargas
Gisele is an undergraduate student in psychology course. At DCNL, works as research assistant and her main function is collecting clinical data from research volunteers. Has special interest in the impact of drug abuse on human cognition.
Julia de Bittencourt Torres
Julia is a psychology student at PUCRS. At DCNL, her focus is on clinical research and studies with crack / cocaine-dependent users and their effects. At leisure, Julia enjoys horse riding and spending time with her horse and dog, family and friends.
Leonardo Melo Rothmann
Leonardo is a psychology student at PURS. At DCNL his focus is to study the effects of early life stress and the biopsychosocial impact that drug use has on users, especially crack-cocaine users. Outside the lab he enjoys traveling, listening to music, and hanging out with friends.
Lucca Pizzato Tondo
Lucca is a medical student at PUCRS, graduating in 2022. At DCNL, he studies the neuroimaging changes in drug addiction. Besides hacking brains in the lab, he also loves playing music and fighting judo.
Luiza is a undergrad student in psychology course at Pontíficia Universidade Católica do Rio Grande do Sul (PUCRS). At DCNL, she participates in clinical research with people who have substance use disorders. Has special interest in studying trauma and substance use disorders. In her free time, she likes to spend time with her friends and her family.
Luiza Martins Costa Malcon
Luiza is currently taking her bachelor degree in Psychology. She has been in DCNL since 2016, and has studied the effects of ELS on anxiety and oxidative stress in mice. Her current focus of study is the effects of ELS in cocaine addiction and she has a particular interest in sex differences. She interns at a psychological assessment clinic, and outside the lab she enjoys spending time with her friends and traveling.
Marco Giovanni Signor Gomes
Marco is a student of Medicine at PUCRS since 2017, intending to be a pediatrician or an obstetrician. At DCNL is focused to study the impact of ELS on cognitive development, aiming for analysis of behavior and neuronal microscopic modification during development. Outside of the lab he enjoys swimming, surfing and playing piano.
Rafael Brunstein Genovese
Rafael is a undergraduated student of PUCRS school of medicine with interests in psychiatry and neurology.At DCNL his focusis to study the effect of cocaine use in the structure of the brain rescherching that with neuroimaging (more specifically with DTI techniques). Outside the lab he enjoys a lot of sports (soccer, footbol and basketball) and weight lifting.
Renata do Amaral Martins
Renata is a medical student at Pontifícia Universidade Católica do Rio Grande do Sul. At DCNL her focus is to study the correlation between drug addition and early stress in life. Outside of the lab she enjoys dancing and traveling.
Viola, T.W., L.E. Wearick-Silva, K.C. Creutzberg, E. Kestering-Ferreira, R. Orso, A. Centeno-Silva, L. Albrechet- Souza, P.R. Marshall, X. Li, T.W. Bredy, M.A. Riva, and R. Grassi-Oliveira. Psychoneuroendocrinology, 2019. 99: p. 8-19
Postnatal impoverished housing impairs adolescent risk-assessment and increases risk-taking: A sex-specific effect associated with histone epigenetic regulation of Crfr1 in the medial prefrontal cortex.
While increasing evidence posits poor decision-making as a central feature of mental disorders, very few studies investigated the effects of early-life stress (ELS) on specific components of reward-related choice behaviors. Risk-taking (RT) involves the exposure to some danger, or negative consequences, in order to achieve a goal-directed behavior. Such behaviors are likely to be preceded by risk-assessment (RA), which is a dynamic cognitive process involving the acquisition of information in potentially dangerous situations. Here, we investigated the effects of being raised in impoverished housing conditions during early life (P2–P9) on RT, RA and dopaminergic and corticotrophinergic gene expression of adolescent male and female mice. Phenotypes were assessed by two protocols: the elevated plus-maze (EPM) and the predator-odor risk-taking (PORT). We found decreased RA in mice exposed to impoverished housing in the absence of a reward (EPM), with a more pronounced effect among females. Moreover, when exposed to a predatory olfactory cue, increased RT was observed in these females in a reward-related task (PORT), as well as decreased HPA axis responsivity. This sex-specific behavioral effect was associated with increased Crfr1 mRNA expression in the medial prefrontal cortex (mPFC) and higher levels of the histone mark H3R2me2s, a histone modification known to be involved in transcriptional activation, within the promoter of the Crfr1 gene. These findings revealed that ELS exposure can impair the acquisition of environmental information in dangerous situations and increase RT in reward-related scenarios among females, with an important role regarding epigenetic regulation of the Crfr1 gene.
Orso R, Creutzberg KC, Wearick-Silva LE, Wendt Viola T, Tractenberg SG, Benetti F, Grassi-Oliveira R. Front Behav Neurosci. 2019;13:197. doi: 10.3389/fnbeh.2019.00197. eCollection 2019
How Early Life Stress Impact Maternal Care: A Systematic Review of Rodent Studies.
Background: Maternal care refers to the behavior performed by the dam to nourish and protect her litter during its early development. Frequent and high-quality performance of such maternal behaviors is critical for the neurodevelopment of the pups. Maternal exposure to stress during early development can impair maternal care and amplify the deleterious effects of poor maternal caregiving and neglect. As such, a thorough understanding of the effects caused by several models of early life stress on maternal care may yield more insights into the relationship between stress and maternal. behavior. Methods: A systematic review was performed to identify and address the effects of early life stress on maternal behavior. The search was conducted using three online databases: PUBMED, Embase, and Web of Science. To provide clear evidence of the impact of stress on maternal care, in every study, the stress group was always compared to a control group. Outcomes were categorized into eight different behaviors: (1) licking/grooming; (2) arched-back nursing; (3) blanket-nursing/passive nursing; (4) nest building; (5) contact with pups; (6) harmful/adverse caregiving; (7) no contact; (8) nest exits. Additionally, the methodological quality of the studies was evaluated. Results: A total of 12 different early life stress protocols were identified from the 56 studies included in this systematic review. Our data demonstrate that different stress models can promote specific maternal patterns of behavior. Regarding the maternal separation protocol, we observed an overall increase in nursing and licking/grooming behaviors, which are essential for pup development. An increase in the number of nest exits, which represents a fragmentation of maternal care, was observed in the limited bedding protocol, but the total amount of maternal care appears to remain similar between groups. Conclusions: Each stress protocol has unique characteristics that increase the difficulty of rendering comparisons of maternal behavior. The increase in maternal care observed in the maternal separation protocol may be an attempt to overcompensate for the time off-nest. Fragmented maternal care is a key component of the limited bedding protocol. Moreover, the methodological approaches to evaluate maternal behavior, such as time, duration, and behavior type should be more homogeneous across studies.
do Prado, C.H., R. Grassi-Oliveira, L. Daruy-Filho, A. Wieck, and M.E. Bauer. Neuropsychopharmacology, 2017. 42(11): p. 2272-2282
Evidence for Immune Activation and Resistance to Glucocorticoids Following Childhood Maltreatment in Adolescents Without Psychopathology.
Early-life stress (ELS) increases the risk for psychopathology. Immune and endocrine changes have been reported in adults and are associated with maladaptation of stress-responsive systems. Here we investigated the effects of ELS on endocrine and immune pathways in adolescents without psychopathology. Thirty adolescents with a history of childhood maltreatment and 27 adolescents without ELS history were recruited. Blood and hair samples were obtained from all participants. Lymphocytes were isolated and stimulated in vitro. Flow cytometry was used to evaluate lymphocyte subsets, Th1/Th2/Th17 cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor kappa B (NF-κB) signaling pathways, as well as lymphocyte sensitivity to dexamethasone. Brain-derived neurotrophic factor (BDNF) and hair cortisol were assessed with enzyme-linked immunosorbent assays (ELISAs). Adolescents with a history of ELS had increased percentages of T-cell activation markers (CD3+CD4+CD25+ and CD3+CD69+) and senescent T cells (CD8+CD28- and CD4+CD28-), as well as decreased percentages of NK (CD3-CD56+) and NK T cells (CD3+CD56+). Following stimulation, lymphocytes of ELS+ adolescents produced significantly more IL-2, IL-4, IFN-γ, and IL-17 and engaged more MAPK ERK and NF-κB signaling. ELS was associated with increased hair cortisol levels in parallel with increased lymphocyte resistance to dexamethasone and low plasma BDNF levels. These data provide the first indication of the presence of immune activation and pro-inflammatory profiles in healthy adolescents exposed to ELS, which could contribute to increased vulnerability of trauma-related psychopathology later in life. The underlying mechanisms of this impairment may include the enhanced activation of both MAPK and NF-κB signaling in parallel to partial resistance to glucocorticoids.
Tractenberg, S.G., M.L. Levandowski, L.A. de Azeredo, R. Orso, L.G. Roithmann, E.S. Hoffmann, H. Brenhouse, and R. Grassi-Oliveira. Neuroscience and Biobehavioral Reviews, 2016. 68: p. 489-503.
An overview of maternal separation effects on behavioural outcomes in mice: Evidence from a four-stage methodological systematic review.
Early life stress (ELS) developmental effects have been widely studied by preclinical researchers. Despite the growing body of evidence from ELS models, such as the maternal separation paradigm, the reported results have marked inconsistencies. The maternal separation model has several methodological pitfalls that could influence the reliability of its results. Here, we critically review 94 mice studies that addressed the effects of maternal separation on behavioural outcomes. We also discuss methodological issues related to the heterogeneity of separation protocols and the quality of reporting methods. Our findings indicate a lack of consistency in maternal separation effects: major studies of behavioural and biological phenotypes failed to find significant deleterious effects. Furthermore, we identified several specific variations in separation methodological procedures. These methodological variations could contribute to the inconsistency of maternal separation effects by producing different degrees of stress exposure in maternal separation-reared pups. These methodological problems, together with insufficient reporting, might lead to inaccurate and unreliable effect estimates in maternal separation studies.