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INTRODUCTION: Inflammasome complexes, especially NLRP3, have gained great attention as a potential therapeutic target in mood disorders. NLRP3 triggers a caspase 1-dependent release of the inflammatory cytokines IL-1ß and IL-18, and seems to interact with purinergic and kynurenine pathways, all of which are implicated in mood disorders development and progression. AREAS COVERED: Emerging evidence supports NLRP3 inflammasome as a promising pharmacological target for mood disorders. We discussed the available evidence from animal models and human studies and provided a reflection on drawbacks and perspectives for this novel target. EXPERT OPINION: Several studies have supported the involvement of NLRP3 inflammasome in MDD. However, most of the evidence comes from animal models. The role of NLRP3 inflammasome in BD as well as its anti-manic properties is not very clear and requires further exploration. There is evidence of anti-manic effects of P2×R7 antagonists associated with reduction in the brain levels of IL-1ß and TNF-α in a murine model of mania. The involvement of other NLRP3 inflammasome expressing cells besides microglia, like astrocytes, and of other inflammasome complexes in mood disorders also deserves further investigation. Preclinical and clinical characterization of NLRP3 and other inflammasomes in mood disorders is needed before considering translational approaches, including clinical trials.
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Modelos Animais de Doenças , Inflamassomos , Terapia de Alvo Molecular , Transtornos do Humor , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/fisiopatologia , Camundongos , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/fisiopatologia , Antagonistas do Receptor Purinérgico P2X/farmacologia , Antagonistas do Receptor Purinérgico P2X/administração & dosagem , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/fisiopatologiaRESUMO
Introduction: Four years after the onset of the COVID-19 pandemic, the frequency of long-term post-COVID-19 cognitive symptoms is a matter of concern given the impact it may have on the work and quality of life of affected people. Objective: To evaluate the incidence of post-acute COVID-19 cognitive symptoms, as well as the associated risk factors. Methods: Retrospective cohort, including outpatients with laboratory-confirmed COVID-19 and who were assisted by a public telehealth service provided by the Telehealth Network of Minas Gerais (TNMG), during the acute phase of the disease, between December/2020 and March/2022. Data were collected through a structured questionnaire, applied via phone calls, regarding the persistence of COVID-19 symptoms after 12 weeks of the disease. Cognitive symptoms were defined as any of the following: memory loss, problems concentrating, word finding difficulties, and difficulty thinking clearly. Results: From 630 patients who responded to the questionnaire, 23.7% presented cognitive symptoms at 12 weeks after infection. These patients had a higher median age (33 [IQR 25-46] vs. 30 [IQR 24-42] years-old, p = 0.042) with a higher prevalence in the female sex (80.5% vs. 62.2%, p < 0.001) when compared to those who did not present cognitive symptoms, as well as a lower prevalence of smoking (8.7% vs. 16.2%, p = 0.024). Furthermore, patients with persistent cognitive symptoms were more likely to have been infected during the second wave of COVID-19 rather than the third (31.0% vs. 21.3%, p = 0.014). Patients who needed to seek in-person care during the acute phase of the disease were more likely to report post-acute cognitive symptoms (21.5% vs. 9.3%, p < 0,001). In multivariate logistic regression analysis, cognitive symptoms were associated with female sex (OR 2.24, CI 95% 1.41-3.57), fatigue (OR 2.33, CI 95% 1.19-4.56), depression (OR 5.37, CI 95% 2.19-13.15) and the need for seek in-person care during acute COVID-19 (OR 2.23, CI 95% 1.30-3.81). Conclusion: In this retrospective cohort of patients with mostly mild COVID-19, cognitive symptoms were present in 23.7% of patients with COVID-19 at 12 weeks after infection. Female sex, fatigue, depression and the need to seek in-person care during acute COVID-19 were the risk factors independently associated with this condition.
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COVID-19 , Telemedicina , Humanos , COVID-19/epidemiologia , Feminino , Estudos Retrospectivos , Masculino , Adulto , Pessoa de Meia-Idade , Telemedicina/estatística & dados numéricos , Fatores de Risco , Inquéritos e Questionários , SARS-CoV-2 , Brasil/epidemiologia , Disfunção Cognitiva/epidemiologia , Incidência , Adulto Jovem , Síndrome de COVID-19 Pós-Aguda , Qualidade de VidaRESUMO
Recent evidence has supported a pathogenic role for neuroinflammation in Parkinson's disease (PD). Inflammatory response has been associated with symptoms and subtypes of PD. However, it is unclear whether immune changes are involved in the initial pathogenesis of PD, leading to the non-motor symptoms (NMS) observed in its prodromal stage. The current study aimed to characterize the behavioral and cognitive changes in a toxin-induced model of prodromal PD-like syndrome. We also sought to investigate the role of neuroinflammation in prodromal PD-related NMS. Male mice were subjected to bilateral intranasal infusion with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or saline (control group), followed by comprehensive behavioral, pathological and neurochemical analysis. Intranasal MPTP infusion was able to cause the loss of dopaminergic neurons in the substantia nigra (SN). In parallel, it induced impairment in olfactory discrimination and social memory consolidation, compulsive and anxiety-like behaviors, but did not influence motor performance. Iba-1 and GFAP expressions were increased in the SN, suggesting an activated state of microglia and astrocytes. Consistent with this, MPTP mice had increased levels of IL-10 and IL-17A, and decreased levels of BDNF and TrkA mRNA in the SN. The striatum showed increased IL-17A, BDNF, and NFG levels compared to control mice. In conclusion, neuroinflammation may play an important role in the early stage of experimental PD-like syndrome, leading to cognitive and behavioral changes. Our results also indicate that intranasal administration of MPTP may represent a valuable mouse model for prodromal PD.
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Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Sintomas Prodrômicos , Substância Negra , Animais , Masculino , Substância Negra/metabolismo , Substância Negra/patologia , Substância Negra/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Doenças Neuroinflamatórias/patologia , Corpo Estriado/metabolismo , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/patologia , Camundongos , Microglia/metabolismo , Microglia/patologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ansiedade/etiologia , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologiaRESUMO
BACKGROUND: Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin that plays a crucial role in neuronal survival and plasticity. Previous studies have suggested that smoking may influence BDNF levels, but the findings have been inconsistent. METHODS: A comprehensive search of electronic databases was conducted to identify relevant studies. Inclusion criteria were applied to select studies that investigated the relationship between smoking and blood levels of BDNF. A random-effects model was used to estimate the overall effect size. RESULTS: A total of 23 studies were included. The meta-analysis revealed a significant association between smoking and increased blood levels of BDNF (standardized mean difference [SMD] = -0.38, 95 % confidence interval [CI] 0.15 to 0.62, p = 0.002). Subgroup analyses based on BDNF source showed a significant increase in plasma-derived BDNF levels (SMD = 1.02, 95 % CI 0.50 to 1.53, p = 0.0001), while no significant difference was observed in serum-derived BDNF levels (SMD = 0.02, 95 % CI -0.19 to 0.22, p = 0.87). The pooled analysis revealed a non-significant difference in blood levels of BDNF between former smokers and non-smokers (random-effects model, SMD = 0.21, 95 % CI -0.04 to 0.46, p = 0.1). CONCLUSION: Smokers exhibited significantly higher plasma levels of BDNF compared to non-smokers. Further research is needed to elucidate the underlying mechanisms and explore the potential therapeutic implications of targeting BDNF in smoking.
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Fator Neurotrófico Derivado do Encéfalo , Fumar , Humanos , Fumar TabacoRESUMO
INTRODUCTION: Strokes are traditionally attributed to risk factors like aging, hypertension, diabetes, and atherosclerosis. Chagas disease has emerged as an important risk factor for stroke in Latin American. Our study aims at describing the largest cohort of patients with Chagas disease and ischemic stroke and determining variables associated with stroke recurrence and cardioembolic cause. METHODS: This study is the result of a national multicenter cohort study conducted in Brazil. The study spanned from January 2009 to December 2016 and involved a comprehensive retrospective analysis of medical records of patients with both Chagas disease and stroke. This cohort comprised 499 individuals from diverse Brazilian regions, focusing on vascular risk factors and the epidemiological variables associated with Chagas disease and stroke. RESULTS: Our findings underscore the significant prevalence of traditional vascular risk factors among Chagas disease patients who had stroke. 81% of patients had hypertension, 56% dyslipidemia and 25% diabetes. We observed a 29.7% recurrence rate, especially within the cardioembolic subgroup. 56% of the patients had embolic stroke of undetermined source (ESUS). Specific EKG abnormalities were associated with an increased risk of cardioembolic etiology (with three altered results increasing 81fold the chance of the stroke being of cardioembolic nature). Age emerged as a protective factor (OR:0.98, CI 0.970 - 0.997) against cardioembolic etiology. Anticoagulation therapy was associated with reduced risk (OR:0.221 |CI 0.104 - 0.472), highlighting the importance of accurate etiological classification. Conversely, female gender(OR:1.83 CI 1.039 - 3.249) emerged as a significant risk factor for stroke recurrence. CONCLUSION: This study significantly advances our epidemiological understanding of the intersection between Chagas disease and stroke. It emphasizes the critical need for extensive epidemiological investigations, a deeper comprehension of stroke recurrence determinants, and accurate etiological classification to reduce the ESUS population. Our findings have substantial clinical implications, suggesting the need of control of vascular risk factors and comorbidities and hold promise for improving patient care and reducing the burden of Chagas disease and stroke worldwide.
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The factor RasGEF1b is a Ras guanine exchange factor involved in immune responses. Studies have also implicated RasGEF1b in the CNS development. It is still limited the understanding of the role of RasGEF1b in CNS functioning. Using RasGEF1b deficient mice (RasGEF1b-cKO), we investigated the impact of this gene deletion in behavior, cognition, brain neurochemistry and microglia morphology. We showed that RasGEF1b-cKO mice display spontaneous hyperlocomotion and anhedonia. RasGEF1b-cKO mice also exhibited compulsive-like behavior that was restored after acute treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (5 mg/kg). A down-regulation of mRNA of dopamine receptor (Drd1, Drd2, Drd4 and Drd5) and serotonin receptor genes (5Htr1a, 5Htr1b and 5Htr1d) was observed in hippocampus of RasGEF1b-cKO mice. These mice also had reduction of Drd1 and Drd2 in prefrontal cortex and 5Htr1d in striatum. In addition, morphological alterations were observed in RasGEF1b deficient microglia along with decreased levels of hippocampal BDNF. We provided original evidence that the deletion of RasGEF1b leads to unique behavioral features, implicating this factor in CNS functioning.
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Encéfalo , Inibidores Seletivos de Recaptação de Serotonina , Animais , Camundongos , Cognição , Fluoxetina/farmacologia , Córtex Pré-Frontal , Receptores de Dopamina D5RESUMO
OBJECTIVE: The impact of anxiety and depression on chemotherapy-induced oral mucositis has not been extensively explored in the literature. The aim of the present study was to evaluate anxiety/depressive symptoms, health-related quality of life, and oral health-related quality of life and their association with oral mucositis among individuals receiving chemotherapy. METHODS: This is a prospective longitudinal study carried out at a Brazilian referral service. The Hospital Anxiety and Depression Scale (HADS), World Health Organization Quality of Life-BREF (WHOQOL-BREF), and Oral Health Impact Profile questionnaire (OHIP-14) were applied at D0 (before chemotherapy) and D15 of chemotherapy. Clinicodemographic data and oral mucositis severity scores were evaluated. RESULTS: A total of 37 individuals (median age: 49 years) were included in the study. Nearly 38% of patients developed chemotherapy-induced oral mucositis and had higher anxiety/depression scores at baseline. Oral mucositis had a negative impact on oral health-related quality of life regarding functional limitation, physical pain, physical disability, and handicap. CONCLUSION: Anxiety/depressive symptoms are associated with oral mucositis that affects overall health and oral health-related quality of life.
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Antineoplásicos , Estomatite , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Depressão , Estudos Prospectivos , Estudos Longitudinais , Estomatite/induzido quimicamente , Estomatite/complicações , Ansiedade , Inquéritos e QuestionáriosRESUMO
RESUMO Objetivo Analisar a associação da independência funcional com aspectos clínicos de comprometimento neurológico, a localização e extensão do dano neuronal e os fatores sociodemográficos em pacientes na fase aguda do AVC. Método Estudo analítico de recorte transversal, realizado com 90 pacientes adultos e idosos acometidos por AVC isquêmico, que tiveram admissão no ambiente hospitalar nas primeiras 24 horas após o evento vascular. A coleta dos dados referentes aos aspectos clínicos e fatores sociodemográficos foi realizada pelo prontuário eletrônico e/ou entrevista para descrever o perfil dos pacientes, Oxfordshire Community Stroke Project, Alberta Stroke Programme Early CT Score, National Institute of Health Stroke Scale e a Medida de Independência Funcional. Resultados O comprometimento neurológico, de acordo com a National Institute of Health Stroke Scale, foi associado à funcionalidade nas primeiras 24 horas após o AVC. Além disso, a presença de hipertensão arterial, idade, trabalho inativo, tabagismo e extensão do dano neuronal estiveram associados à dependência funcional, mas não permaneceram no modelo final deste estudo. Conclusão A dependência funcional está associada à hipertensão arterial, idade, trabalho inativo, tabagismo, extensão do dano neuronal e grau de comprometimento neurológico nas primeiras 24 horas após o evento vascular. Além disso, um nível mais elevado de comprometimento neurológico foi independentemente associado a níveis aumentados de dependência funcional.
ABSTRACT Purpose To analyze the association of functional independence with clinical aspects of neurological impairment, the location and extent of neuronal damage and sociodemographic factors in patients in the acute phase of stroke. Methods Analytical cross-sectional study in 90 adult and older patients affected by ischemic stroke, admitted to the hospital within 24 hours of the vascular event. Sociodemographic factors and clinical aspects data were collected from electronic medical records and/or interviews in order to depict the patients'profile, Oxfordshire Community Stroke Project, Alberta Stroke Programme Early CT Score, National Institute of Health Stroke Scale, and Functional Independence Measure. Results Neurological impairment, according to the National Institute of Health Stroke Scale, was associated with functioning in the first 24 hours after the stroke. Furthermore, the presence of arterial hypertension, age, inactive work, smoking and extent of neuronal damage were associated with functional dependence, but did not remain in the final model of this study. Conclusion Functional dependence is associated with arterial hypertension, age, inactive work, smoking, extent of neuronal damage, and degree of neurological impairment in the first 24 hours after the vascular event. Furthermore, a higher level of neurological impairment was independently associated with increased levels of functional dependence.
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Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Atividades Cotidianas , Reação de Fase Aguda , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Estado Funcional , Fatores Sociodemográficos , PacientesRESUMO
Introduction: Migraine is a common and disabling primary headache, and its pathophysiology is not fully understood. Previous studies have suggested that pain can increase humans' Resting Energy Expenditure (REE). However, no previous study has investigated whether the REE of individuals with migraine differs from the general population. Therefore, this study aims to assess whether the REE of women with migraine differs from that of women without headaches. We also tested the accuracy of REE predictive formulas in the migraine patients. Methods: This cross-sectional study involves 131 adult women aged between 18 and 65 years, 83 with migraine and 48 without (controls). We collected clinical, demographic, and anthropometric data. Migraine severity was measured using the Migraine Disability Test and Headache Impact Test, version 6. The REE was measured by indirect calorimetry, and it was compared with the predicted REE calculated by formulas. Results: Patients with migraine had higher REE when compared to controls (p < 0.01). There was a positive correlation between REE and the patient-reported number of migraine attacks per month (Rho = 0.226; p = 0.044). Mifflin-St Jeor and Henry and Rees were the predictive formulas that have more accuracy in predicting REE in women with migraine. Discussion: Considering the benefits of nutritional interventions on treating migraines, accurately measuring REE can positively impact migraine patient care. This study enhances our understanding of the relationship between pain and energy expenditure. Our results also provide valuable insights for healthcare professionals in selecting the most effective predictive formula to calculate energy expenditure in patients with migraine.
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Neuropsychiatric or behavioral symptoms of dementia encompass a series of disorders, such as anxiety, depression, apathy, psychosis, and agitation, all commonly present in individuals living with dementia. While they are not required for the diagnosis of Alzheimer's disease (AD), they are ubiquitously present in all stages of the disease, contributing to negative clinical outcomes, including cognitive decline, functional disability, and caregiver burden. Neuropsychiatric symptoms have been conceptualized not only as risk factors but as clinical markers of decline along the AD spectrum. The concept of "mild behavioral impairment", the behavioral correlate of mild cognitive impairment, has been proposed within this framework. The first steps in the management of behavioral symptoms in AD involve defining the target and investigating potential causes and/or aggravating factors. Once these factors are addressed, non-pharmacological approaches are preferred as first-line interventions. Following the optimization of anticholinesterase treatments, specific pharmacological approaches (e.g., antidepressants, antipsychotics) can be considered weighing potential side effects.
Sintomas neuropsiquiátricos ou comportamentais de demência envolvem uma série de condições, como ansiedade, depressão, apatia, psicose e agitação, frequentemente observadas em indivíduos com demência. Embora esses sintomas não sejam necessários para o diagnóstico da doença de Alzheimer, estão presentes em todas as fases ou estágios da doença, contribuindo negativamente para o declínio cognitivo, comprometimento funcional e sobrecarga do cuidador. Os sintomas neuropsiquiátricos têm sido conceituados não apenas como fatores de risco, mas também como marcadores clínicos de progressão da doença de Alzheimer. O construto "comprometimento comportamental leve", correlato comportamental do comprometimento cognitive leve, tem sido proposto nesse contexto. Os primeiros passos na abordagem dos sintomas comportamentais da doença de Alzheimer envolvem definir os alvos-terapêuticos e investigar potenciais causas ou fatores agravantes. Após intervir nesses fatores, abordagens não farmacológicas constituem a primeira linha de intervenção. Depois da otimização do tratamento anticolinesterásico, terapias farmacológicas específicas (por exemplo, antidepressivos, antipsicóticos) podem ser consideradas, levando-se em conta potencias efeitos colaterais.
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Doença de Alzheimer , Antipsicóticos , Disfunção Cognitiva , Transtornos Mentais , Humanos , Doença de Alzheimer/psicologia , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/etiologia , Antipsicóticos/uso terapêutico , Disfunção Cognitiva/psicologia , Ansiedade , Sintomas Comportamentais/tratamento farmacológico , Sintomas Comportamentais/etiologiaRESUMO
Abstract Neuropsychiatric or behavioral symptoms of dementia encompass a series of disorders, such as anxiety, depression, apathy, psychosis, and agitation, all commonly present in individuals living with dementia. While they are not required for the diagnosis of Alzheimer's disease (AD), they are ubiquitously present in all stages of the disease, contributing to negative clinical outcomes, including cognitive decline, functional disability, and caregiver burden. Neuropsychiatric symptoms have been conceptualized not only as risk factors but as clinical markers of decline along the AD spectrum. The concept of "mild behavioral impairment", the behavioral correlate of mild cognitive impairment, has been proposed within this framework. The first steps in the management of behavioral symptoms in AD involve defining the target and investigating potential causes and/or aggravating factors. Once these factors are addressed, non-pharmacological approaches are preferred as first-line interventions. Following the optimization of anticholinesterase treatments, specific pharmacological approaches (e.g., antidepressants, antipsychotics) can be considered weighing potential side effects.
Resumo Sintomas neuropsiquiátricos ou comportamentais de demência envolvem uma série de condições, como ansiedade, depressão, apatia, psicose e agitação, frequentemente observadas em indivíduos com demência. Embora esses sintomas não sejam necessários para o diagnóstico da doença de Alzheimer, estão presentes em todas as fases ou estágios da doença, contribuindo negativamente para o declínio cognitivo, comprometimento funcional e sobrecarga do cuidador. Os sintomas neuropsiquiátricos têm sido conceituados não apenas como fatores de risco, mas também como marcadores clínicos de progressão da doença de Alzheimer. O construto "comprometimento comportamental leve", correlato comportamental do comprometimento cognitive leve, tem sido proposto nesse contexto. Os primeiros passos na abordagem dos sintomas comportamentais da doença de Alzheimer envolvem definir os alvos-terapêuticos e investigar potenciais causas ou fatores agravantes. Após intervir nesses fatores, abordagens não farmacológicas constituem a primeira linha de intervenção. Depois da otimização do tratamento anticolinesterásico, terapias farmacológicas específicas (por exemplo, antidepressivos, antipsicóticos) podem ser consideradas, levando-se em conta potencias efeitos colaterais.
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The pathophysiology of post-traumatic brain injury (TBI) behavioral and cognitive changes is not fully understood, especially in its mild presentation. We designed a weight drop TBI model in mice to investigate the role of neuroinflammation in behavioral and cognitive sequelae following mild TBI. C57BL/6 mice displayed depressive-like behavior at 72 h after mild TBI compared with controls, as indicated by a decrease in the latency to first immobility and climbing time in the forced swim test. Additionally, anxiety-like behavior and hippocampal-associated spatial learning and memory impairment were found in the elevated plus maze and in the Barnes maze, respectively. Levels of a set of inflammatory mediators and neurotrophic factors were analyzed at 6 h, 24 h, 72 h, and 30 days after injury in ipsilateral and contralateral hemispheres of the prefrontal cortex and hippocampus. Principal components analysis revealed two principal components (PC), which represented 59.1% of data variability. PC1 (cytokines and chemokines) expression varied between both hemispheres, while PC2 (neurotrophic factors) expression varied only across the investigated brain areas. Our model reproduces mild TBI-associated clinical signs and pathological features and might be a valuable tool to broaden the knowledge regarding mild TBI pathophysiology as well as to test potential therapeutic targets.
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Concussão Encefálica , Lesões Encefálicas Traumáticas , Camundongos , Animais , Concussão Encefálica/complicações , Camundongos Endogâmicos C57BL , Encéfalo/patologia , Lesões Encefálicas Traumáticas/complicações , Fatores de Crescimento Neural , Cognição , Aprendizagem em Labirinto/fisiologia , Modelos Animais de DoençasRESUMO
OBJECTIVE AND DESIGN: The present study aimed to investigate the neurochemical and behavioral effects of the acute consequences after coronavirus infection through a murine model. MATERIAL: Wild-type C57BL/6 mice were infected intranasally (i.n) with the murine coronavirus 3 (MHV-3). METHODS: Mice underwent behavioral tests. Euthanasia was performed on the fifth day after infection (5 dpi), and the brain tissue was subjected to plaque assays for viral titration, ELISA, histopathological, immunohistochemical and synaptosome analysis. RESULTS: Increased viral titers and mild histological changes, including signs of neuronal degeneration, were observed in the cerebral cortex of infected mice. Importantly, MHV-3 infection induced an increase in cortical levels of glutamate and calcium, which is indicative of excitotoxicity, as well as increased levels of pro-inflammatory cytokines (IL-6, IFN-γ) and reduced levels of neuroprotective mediators (BDNF and CX3CL1) in the mice brain. Finally, behavioral analysis showed impaired motor, anhedonia-like and anxiety-like behaviors in animals infected with MHV-3. CONCLUSIONS: In conclusion, the data presented emulate many aspects of the acute neurological outcomes seen in patients with COVID-19. Therefore, this model may provide a preclinical platform to study acute neurological sequelae induced by coronavirus infection and test possible therapies.
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COVID-19 , Vírus da Hepatite Murina , Humanos , Animais , Camundongos , Camundongos Endogâmicos C57BL , Vírus da Hepatite Murina/metabolismo , Citocinas/metabolismo , COVID-19/patologia , Encéfalo/metabolismoRESUMO
Bovine alpha herpesvirus-5 (BoAHV-5) is related to the development of meningoencephalitis in cattle. Very little is known about the molecular pathways involved in the central nervous system (CNS) damage associated with inflammation during BoHV-5 infection in mice. To better identify the specific immunological pathways triggered by BoAHV-5 infection in mice, we evaluated the mRNA expression of 84 genes involved in innate and adaptive immune responses. We compared gene expression changes in the cerebrum from noninfected and infected mice with BoHV-5 at a 1 × 107 TCID50. Then, we analyzed the association of these genes with neurological signs, neuropathology, and activation of glial cells in response to BoHV-5 infection. Three days after BoAHV-5 infection, increased expression of TNF, IL-2, CXCL10, CXCR3, CCR4, CCL5, IFN-γ, IL-10, IRF7, STAT1, MX1, GATA 3 C3, LIZ2, caspase-1 and IL-1b was found. We also observed the upregulated expression of the CD8a, TBX21 and CD40LG genes and the downregulated expression of the CD4 gene after BoAHV-5 infection. In addition, BoHV-5-infected animals showed higher levels of all the evaluated inflammatory mediators (TNF, IFN-γ and IL-10) on day 3 postinfection. BoAHV-5-infected animals showed neurological changes along with meningoencephalitis, neuropil vacuolation, hemorrhage and reactive gliosis. Astrogliosis and microgliosis, indicated by increased expression of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba-1), were found throughout the neuropil in infected brains. Moreover, cleaved caspase-3 immunopositive glio-inflammatory cells were visualized around some blood vessels in areas of neuroinflammation in the cerebrum. In agreement on that we found higher cleaved caspase-3 and Iba-1 expression evaluated by western blot analysis in the brains of infected mice compared to control mice. In conclusion, our results revealed.
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BACKGROUND: Parkinsonism is strongly associated with ageing, and many studies have suggested that parkinsonian signs may affect up to half of older adults and is associated with a wide range of adverse health outcomes. We compared clinical and functional characteristics of oldest-old community-dwelling individuals with parkinsonism (parkinsonian group [PG]) to individuals without parkinsonism (non-parkinsonian group [NPG]. METHODS: The Pietà study is a population-based study conducted in Caeté, southeast Brazil, involving 607 individuals aged 75 + years submitted to an extensive clinical evaluation. A subset of 65 PG individuals (61.5% women, median age of 82 years) was compared to 542 NPG individuals (64.8% women, median age of 80 years). RESULTS: PG individuals had significantly more functional impairment, clinical comorbidities (including number of falls, loss of bladder control and dysphagia) and major depression. Multivariate analysis revealed that older age, higher UPDRSm scores, lower category fluency test (animals/minute) and delayed recall memory scores were associated with PG. This group was also more cognitively impaired, with lower performance than NPG individuals in the Mini-Mental State Examination, category fluency test (animals/minute), clock drawing and in delayed recall (p < 0.001 for all tests). UPDRSm scores were the most contributing factor to cognition that independently explained variability in functionality of the entire sample. CONCLUSION: Individuals aged 75 + years with parkinsonism were significantly more clinically and functionally impaired in this population-based sample. Cognitive dysfunction explained most of the loss of functionality in these patients. UPDRS-m scores contributed independently to explain variability in functionality in the whole sample.
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Disfunção Cognitiva , Transtornos Parkinsonianos , Feminino , Animais , Masculino , Transtornos Parkinsonianos/epidemiologia , Envelhecimento , Brasil/epidemiologia , CogniçãoRESUMO
BACKGROUND: Cognitive and functional decline are common problems in older adults, especially in those 75+ years old. Currently, there is no specific plasma biomarker able to predict this decline in healthy old-age people. Machine learning (ML) is a subarea of artificial intelligence (AI), which can be used to predict outcomes Aim: This study aimed to evaluate routine laboratory variables able to predict cognitive and functional impairment, using ML algorithms, in a cohort aged 75+ years, in a one-year follow-up study. METHOD: One hundred and thirty-two older adults aged 75+ years were selected through a community-health public program or from long-term-care institutions. Their functional and cognitive performances were evaluated at baseline and one year later using a functional activities questionnaire, Mini-Mental State Examination, and the Brief Cognitive Screening Battery. Routine laboratory tests were performed at baseline. ML algorithms-random forest, support vector machine (SVM), and XGBoost-were applied in order to describe the best model able to predict cognitive and functional decline using routine tests as features. RESULTS: The random forest model showed better accuracy than other algorithms and included triglycerides, glucose, hematocrit, red cell distribution width (RDW), albumin, hemoglobin, globulin, high-density lipoprotein cholesterol (HDL-c), thyroid-stimulating hormone (TSH), creatinine, lymphocyte, erythrocyte, platelet/leucocyte (PLR), and neutrophil/leucocyte (NLR) ratios, and alanine transaminase (ALT), leukocyte, low-density lipoprotein cholesterol (LDL-c), cortisol, gamma-glutamyl transferase (GGT), and eosinophil as features to predict cognitive decline (accuracy = 0.79). For functional decline, the most important features were platelet, PLR and NLR, hemoglobin, globulin, cortisol, RDW, glucose, basophil, B12 vitamin, creatinine, GGT, ALT, aspartate transferase (AST), eosinophil, hematocrit, erythrocyte, triglycerides, HDL-c, and monocyte (accuracy = 0.92). CONCLUSIONS: Routine laboratory variables could be applied to predict cognitive and functional decline in oldest-old populations using ML algorithms.
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Very few studies have investigated cognition and impulsivity following mild traumatic brain injury (mTBI) in the general population. Furthermore, the neurobiological mechanisms underlying post-TBI neurobehavioral syndromes are complex and remain to be fully clarified. Herein, we took advantage of machine learning based-modeling to investigate potential biomarkers of mTBI-associated impulsivity. Twenty-one mTBI patients were assessed within one-month post-TBI and their data were compared to 19 healthy controls on measures of impulsivity (Barratt Impulsiveness Scale - BIS), executive functioning, episodic memory, self-report cognitive failures and blood biomarkers of inflammation, vascular and neuronal damage. mTBI patients were significantly more impulsive than controls in BIS total and subscales. Serum levels of sCD40L, Cathepsin D, IL-4, Neuropilin-1, IFN-α2, and Copeptin were associated with impulsivity in mTBI patients. Besides showing that mTBI are associated with impulsivity in non-military people, we unveiled different pathophysiological pathways potentially implicated in mTBI-related impulsivity.
Assuntos
Concussão Encefálica , Humanos , Concussão Encefálica/complicações , Projetos Piloto , Comportamento Impulsivo/fisiologia , Biomarcadores , Função ExecutivaRESUMO
Objectives: Bipolar disorder type 1 (BD1) and behavioral-variant frontotemporal dementia (bvFTD) share similar behavioral and cognitive symptoms, rendering the differential diagnosis between them a clinical challenge. We investigated the accuracy of social cognition (SC) measures to differentiate bvFTD from BD. Methods: We included three groups of participants: early-onset BD1 (in remission, n=20), bvFTD (n=18), and cognitively healthy controls (HC) (n=40), matched for age, schooling, and sex. All participants underwent cognitive assessment, including the Facial Emotion Recognition (FER) and Modified Faux-Pas (mFP) tests, which assess mentalizing. Results: Compared to HC, BD1 and bvFTD patients underperformed on both SC measures. BD1 and bvFTD did not differ regarding FER or mFP total scores, although patients with bvFTD had significantly higher difficulties than those in the BD1 group to detect social faux-pas (p < 0.001, d = 1.35). Conclusion: BD1 and bvFTD share deficits in the core SC functions. These findings should be considered in the development of tasks aiming to improve clinical differentiation between the two disorders.