RESUMO
Adeno-associated viruses (AAV) are commonly used in the scientific field due to their diverse application range. However, AAV shedding, the release of virions from the host organism, can impact the safety of AAV-based approaches. An increasing number of authorities require the characterization of vector shedding in clinical trials. Recently, shedding of transduced laboratory animals has also gained attention regarding the necessary disposal measures of their waste products. However, no explicit international regulations for AAV-shedding waste exist. Generating insights into shedding dynamics becomes increasingly relevant to help authorities develop adequate regulations. To date, knowledge of AAV vector shedding in mice is very limited. Moreover, confirmation of functional shed AAV particles in mice is missing. Therefore, we examined feces, urine, and saliva of mice after CNS injection with AAV2/8. It revealed the presence of viral DNA fragments via qPCR for up to 4 days after injection. To examine AAV functionality we performed nested PCR and could not detect full-length viral genomes in any but two collected feces samples. Furthermore, a functional infection assay did not reveal evidence of intact AAV particles. Our findings are supposed to contribute murine shedding data as a foundation to help establish still lacking adequate biosafety regulations in the context of AAV shedding.
Assuntos
DNA Viral , Dependovirus , Vetores Genéticos , Eliminação de Partículas Virais , Animais , Dependovirus/genética , Camundongos , Vetores Genéticos/genética , Vetores Genéticos/administração & dosagem , DNA Viral/genética , Fezes/virologia , Camundongos Endogâmicos C57BL , Saliva/virologia , HumanosRESUMO
Driving under the influence of cannabis (DUIC) is increasing worldwide, and cannabis is the most prevalent drug after alcohol in impaired driving cases, emphasizing the need for a reliable traffic enforcement strategy. ∆9 -tetrahydrocannabinol (THC) detection in oral fluid has great potential for identifying recent cannabis use; however, additional data are needed on the sensitivities, specificities, and efficiencies of different oral fluid devices for detecting cannabinoids at the roadside by police during routine traffic safety enforcement efforts. At the roadside, 8945 oral fluid THC screening tests were performed with four devices: AquilaScan®, Dräger DrugTest®, WipeAlyser Reader®, and Druglizer®. A total of 530 samples screened positive for THC (5.9%) and were analyzed by liquid chromatography-tandem mass spectrometry at multiple cutoff concentrations (2 ng/mL, 10 ng/mL, and manufacturers' recommended device cutoffs) to investigate device performance. Results varied substantially, with sensitivities of 0%-96.8%, specificities of 89.8%-98.5%, and efficiencies of 84.3%-97.8%. The Dräger DrugTest® outperformed the other devices with a 96.8% sensitivity, 97.1% specificity, and 97.0% efficiency at a 5-ng/mL LC-MS/MS confirmation cutoff. The WipeAlyser Reader® had good performance with a 91.4% sensitivity, 97.2% specificity, and 96.4% efficiency. AquilaScan® and Druglizer® had unacceptable performance for cannabinoid detection, highlighted by sensitivity <13%. The choice of roadside oral fluid testing device must offer good analytical performance for cannabinoids because of its high prevalence of use and impact on road safety.
RESUMO
BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with severe social communication, interaction, and sensory processing impairments. Efforts to understand its etiology and pathophysiology are crucial for improving treatment and prevention measures. Preclinical models of ASD are essential for investigating the biological mechanisms and should present translatability potential. We aim to evaluate the consistency of the most commonly used rodent models of ASD in displaying autistic-like behavior through a systematic review and meta-analysis. METHODS: This review will focus on the most frequently used autism models, surveying studies of six genetic (Ube3a, Pten, Nlgn3, Shank3, Mecp2, and Fmr1), three chemically induced (valproic acid (VPA), lipopolysaccharide (LPS), and polyinosinic:polycytidylic acid (poly(I:C))), and one inbred model (BTBR T+ Itpr3tf/J mouse strain). Two independent reviewers will screen the records. Data extraction of behavioral outcomes and risk of bias evaluation will be performed. We will conduct a meta-analysis whenever at least five studies investigate the same model and behavioral outcome. We will also explore the heterogeneity and publication bias. Network meta-analyses are planned to compare different models. DISCUSSION: By shortening the gap between animal behavior and human endophenotypes or specific clinical symptoms, we expect to help researchers on which rodent models are adequate for research of specific behavioral manifestations of autism, which potentially require a combination of them depending on the research interest. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021226299 .
Assuntos
Transtorno do Espectro Autista , Animais , Transtorno do Espectro Autista/genética , Modelos Animais de Doenças , Proteína do X Frágil da Deficiência Intelectual , Humanos , Metanálise como Assunto , Camundongos , Proteínas dos Microfilamentos , Proteínas do Tecido Nervoso , Metanálise em Rede , Roedores , Revisões Sistemáticas como AssuntoRESUMO
Approximately one-third of individuals with major depressive disorder are resistant to conventional antidepressants (i.e., monoamine-based therapies), and, even among respondents, a proper therapeutic effect may require weeks of treatment. Ketamine, a racemic mixture of the two enantiomers, (R)-ketamine and (S)-ketamine, is an N-methyl-d-aspartate receptor (NMDAR) antagonist and has been shown to have rapid-acting antidepressant properties in patients with treatment-resistant depression (TRD). Although (R)-ketamine has a lower affinity for NMDAR, it presents greater potency and longer-lasting antidepressant properties, with no major side effects, than racemic ketamine or (S)-ketamine in preclinical findings. Thereby, ketamine and its enantiomers have not only an antagonistic effect on NMDAR but also a strong synaptogenic-modulatory effect, which is impaired in TRD pathophysiology. In this review, we summarize the current evidence regarding the modulation of neurotransmission, neuroplasticity, and neural network activity as putative mechanisms of these rapid-acting antidepressants, highlighting differences on intracellular signaling pathways of synaptic proteins such as mammalian target of rapamycin (mTOR), extracellular signal-regulated kinase (ERK) and brain-derived neurotrophic factor (BDNF). In addition, we discuss probable mechanisms involved in the side effects of ketamine and its enantiomers.
Assuntos
Transtorno Depressivo Maior , Ketamina , Antidepressivos/efeitos adversos , Depressão/metabolismo , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Ketamina/efeitos adversos , Receptores de N-Metil-D-Aspartato/metabolismoRESUMO
The impact of stress on health and well-being is determined by the ability of an individual to cope with challenges imposed by the stressor. Animals exposed to social defeat stress show different patterns of response during confrontations, leading to distinct stress-induced consequences. Using an established resident-intruder paradigm, we explored the outcomes of adopting active or passive coping strategies during a social defeat protocol over peripheral and central nervous system (CNS) levels of inflammatory cytokines, growth factors, glucocorticoid, and oxidative stress markers in male Wistar rats. Animals that presented short latency to assume a defeated posture during confrontation-considered as susceptible to stress-exhibited increased levels of brain-derived neurotrophic factor (BDNF) in the amygdala (AMY) and in the bed nucleus of the stria terminalis (BNST), and decreased lipid peroxidation in the CNS, suggesting changes in antioxidative defenses as well as stress-induced neuroadaptations. On the other hand, animals with longer latencies to assume a submissive posture-considered to be resilient to stress-presented lower levels of CNS BDNF compared to short-latency animals and decreased enzymatic antioxidant defenses in the CNS in comparison to controls, which might indicate an increased risk of central oxidative damage. From the results, behavioral reactivity cannot be considered a predictor of success in responding to stress; however, the findings of this study reinforce the idea that exposure to stress has no predetermined negative effects. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Assuntos
Derrota Social , Estresse Psicológico , Adaptação Psicológica , Animais , Masculino , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Ratos WistarRESUMO
Introduction In addition to their role in regulation of the hypothalamic-pituitary-adrenal-axis, corticotropin-releasing factor (CRF) and its related peptides, the urocortins, are important mediators of physiological and pathophysiological processes of the central nervous, cardiovascular, gastrointestinal, immune, endocrine, reproductive, and skin systems. Altered regulation of CRF-mediated adaptive responses to various stressful stimuli disrupts healthy function and might confer vulnerability to several disorders, including depression and anxiety. Methodology This narrative review was conducted through search and analysis of studies retrieved from online databases using a snowball method. Results This review covers aspects beginning with the discovery of CRF, CRF binding protein and their actions via interaction with CRF receptors type 1 and type 2. These are surface plasma membrane receptors, activation of which is associated with conformational changes and interaction with a variety of G-proteins and signaling pathways. We also reviewed the pharmacology and mechanisms of the receptor signaling modulatory activity of these receptors. Conclusion This review compiles and presents knowledge regarding the CRFergic system, including CRF related peptides, CRF binding protein, and CRF receptors, as well as some evidence that is potentially indicative of the biological roles of these entities in several physiological and pathophysiological processes.
Assuntos
Hormônio Liberador da Corticotropina/fisiologia , Sistema Hipotálamo-Hipofisário/metabolismo , Receptores de Hormônio Liberador da Corticotropina/fisiologia , Transdução de Sinais/fisiologia , Estresse Psicológico/metabolismo , Animais , Hormônio Liberador da Corticotropina/metabolismo , Humanos , Receptores de Hormônio Liberador da Corticotropina/metabolismoRESUMO
Abstract Introduction In addition to their role in regulation of the hypothalamic-pituitary-adrenal-axis, corticotropin-releasing factor (CRF) and its related peptides, the urocortins, are important mediators of physiological and pathophysiological processes of the central nervous, cardiovascular, gastrointestinal, immune, endocrine, reproductive, and skin systems. Altered regulation of CRF-mediated adaptive responses to various stressful stimuli disrupts healthy function and might confer vulnerability to several disorders, including depression and anxiety. Methodology This narrative review was conducted through search and analysis of studies retrieved from online databases using a snowball method. Results This review covers aspects beginning with the discovery of CRF, CRF binding protein and their actions via interaction with CRF receptors type 1 and type 2. These are surface plasma membrane receptors, activation of which is associated with conformational changes and interaction with a variety of G-proteins and signaling pathways. We also reviewed the pharmacology and mechanisms of the receptor signaling modulatory activity of these receptors. Conclusion This review compiles and presents knowledge regarding the CRFergic system, including CRF related peptides, CRF binding protein, and CRF receptors, as well as some evidence that is potentially indicative of the biological roles of these entities in several physiological and pathophysiological processes.
Assuntos
Animais , Humanos , Estresse Psicológico/metabolismo , Hormônio Liberador da Corticotropina/fisiologia , Transdução de Sinais/fisiologia , Receptores de Hormônio Liberador da Corticotropina/fisiologia , Sistema Hipotálamo-Hipofisário/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Receptores de Hormônio Liberador da Corticotropina/metabolismoRESUMO
Social stress is recognized to promote the development of neuropsychiatric and mood disorders. Corticotropin releasing factor (CRF) is an important neuropeptide activated by social stress, and it contributes to neural and behavioral adaptations, as indicated by impaired social interactions and anhedonic effects. Few studies have focused on the role of the CRF binding protein (CRFBP), a component of the CRF system, and its activity in the bed nucleus of stria terminalis (BNST), a limbic structure connecting amygdala and hypothalamus. In this study, animals' preference for sweet solutions was examined as an index of stress-induced anhedonic responses in Wistar rats subjected to four brief intermittent episodes of social defeat. Next, social approach was assessed after local infusions of the CRFBP antagonist, CRF fragment 6-33 (CRF6-33) into the BNST. The experience of brief episodes of social defeat impaired social approach behaviors in male rats. However, intra-BNST CRF6-33 infusions restored social approach in stressed animals to the levels of non-stressed rats. CRF6-33 acted selectively on social interaction and did not alter general exploration in nether stressed nor non-stressed rats. These findings suggest that BNST CRFBP is involved in the modulation of anxiety-like responses induced by social stress.
Assuntos
Hormônio Liberador da Corticotropina/uso terapêutico , Antagonistas de Hormônios/uso terapêutico , Núcleos Septais/efeitos dos fármacos , Transtornos do Comportamento Social/tratamento farmacológico , Transtornos do Comportamento Social/etiologia , Estresse Psicológico/complicações , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Masculino , Fragmentos de Peptídeos/uso terapêutico , Ratos , Ratos Wistar , Núcleos Septais/metabolismoRESUMO
Hyper activation of the neuroimmune system is strongly related to the development of neuropsychiatric disorders. Psychosocial stress has been postulated to play an important role in triggering anxiety and major depression. In preclinical models, there is mounting evidence that social defeat stress activates microglial cells in the central nervous system. This type of stress could be one of the major factors in the development of these psychopathologies. Here, we reviewed the most recent literature on social defeat and the associated immunological reactions. We focused our attention on microglial cells and kept the effect of social defeat over microglia separate from the effect of this stressor on other immune cells and the influence of peripheral immune components in priming central immune reactions. Furthermore, we considered how social defeat stress affects microglial cells and the consequent development of anxiety- and depressive-like states in preclinical studies. We highlighted evidence for the negative impact of the over-activation of the neuroimmune system, especially by the overproduction of pro-inflammatory mediators and cytotoxins. Overproduction of these molecules may cause cellular damage and loss or decreased function of neuronal activity by excessively pruning synaptic connections that ultimately contribute to the development of anxiety- and depressive-like states.
RESUMO
Despite advances in the characterization of developmental dyslexia (DD), several questions regarding the interplay between DD-susceptibility genes and environmental risk factors remain open. This systematic review aimed at answering the following questions: What has been the impact of new resources on the knowledge about DD? Which questions remain open? What is the investigative agenda for the short term? Forty-six studies were analyzed. Despite the growing literature on DD candidate genes, most studies have not been replicated. We found large effects on causative genes and smaller environmental contributions, involving maternal smoking during pregnancy, SES and the DYX1C1-1259C/G marker. Implications are discussed.
Assuntos
Dislexia/etiologia , Dislexia/genética , Exposição Ambiental/efeitos adversos , Criança , Feminino , Humanos , Masculino , Gravidez , Fatores de RiscoRESUMO
Gene expression related to the formation and modification of memories is regulated epigenetically by chromatin remodeling through histone acetylation. Memory formation and extinction can be enhanced by treatment with inhibitors of histone deacetylases (HDACs). The basolateral amygdala (BLA) is a brain area critically involved in regulating memory for inhibitory avoidance (IA). However, previous studies have not examined the effects of HDAC inhibition in the amygdala on memory for IA. Here we show that infusion of an HDAC inhibitor (HDACi), trichostatin A (TSA), into the BLA, enhanced consolidation of IA memory in rats when given at 1.5, 3, or 6 h posttraining, but not when the drug was infused immediately after training. In addition, intra-BLA administration of TSA immediately after retrieval delayed extinction learning. Moreover, we show that intra-BLA TSA in rats given IA training increased the levels of brain-derived neurotrophic factor in the dorsal hippocampus, but not in the BLA itself. These findings reveal novel aspects of the regulation of fear memory by epigenetic mechanisms in the amygdala.
RESUMO
INTRODUCTION:: Agonistic behaviors help to ensure survival, provide advantage in competition, and communicate social status. The resident-intruder paradigm, an animal model based on male intraspecific confrontations, can be an ethologically relevant tool to investigate the neurobiology of aggressive behavior. OBJECTIVES:: To examine behavioral and neurobiological mechanisms of aggressive behavior in male Swiss mice exposed to repeated confrontations in the resident intruder paradigm. METHODS:: Behavioral analysis was performed in association with measurements of plasma corticosterone of mice repeatedly exposed to a potential rival nearby, but inaccessible (social instigation), or to 10 sessions of social instigation followed by direct aggressive encounters. Moreover, corticotropin-releasing factor (CRF) and brain-derived neurotrophic factor (BNDF) were measured in the brain of these animals. Control mice were exposed to neither social instigation nor aggressive confrontations. RESULTS:: Mice exposed to aggressive confrontations exhibited a similar pattern of species-typical aggressive and non-aggressive behaviors on the first and the last session. Moreover, in contrast to social instigation only, repeated aggressive confrontations promoted an increase in plasma corticosterone. After 10 aggressive confrontation sessions, mice presented a non-significant trend toward reducing hippocampal levels of CRF, which inversely correlated with plasma corticosterone levels. Conversely, repeated sessions of social instigation or aggressive confrontation did not alter BDNF concentrations at the prefrontal cortex and hippocampus. CONCLUSION:: Exposure to repeated episodes of aggressive encounters did not promote habituation over time. Additionally, CRF seems to be involved in physiological responses to social stressors.
Assuntos
Agressão/fisiologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Corticosterona/sangue , Hormônio Liberador da Corticotropina/metabolismo , Sistema Límbico/metabolismo , Córtex Pré-Frontal/metabolismo , Análise de Variância , Animais , Comportamento Animal/fisiologia , Ensaio de Imunoadsorção Enzimática , Habituação Psicofisiológica/fisiologia , Abrigo para Animais , Masculino , CamundongosRESUMO
Abstract Introduction: Agonistic behaviors help to ensure survival, provide advantage in competition, and communicate social status. The resident-intruder paradigm, an animal model based on male intraspecific confrontations, can be an ethologically relevant tool to investigate the neurobiology of aggressive behavior. Objectives: To examine behavioral and neurobiological mechanisms of aggressive behavior in male Swiss mice exposed to repeated confrontations in the resident intruder paradigm. Methods: Behavioral analysis was performed in association with measurements of plasma corticosterone of mice repeatedly exposed to a potential rival nearby, but inaccessible (social instigation), or to 10 sessions of social instigation followed by direct aggressive encounters. Moreover, corticotropin-releasing factor (CRF) and brain-derived neurotrophic factor (BNDF) were measured in the brain of these animals. Control mice were exposed to neither social instigation nor aggressive confrontations. Results: Mice exposed to aggressive confrontations exhibited a similar pattern of species-typical aggressive and non-aggressive behaviors on the first and the last session. Moreover, in contrast to social instigation only, repeated aggressive confrontations promoted an increase in plasma corticosterone. After 10 aggressive confrontation sessions, mice presented a non-significant trend toward reducing hippocampal levels of CRF, which inversely correlated with plasma corticosterone levels. Conversely, repeated sessions of social instigation or aggressive confrontation did not alter BDNF concentrations at the prefrontal cortex and hippocampus. Conclusion: Exposure to repeated episodes of aggressive encounters did not promote habituation over time. Additionally, CRF seems to be involved in physiological responses to social stressors.
Resumo Introdução: Comportamentos agonísticos ajudam a garantir a sobrevivência, oferecem vantagem na competição e comunicam status social. O paradigma residente-intruso, modelo animal baseado em confrontos intraespecíficos entre machos, pode ser uma ferramenta etológica relevante para investigar a neurobiologia do comportamento agressivo. Objetivos: Analisar os mecanismos comportamentais e neurobiológicos do comportamento agressivo em camundongos Swiss machos expostos a confrontos repetidos no paradigma residente-intruso. Métodos: A análise comportamental foi realizada em associação com medidas de corticosterona plasmática em camundongos expostos repetidamente a um rival em potencial próximo, porém inacessível (instigação social), ou a 10 sessões de instigação social seguidas de encontros agressivos diretos. Além disso, o fator de liberação de corticotrofina (CRF) e o fator neurotrófico derivado do cérebro (BNDF) foram medidos no encéfalo desses animais. Camundongos controles não foram expostos à instigação social ou confrontos agressivos. Resultados: Os camundongos expostos a confrontos agressivos exibiram um padrão semelhante de comportamentos agressivos e não agressivos típicos da espécie na primeira e na última sessão. Em contraste com instigação social apenas, confrontos agressivos repetidos promoveram aumento na corticosterona plasmática. Após 10 sessões de confrontos agressivos, os camundongos apresentaram uma tendência não significativa de redução dos níveis de CRF no hipocampo, que se correlacionaram inversamente com os níveis plasmáticos de corticosterona. Por outro lado, sessões repetidas de instigação social ou confronto agressivo não alteraram as concentrações de BDNF no córtex pré-frontal e hipocampo. Conclusão: A exposição a episódios repetidos de encontros agressivos não promoveu habituação ao longo do tempo. Adicionalmente, o CRF parece estar envolvido nas respostas fisiológicas aos estressores sociais.
Assuntos
Animais , Masculino , Corticosterona/sangue , Hormônio Liberador da Corticotropina/metabolismo , Córtex Pré-Frontal/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Agressão/fisiologia , Sistema Límbico/metabolismo , Comportamento Animal/fisiologia , Ensaio de Imunoadsorção Enzimática , Análise de Variância , Habituação Psicofisiológica/fisiologia , Abrigo para Animais , CamundongosRESUMO
The tactical use of visuoperceptual content in marketing may encourage impulsive consumption of unhealthy products. In this study, the application of visuoperceptual content was compared in advertisements used by industries of tobacco, alcohol and food. The aim was to ascertain whether similarities exist in the strategies used as variables for the selection of commercial stimuli, such as color, position and size. Scion Image and Corel Draw Graphics Suite software were used to analyze the content of a non-probabilistic sample of advertising images (N = 150). Differences were identified in the use of the colors green (p = 0.04) and red (p = 0.01), but not in the use of the color blue (p = 0.64), suggesting that induction of feelings of pleasantness resulting from the use of the color blue may be associated with the advertising in the alcohol and tobacco industries. Regarding the position of the commercial stimuli, a predominance of the use of quadrants 'C' (p = 0.00) and 'D' (p = 0.01) was found in all three industries, indicating a similar use of areas perceived as being 'heavier'. As to the size, 78% of advertisements placed the commercial stimuli within a range of 0-25% of the total image. The results showed some similarities in the use of visuoperceptual content in advertisements for tobacco, alcohol and food, especially between tobacco and alcohol. The article offers a convergence analysis of these three industries altogether, providing additional subsidies for the formulation of protection policies.
Assuntos
Publicidade , Bebidas Alcoólicas , Fast Foods , Produtos do Tabaco , Publicidade/métodos , Brasil , Cor , Humanos , Marketing/métodos , Estimulação LuminosaRESUMO
INTRODUCTION: Social defeat (SD) in rats, which results from male intraspecific confrontations, is ethologically relevant and useful to understand stress effects on physiology and behavior. METHODS: A systematic review of studies about biomarkers induced by the SD protocol and published from 2002 to 2013 was carried out in the electronic databases PubMed, Web of Knowledge and ScienceDirect. The search terms were: social defeat, rat, neurotrophins, neuroinflammatory markers, and transcriptional factors. RESULTS: Classical and recently discovered biomarkers were found to be relevant in stress-induced states. Findings were summarized in accordance to the length of exposure to stress: single, repeated, intermittent and continuous SD. This review found that the brain-derived neurotrophic factor (BDNF) is a distinct marker of stress adaptation. Along with glucocorticoids and catecholamines, BDNF seems to be important in understanding stress physiology. CONCLUSION: The SD model provides a relevant tool to study stress response features, development of addictive behaviors, clinic depression and anxiety, as well as individual differences in vulnerability and resilience to stress.
Assuntos
Estresse Psicológico/metabolismo , Animais , Biomarcadores/metabolismo , Modelos Animais de Doenças , Dominação-Subordinação , Individualidade , Transtornos do Humor/metabolismo , Ratos , Resiliência Psicológica , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Revisões Sistemáticas como AssuntoRESUMO
Introduction: Social defeat (SD) in rats, which results from male intraspecific confrontations, is ethologically relevant and useful to understand stress effects on physiology and behavior. Methods: A systematic review of studies about biomarkers induced by the SD protocol and published from 2002 to 2013 was carried out in the electronic databases PubMed, Web of Knowledge and ScienceDirect. The search terms were: social defeat, rat, neurotrophins, neuroinflammatory markers, and transcriptional factors. Results: Classical and recently discovered biomarkers were found to be relevant in stress-induced states. Findings were summarized in accordance to the length of exposure to stress: single, repeated, intermittent and continuous SD. This review found that the brain-derived neurotrophic factor (BDNF) is a distinct marker of stress adaptation. Along with glucocorticoids and catecholamines, BDNF seems to be important in understanding stress physiology. Conclusion: The SD model provides a relevant tool to study stress response features, development of addictive behaviors, clinic depression and anxiety, as well as individual differences in vulnerability and resilience to stress. .
Introdução: A derrota social (social defeat, SD) entre ratos, resultado da confrontação intraespecífica entre machos, é etologicamente relevante e útil para o entendimento dos efeitos do estresse na fisiologia e no comportamento. Métodos: Foi realizada uma revisão sistemática de estudos sobre biomarcadores induzidos pelo protocolo de SD publicados entre 2002 e 2013, usando as bases de dados PubMed, Web of Knowledge e ScienceDirect. Os termos usados na busca foram: derrota social, neurotrofinas, marcadores neuroinflamatórios e fatores de transcrição. Resultados: Biomarcadores clássicos ou recentemente descobertos mostraram-se relevantes nos estados induzidos pelo estresse. Os achados foram resumidos de acordo com o tempo de exposição ao estresse: SD única, repetida, intermitente ou contínua. O fator neurotrófico derivado do cérebro se mostrou um marcador específico de adaptação ao estresse. Assim como glicocorticóides e catecolaminas, o BDNF parece ser importante para o entendimento da fisiologia do estresse. Conclusão: O modelo de SD oferece uma ferramenta importante para estudar características da resposta ao estresse, desenvolvimento de comportamentos aditivos, depressão clínica e ansiedade, bem como diferenças individuais de vulnerabilidade e resiliência ao estresse. .