RESUMO
Excitotoxicity is described as the exacerbated activation of glutamate AMPA and NMDA receptors that leads to neuronal damage, and ultimately to cell death. Astrocytes are responsible for the clearance of 80-90% of synaptically released glutamate, preventing excitotoxicity. Chronic stress renders neurons vulnerable to excitotoxicity and has been associated to neuropsychiatric disorders, i.e., anxiety. Microreactors containing platinum nanoparticles (Pt-NP) and glutamate dehydrogenase have shown in vitro activity against excitotoxicity. The purpose of the present study was to investigate the in vivo effects of these microreactors on the behavioral and neurobiological effects of chronic stress exposure. Rats were either unstressed or exposed for 2 weeks to an unpredictable chronic mild stress paradigm (UCMS), administered intra-ventral hippocampus with the microreactors (with or without the blockage of astrocyte functioning), and seven days later tested in the elevated T-maze (ETM; Experiment 1). The ETM allows the measurement of two defensive responses, avoidance and escape, in terms of psychopathology respectively related to generalized anxiety and panic disorder. Locomotor activity in an open field was also measured. Since previous evidence shows that stress inhibits adult neurogenesis, we evaluated the effects of the different treatments on the number of cells expressing the marker of migrating neuroblasts doublecortin (DCX) in the dorsal and ventral hippocampus (Experiment 2). Results showed that UCMS induces anxiogenic effects, increases locomotion, and decreases the number of DCX cells in the dorsal and ventral hippocampus, effects that were counteracted by microreactor administration. This is the first study to demonstrate the in vivo efficacy of Pt-NP against the behavioral and neurobiological effects of chronic stress exposure.
Assuntos
Nanopartículas Metálicas , Platina , Animais , Ratos , Platina/metabolismo , Ratos Wistar , Neurogênese/fisiologia , Hipocampo/metabolismo , Ansiedade/tratamento farmacológico , Ansiedade/patologia , Ácido Glutâmico/metabolismoRESUMO
BACKGROUND: The COVID-19 pandemic raises concerns about the mental health of the world population. Protection measures to prevention the disease impacted education and undergraduate students were exposed to additional stressors. OBJECTIVES: Analyze depression, anxiety and stress symptoms in undergraduates, their respective predictors and the association with satisfaction with life, psychological well-being and coping strategies. METHODS: An online cross-sectional study was conducted from September 14 to October 19, 2020, involving undergraduate students enrolled in 33 courses from 5 public university campuses in the state of Parana, Brazil, using: questionnaire with sociodemographic, academic, health and pandemic effects variables; Depression, Anxiety and Stress Scale-21 (DASS-21); Satisfaction with Life Scale (SWLS); Psychological Well-Being (PWB); BriefCOPE. The convenience sample was composed of 1,224 participants, with 18 years old or older, that completed all research instruments. Spearman correlation and logistic analysis (univariate and multivariate) were applied to the collected data. RESULTS: Most of the undergraduates presented symptoms of depression (60.5%), anxiety (52.5%) and stress (57.5%). Depression, anxiety and stress presented significant correlations in common: negative with satisfaction with life, all dimensions of psychological well-being, and 3 adaptive copings (active coping, planning, positive reframing); positive with 5 maladaptive copings (behavioral disengagement, denial, self-blame, self-distraction, substance use). In addition, there were 7 common predictors for symptoms of depression, anxiety and stress: female; age 18-24 years old; having a chronic disease; lower scores in 2 dimensions of psychological well-being (positive relations with others, self-acceptance); higher scores in 2 maladaptive copings (self-blame, substance use). CONCLUSIONS: The data indicate a high prevalence of symptoms of depression, anxiety and stress, and suggest that higher scores of satisfaction with life, psychological well-being dimensions and adaptive copings may present protective effects in undergraduates during a pandemic crisis.
Assuntos
Adaptação Psicológica , Ansiedade/patologia , COVID-19/epidemiologia , Depressão/patologia , Estresse Psicológico , Estudantes/psicologia , Adolescente , Adulto , Brasil/epidemiologia , COVID-19/virologia , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Satisfação Pessoal , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Inquéritos e Questionários , Universidades , Adulto JovemRESUMO
Health professionals may be a vulnerable group to posttraumatic stress symptoms (PTSS) during the Coronavirus disease 2019 (COVID-19) pandemic. To investigate how health professionals who experienced a traumatic event are expressing PTSS and factors related to risk for higher PTSS symptomatology can inform how health professionals are facing their role in this crisis. This was an Internet cross-sectional survey. Participants were 49,767 Brazilian health professionals who have ever faced a traumatic event, which was about 25.9% of an initial sample of health professionals. PTSS symptoms were assessed using the Impact of Event Scale-Revised (IES-R) and latent profile analysis (LPA) explored subpopulations within participants based on their scores. Distinct profiles were compared for psychological distress (e.g., depression and anxiety) and quality of life. Multinomial logistic regression analysis was conducted to investigate the relationship between IES-R profiles and COVID-19 related experiences, thoughts, and perceptions. A two-profile model was the most appropriate for the IES-R data pointing out a group with a high level of PTSS (named high-PTSS; n = 10,401, 20.9%) and another expressing a low level of symptoms (named low-PTSS; n = 39,366, 79.1%). The high-PTSS profile demonstrated worse psychological scores (global psychological distress, somatization, depression, and anxiety) and worse quality of life (physical, psychological, social, and environmental) with moderate magnitudes. Small but significant predictors of the high-PTSS profile included sociodemographic characteristics and COVID-19 related experiences, thoughts, and perceptions. Most individuals who experienced a traumatic event were not in the high-PTSS profile. For those who were, however, psychological and quality of life measures were much worse. During the initial phase of the COVID-19 pandemic, several characteristics emerged as risks to report trauma.
Assuntos
COVID-19/epidemiologia , Pessoal de Saúde/psicologia , Transtornos de Estresse Pós-Traumáticos/patologia , Adulto , Ansiedade/patologia , Brasil/epidemiologia , COVID-19/virologia , Estudos Transversais , Depressão/patologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pandemias , Angústia Psicológica , Qualidade de Vida , Fatores de Risco , SARS-CoV-2/isolamento & purificaçãoRESUMO
Tuberculosis (TB) is an important infectious disease and a public health problem. The organs most frequently affected by TB are the lungs; despite this, it has been reported that TB patients suffer from depression and anxiety, which have been attributed to social factors. In previous experimental work, we observed that the extensive pulmonary inflammation characteristic of TB with high cytokine production induces neuroinflammation, neuronal death and behavioral abnormalities in the absence of brain infection. The objective of the present work was to reduce this neuroinflammation and avoid the psycho-affective disorders showed during pulmonary TB. Glucocorticoids (GCs) are the first-line treatment for neuroinflammation; however, their systemic administration generates various side effects, mostly aggravating pulmonary TB due to immunosuppression of cellular immunity. Intranasal administration is a route that allows drugs to be released directly in the brain through the olfactory nerve, reducing their doses and side effects. In the present work, dexamethasone's (DEX) intranasal administration was evaluated in TB BALB /c mice comparing three different doses (0.05, 0.25 and 2.5 mg/kg BW) on lung disease evolution, neuroinflammation and behavioral alterations. Low doses of dexamethasone significantly decreased neuroinflammation, improving behavioral status without aggravating lung disease.
Assuntos
Encéfalo/efeitos dos fármacos , Dexametasona/farmacologia , Inflamação/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Administração Intranasal , Animais , Ansiedade/complicações , Ansiedade/tratamento farmacológico , Ansiedade/patologia , Encéfalo/patologia , Depressão/complicações , Depressão/tratamento farmacológico , Depressão/patologia , Modelos Animais de Doenças , Glucocorticoides/farmacologia , Humanos , Inflamação/complicações , Inflamação/microbiologia , Inflamação/patologia , Camundongos , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/patogenicidade , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologiaRESUMO
INTRODUCTION: SARS-Cov-2 virus pandemic causes serious emotional consequences. It has occurred widespread medical courses suspension, and graduations were anticipated. Field hospitals, set up to treat patients with mild to moderate COVID-19, were the main workplaces of newly graduated doctors. OBJECTIVE: To assess the impact of SARS-Cov-2/COVID-19 pandemic on mental health of medical interns and newly graduated doctors. METHOD: This is a cross-sectional study performed using a digital platform. Links to forms were sent in two moments: moment 1 (M1), at the beginning of the pandemic, in the first half of April/2020 and moment 2 (M2), after six months of pandemic, in the second half of September/2020. All students from the medical internship and all doctors graduated since 2018 from the three medical schools in Sergipe-NE-Brazil were invited. RESULTS: 335 forms were answered in April and 148 in September. In M1 88.9% considered themselves exposed to excess of information about COVID-19, which was associated with anxiety symptoms (p = 0.04). Long family physical distance was also associated with these symptoms, as increased appetite (p = 0.01), feeling shortness of breath (p = 0.003) and sweating (p = 0.007). Fear of acquire COVID-19 was reported as intense by almost half of participants, and of transmitting by 85.7% in M1. In M2 41.2% reported the death of friends or relatives. Psychiatric illness was described by 38.5% and psychotropic drugs use by 30.1% in M1, especially those who lived alone (p = 0.03) and the single ones (p = 0.01). Alcohol intake was reported by 54.3%, and among doctors graduated in 2020 it increased from 50% in M1 to 85% in M2 (p = 0.04). CONCLUSION: The pandemic had a negative impact on the mental health of medical students and newly graduated doctors. Exposure to excessive COVID-19 information and family physical distance were associated to anxiety symptoms. Among doctors graduated in 2020, alcohol intake increased during pandemic evolution.
Assuntos
Ansiedade/patologia , COVID-19/epidemiologia , Saúde Mental , Médicos/psicologia , Estudantes de Medicina/psicologia , Adulto , Consumo de Bebidas Alcoólicas , Ansiedade/tratamento farmacológico , Brasil/epidemiologia , COVID-19/patologia , COVID-19/virologia , Estudos Transversais , Feminino , Humanos , Internato e Residência , Masculino , Pandemias , Psicotrópicos/uso terapêutico , SARS-CoV-2/isolamento & purificação , Adulto JovemRESUMO
The COVID-19 pandemic has become one of the main international concerns regarding its impact on mental health. The present study aims to investigate the prevalence of depression, anxiety, and stress symptoms, and behavioral aspects amidst the COVID-19 pandemic in a Brazilian population. An online survey was administered from May 22 to June 5, 2020 using a questionnaire comprising of sociodemographic information, the Depression, Anxiety, and Stress Scale (DASS-21), and the Coping Strategies Inventory. Participants comprised 3,000 people from Brazil's 26 states and the Federal District, with an average age of 39.8 years, women (83%), married (50.6%), graduates (70.1%) and employees (46.7%). Some contracted the virus (6.4%) and had dead friends or relatives (22.7%). There was more consumption of drugs, tobacco, medication, and food (40.8%). Almost half of participants expressed symptoms of depression (46.4%), anxiety (39.7%), and stress (42.2%). These were higher in women, people without children, students, patients with chronic diseases, and people who had contact with others diagnosed with COVID-19. The existence of a group more vulnerable to situations with a high stress burden requires greater attention regarding mental health during and after the pandemic. That said, it should be emphasized that these findings are preliminary and portray a moment still being faced by many people amid the pandemic and quarantine measures. Therefore, we understand that the magnitude of the impacts on mental health will only be more specific with continuous studies after total relaxation of the quarantine.
Assuntos
Ansiedade/patologia , COVID-19/patologia , Depressão/patologia , Estresse Psicológico , Adaptação Psicológica , Adolescente , Adulto , Idoso , Ansiedade/epidemiologia , Brasil/epidemiologia , COVID-19/virologia , Depressão/epidemiologia , Feminino , Humanos , Internet , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/isolamento & purificação , Inquéritos e Questionários , Adulto JovemRESUMO
Mice cohabiting with a conspecific in chronic pain display anxiogenesis in the elevated plus-maze (EPM). Given that the anterior cingulate (ACC) and insular (InC) cortices play a role in the modulation of anxiety, pain, and emotional contagion, we investigated (a) the FosB activation in both brain areas and (b) the effects of intra-ACC or -InC injection of cobalt chloride (CoCl2, a synaptic blocker), on the anxiety of mice cohabiting with a cagemate suffering pain. Twenty-one days after birth, male Swiss mice were housed in pairs for 14 days to establish familiarity. On the 14th day, mice were divided into two groups: cagemate sciatic nerve constriction (CNC; i.e., one animal of each pair was subjected to sciatic nerve constriction), and cagemate sham (CS; i.e., a similar procedure but without suffering nerve constriction). After that, both groups were housed again with the same pairs for the other 14 days. On the 28th day, mice had their brains removed for the immunoassays analyses (Exp. 1). For experiments 2 and 3, on the 23rd day, the cagemates received guide cannula implantation bilaterally in the ACC or InC and, on the 28th day, they received local injections of saline or CoCl2, and then were exposed to the EPM. Results showed that cohabitation with a conspecific with chronic pain decreases and increases neuronal activation (FosB) within the ACC and InC, respectively. Intra-ACC or InC injection of CoCl2 reversed the anxiogenic effect in those animals that cohabited with a conspecific in chronic pain. ACC and InC seem to modulate anxiety induced by emotional contagion in animals cohabitating with a conspecific suffering pain.
Assuntos
Ansiedade/metabolismo , Dor Crônica/metabolismo , Empatia/fisiologia , Giro do Cíngulo/metabolismo , Córtex Insular/metabolismo , Interação Social , Animais , Ansiedade/patologia , Ansiedade/psicologia , Dor Crônica/patologia , Dor Crônica/psicologia , Giro do Cíngulo/patologia , Córtex Insular/patologia , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Neuropatia Ciática/patologia , Neuropatia Ciática/psicologiaRESUMO
The mechanisms underlying the neuroprotective effects of hesperidin in a murine model of PD are not fully elucidated. The current study was carried out to investigate the ability of hesperidin in modulating proinflammatory cytokines, neurotrophic factors, and neuronal recovery in 6-hydroxydopamine (6-OHDA)-induced nigral dopaminergic neuronal loss. Adult male C57BL/6 mice were randomly assigned into four groups: (I) sham/vehicle, (II) sham/hesperidin, (III) 6-OHDA/vehicle, and (IV) 6-OHDA/hesperidin. Mice received a unilateral intrastriatal injection of 6-OHDA and treated with hesperidin (50 mg/kg; per oral) for 28 days. After hesperidin treatment, mice were submitted to behavioral tests and had the striatum removed for neurochemical assays. Our results demonstrated that oral treatment with hesperidin ameliorated the anxiety-related and depressive-like behaviors in 6-OHDA-lesioned mice (p < 0.05). It also attenuated the striatal levels of proinflammatory cytokines tumor necrosis factor-α, interferon-gamma, interleukin-1ß, interleukin-2, and interleukin-6 and increased the levels of neurotrophic factors, including neurotrophin-3, brain-derived neurotrophic factor, and nerve growth factor in the striatum of 6-OHDA mice (p < 0.05). Hesperidin treatment was also capable to increase striatal levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid and protects against the impairment of dopaminergic neurons in the substantia nigra pars compacta (SNpc) (p < 0.05). In conclusion, this study indicated that hesperidin exerts anxiolytic-like and antidepressant-like effect against 6-OHDA-induced neurotoxicity through the modulation of cytokine production, neurotrophic factors levels, and dopaminergic innervation in the striatum.
Assuntos
Comportamento Animal/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Citocinas/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Hesperidina/farmacologia , Fatores de Crescimento Neural/metabolismo , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson Secundária/metabolismo , Animais , Ansiedade/metabolismo , Ansiedade/patologia , Corpo Estriado/metabolismo , Depressão/metabolismo , Depressão/patologia , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Masculino , Camundongos , Oxidopamina , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/patologiaRESUMO
In the last decade, increased homocysteine levels have been implicated as a risk factor for neurodegenerative and psychiatric disorders. We have developed an experimental model of chronic mild hyperhomocysteinemia (HHcy) in order to observe metabolic impairments in the brain of adult rodents. Besides its known effects on brain metabolism, the present study sought to investigate whether chronic mild HHcy could induce learning/memory impairments associated with biochemical and histological damage to the hippocampus. Adult male Wistar rats received daily subcutaneous injections of homocysteine (0.03 µmol/g of body weight) twice a day, from the 30th to the 60th day of life or saline solution (Controls). After injections, anxiety-like and memory tests were performed. Following behavioral analyses, brains were sliced and hippocampal volumes assessed and homogenized for redox state assessment, antioxidant activity, mitochondrial functioning (chain respiratory enzymes and ATP levels) and DNA damage analyses. Behavioral analyses showed that chronic mild HHcy may induce anxiety-like behavior and impair long-term aversive memory (24 h) that was evaluated by inhibitory avoidance task. Mild HHcy decreased locomotor and/or exploratory activities in elevated plus maze test and caused hippocampal atrophy. Decrease in cytochrome c oxidase, DNA damage and redox state changes were also observed in hippocampus of adult rats subjected to mild HHcy. Our findings show that chronic mild HHcy alters biochemical and histological parameters in the hippocampus, leading to behavioral impairments. These findings might be considered in future studies aiming to search for alternative strategies for treating the behavioral impairments in patients with mild elevations in homocysteine levels.
Assuntos
Ansiedade/etiologia , Hipocampo/patologia , Hiper-Homocisteinemia/complicações , Transtornos da Memória/etiologia , Trifosfato de Adenosina/metabolismo , Animais , Ansiedade/patologia , Atrofia/etiologia , Atrofia/patologia , Aprendizagem da Esquiva , Doença Crônica , Dano ao DNA/fisiologia , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Hipocampo/fisiopatologia , Homocisteína/sangue , Hiper-Homocisteinemia/induzido quimicamente , Masculino , Transtornos da Memória/fisiopatologia , Teste de Campo Aberto , Estresse Oxidativo/fisiologia , Ratos , Ratos WistarRESUMO
Sporadic Alzheimer's disease (sAD) is the most prevalent neurodegenerative pathology with no effective therapy until date. This disease promotes hippocampal degeneration, which in turn affects multiple cognitive domains and daily life activities. In this study, we hypothesized that long-lasting therapy with mesenchymal stem cells (MSC) would have a restorative effect on the behavioral alterations and cognitive decline typical of sAD, as they have shown neurogenic and immunomodulatory activities. To test this, we chronically injected intravenous human MSC in a sAD rat model induced by the intracerebroventricular injection of streptozotocin (STZ). During the last 2 weeks, we performed open field, Barnes maze, and marble burying tests. STZ-treated rats displayed a poor performance in all behavioral tests. Cell therapy increased exploratory behavior, decreased anxiety, and improved spatial memory and marble burying behavior, the latter being representative of daily life activities. On the hippocampus, we found that STZ promotes neuronal loss in the Cornus Ammoni (CA1) field and decreased neurogenesis in the dentate gyrus. Also, STZ induced a reduction in hippocampal volume and presynaptic protein levels and an exacerbated microgliosis, relevant AD features. The therapy rescued CA1 neurodegeneration but did not reverse the decrease of immature neurons, suggesting that the therapy effect varied among hippocampal neuronal populations. Importantly, cell therapy ameliorated microgliosis and restored hippocampal atrophy and some presynaptic protein levels in the sAD model. These findings, by showing that intravenous injection of human MSC restores behavioral and hippocampal alterations in experimental sAD, support the potential use of MSC therapy for the treatment of neurodegenerative diseases.