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1.
J Neuroimmunol ; 345: 577270, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32480241

RESUMO

The purpose of current study was to evaluate the effect of curcumin (CUR) loaded lipid-core nanocapsules (CUR-LNC) treatment on neuroinflammatory and behavioral alterations in a model of sickness behavior induced by lipopolysaccharide (LPS) in rats. Rats were treated with CUR-LNC and CUR daily for 14 days. After the last treatments, sickness behavior was induced with LPS. Sickness behavior LPS-induced was confirmed by behavioral tests, an increase in levels of proinflammatory cytokines, decrease in levels of IL-10, overexpression of IDO-1 and IDO-2. In conclusion, CUR-LNC treatment attenuated the neuroinflammatory and behavioral changes caused in sickness behavior model.


Assuntos
Curcumina/administração & dosagem , Comportamento de Doença/fisiologia , Mediadores da Inflamação/imunologia , Lipopolissacarídeos/toxicidade , Locomoção/fisiologia , Nanocápsulas/administração & dosagem , Animais , Portadores de Fármacos/administração & dosagem , Comportamento de Doença/efeitos dos fármacos , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Lipídeos , Locomoção/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar
2.
Biol Res Nurs ; 22(1): 92-102, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31601118

RESUMO

Infections in older individuals can result in cognitive function decline, yet research is limited on how recurrent infections affect cognitive responses. Activation of the immune system results in sickness responses mediated by cytokines. This pilot study examined effects of a model of recurrent infection in aged, male Brown Norway rats on sickness responses, including spatial learning, and cytokine levels. To model initial and recurrent infection, 300 µg/kg lipopolysaccharide (LPS) or saline was administered 1/day for 2 consecutive days during 2 weeks separated by 16 days. Testing occurred for 6 days during each LPS injection week using the Morris water maze, a measure used to evaluate spatial learning. Directional heading error (DHE) and swim time latency served as spatial learning indices. Retention tests and probe trials assessed memory. Plasma cytokine levels were assessed 5 and 24 hr after each LPS injection during Week 2. While food intake and weight decreased significantly in LPS-injected rats compared to controls during Week 1, both displayed increased DHE. Despite exhibiting lessened sickness behaviors during Week 2, experimental animals still displayed spatial learning deficits. Probe trials revealed memory deficits in LPS-injected animals. Interleukin 6 level was higher in the experimental group 5 and 24 hr after LPS injection on Day 1 compared to Day 2 and higher in the experimental compared to the control group at 5 hr on Day 1. Cognitive effects were dissociated from metabolic effects in aged rats, with recurring LPS exposure resulting in persistent cognitive impairment despite decreased sickness responses. Further research with older individuals is warranted.


Assuntos
Comportamento de Doença/efeitos dos fármacos , Interleucina-6/efeitos adversos , Interleucina-6/farmacologia , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/efeitos adversos , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/fisiopatologia , Aprendizagem Espacial/efeitos dos fármacos , Fatores Etários , Animais , Comportamento de Doença/fisiologia , Masculino , Aprendizagem em Labirinto/fisiologia , Projetos Piloto , Ratos , Aprendizagem Espacial/fisiologia
3.
Dev Psychobiol ; 62(3): 400-408, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31489628

RESUMO

BACKGROUND: Early life stress (ELS) has been linked to health disparities across the human lifespan, particularly increased risk for depression and its recurrence. In this study we explore two plausible and competing pathways through which ELS may lead to depression via inflammation. METHODS: Participants (ages 18-22; n = 41) completed the Early Trauma Inventory as a measure of ELS. Participants then completed consecutive daily diaries of mood and other sickness behavior for the 7 days prior to and 7 days after receiving the annual influenza vaccine. Circulating concentrations of plasma interleukin-6 (IL-6) were measured immediately before and 24 hr after vaccination. RESULTS: ELS was not associated with the magnitude of change in IL-6 from pre- to post-vaccine, however, exposure to ELS moderated the association between change in IL-6 from pre- to post-vaccine and changes in both cognitive difficulty and depressed mood. Individuals exposed to greater ELS showed greater psychological sensitivity to increases in IL-6. CONCLUSIONS: Exposure to ELS may increase sensitivity to peripheral inflammation in the central nervous system. Future studies elaborating on the impact of ELS on the sensitivity of specific neural circuits and cells to inflammation are needed.


Assuntos
Atenção , Cognição , Depressão/sangue , Comportamento de Doença , Inflamação/sangue , Interleucina-6/sangue , Estresse Psicológico/sangue , Adolescente , Adulto , Atenção/fisiologia , Cognição/fisiologia , Feminino , Humanos , Comportamento de Doença/fisiologia , Vacinas contra Influenza/imunologia , Masculino , Adulto Jovem
4.
Psychosom Med ; 81(8): 711-719, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31600173

RESUMO

OBJECTIVE: Social relationships can both influence and be influenced by immune processes. Past work implicates two distinct pathways along which this interaction may occur: inflammatory processes and antiviral processes. This article reviews how social behavior is modulated by these two immune processes and how such processes may in turn regulate social behavior. METHODS: This narrative review outlines existing work on social behavior and both inflammatory and antiviral processes. We propose an evolutionary framework that aims to integrate these findings. Specifically, social isolation has evolutionarily increased the likelihood of wounding and therefore increased the need for inflammation, which works to promote healing. Conversely, broader social networks provide protection from physical threats but also lead to increased pathogen exposure, necessitating a more robust antiviral response. RESULTS: This review highlights that social adversity, such as social exclusion or loneliness, is associated with increased inflammation, whereas social contact is associated with increased antiviral immunity. Furthermore, increased inflammation leads to sensitivity to social stimuli, presumably to avoid hostile conspecifics and approach allies who may provide care while vulnerable. Individuals with inadequate antiviral immunity engage in behaviors that minimize pathogen exposure, such as reduced affiliative behavior. CONCLUSIONS: This review suggests that adverse social experiences (social isolation, perceived social threat) may induce inflammatory responses while suppressing antiviral immunity, whereas positive experiences of social connection may reduce inflammation and bolster antiviral responses. Although acutely elevated inflammation would be adaptive under conditions where wounding is likely, chronic inflammation related to continued social adversity may have detrimental health consequences.


Assuntos
Inflamação/imunologia , Relações Interpessoais , Modelos Imunológicos , Comportamento Social , Determinantes Sociais da Saúde , Viroses/imunologia , Evolução Biológica , Doença Crônica , Suscetibilidade a Doenças/imunologia , Transmissão de Doença Infecciosa/prevenção & controle , Emoções/fisiologia , Retroalimentação Fisiológica , Humanos , Comportamento de Doença/fisiologia , Inflamação/psicologia , Neuroimunomodulação/fisiologia , Seleção Genética , Isolamento Social/psicologia , Percepção Social , Viroses/prevenção & controle , Viroses/psicologia , Viroses/transmissão , Ferimentos e Lesões/imunologia , Ferimentos e Lesões/psicologia
5.
Exp Gerontol ; 127: 110717, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31479727

RESUMO

Individual differences in premorbid behaviors and in those exhibited in the course of an infection disease may be useful to explain the individual susceptibility to infections, the underlying neuroimmunological mechanisms and be helpful to design patient oriented treatments with better prediction of pharmacological reactivity/outcome. Age (old) and gender (male) are also considered vulnerability factors. In the present study, the motor, emotional, anxious-like and social phenotypes of adult (6-month-old) and old (18-month-old) male C57BL/6 × 129Sv mice were determined using both a transversal and longitudinal designs prior to the analysis of LPS (150 mg/kg, i.p.)-induced sickness behavior and mortality. The results show: i) Individual premorbid behavioral phenotype had short- and long-term predictive value of hours of survival; ii) Persistence of behavioral traits from adulthood to old age and predictive value on hours of survival; iii) First signs of sickness behavior were also predicting mortality, mostly in old animals; iv) LPS-sickness behavior was the same at both ages but adult animals were able to show attempts of motor recovery; v) The mortality rate over 96 h was 100% in both ages, but old animals showed shorter survival times. In summary, these results confirm the relevance of age/aging but also individual behavioral differences in the premorbid phenotype and the morbidity response to the LPS-induced-sepsis that correlate with the individual's mortality. Thus, this work supports the translational scenarios to study personalized evaluation of risks factors and psycho-neuro-immunological mechanisms relevant for better interventions and prognosis in the critically ill young but specially aged patient population.


Assuntos
Comportamento Animal/fisiologia , Comportamento de Doença/fisiologia , Sepse/mortalidade , Animais , Peso Corporal/fisiologia , Lipopolissacarídeos/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Atividade Motora/fisiologia , Fenótipo , Sepse/psicologia , Comportamento Social
6.
Epilepsy Behav ; 98(Pt A): 210-219, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31382179

RESUMO

OBJECTIVES: The study aimed to investigate if South African individuals with psychogenic nonepileptic seizures (PNES) differ from individuals with epileptic seizures (ES) and other nonepileptic seizures (oNES) in terms of demographic and seizure characteristics, personality traits, illness behaviors, and depression, anxiety, and posttraumatic stress disorder (PTSD) comorbidity in statistically significant ways; and if so, to test if these differences can be utilized in raising suspicion of PNES as the differential diagnosis to epilepsy and oNES in practice. METHODS: Data were analyzed from 29 adults with seizure complaints recruited using convenience sampling from a private and a government hospital with video-electroencephalography (vEEG) technology. A quantitative double-blind convenient sampling comparative design was used. A demographic and seizure questionnaire, the NEO Five Factor Inventory-3 (NEO-FFI-3), an abbreviated version of Illness Behavior Questionnaire (IBQ), and the Beck Anxiety Inventory - Primary Care (BAI-PC) were administered. Cronbach's alphas, analysis of variance (ANOVA), cross-tabulation, Fisher exact test, and receiver operating characteristic (ROC) analyses were performed on the dataset. RESULTS: The total sample consisted of 29 participants, of which 5 had PNES (17%), 21 ES (73%), and 3 oNES (10%). The final sample was comprised of 24 participants from the private hospital and 5 from the government hospital. The group with PNES was found to be significantly more male, to experience significantly more monthly seizures, and chronic pain when comparing the PNES with the ES group, and the PNES with the combined ES and oNES group in both private only sample, as well as the private and government hospital combined sample. Patients with PNES also had a higher level of education compared with the group with ES in the combined private and government hospital sample, something that was not evident in the private hospital only sample. No significant differences between groups were found in either sample in terms of age, population group, language, age at first seizure, and the NEO-FFI-3 subscales. All three groups scored above the cutoff point of 5 exhibiting depression, anxiety, and PTSD symptoms on the BAI-PC in both samples. However, the group with PNES tended to score significantly higher than the group with ES and the combined ES and oNES group in the private hospital sample. A cutoff point of 12 on the BAI-PC was found to predict PNES in this seizure population with 80% sensitivity and 89% specificity. However, once the analysis was repeated on the combined private and government hospital sample, significance in BAI-PC scores between groups was lost. All scales showed good reliability in our study, with the exception of the "Openness to Experience" subscale of the NEO-FFI-3 once reliability analysis was carried out on the combined private and government hospital group. CONCLUSIONS: This study provides an important stepping stone in the understanding of demographic and seizure factors, personality domains, abnormal illness behaviors, and psychiatric comorbidity in the South African population with PNES. The study also reported on a cutoff score of 12 on the BAI-PC predicting PNES with 80% sensitivity and 89% specificity in a private hospital sample.


Assuntos
Epilepsia/psicologia , Comportamento de Doença , Transtornos Mentais/psicologia , Personalidade , Convulsões/psicologia , Adulto , Comorbidade , Diagnóstico Diferencial , Método Duplo-Cego , Eletroencefalografia/métodos , Epilepsia/diagnóstico , Epilepsia/epidemiologia , Feminino , Humanos , Comportamento de Doença/fisiologia , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Personalidade/fisiologia , Testes de Personalidade , Reprodutibilidade dos Testes , Convulsões/diagnóstico , Convulsões/epidemiologia , Inquéritos e Questionários , Adulto Jovem
7.
Neurotherapeutics ; 16(4): 1335-1349, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31338703

RESUMO

Neuropeptide Y (NPY) has been demonstrated to exert stress buffering effects and promote resilience. Non-invasive intranasal (IN) application of NPY to rodents is able to mitigate traumatic stress-induced behavioral changes as well as dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. However, it is unknown whether IN NPY could prevent the behavioral, pro-inflammatory and neurochemical responses to peripheral immune activation by the Toll-like receptor 4 (TLR4) stimulant lipopolysaccharide (LPS). Therefore, we analyzed the effects of IN NPY (100 µg) on the behavioral sickness response (reduced locomotion and exploration) and the underlying molecular mechanisms, 3 h and 21 h after intraperitoneal injections of LPS (0.03 mg/kg) in male C57BL/6N mice. The acute behavioral sickness response was significantly dampened by pretreatment with IN NPY 3 h after LPS injection. This effect was accompanied by diminished weight loss and lowered plasma corticosterone (CORT) levels 21 h after LPS injection. In contrast, acute circulating cytokine levels and hypothalamic cytokine mRNA expression remained unaltered by IN NPY, which indicates that the peripheral and cerebral immune response to LPS was left undisturbed. Our findings are in agreement with the reported activity of NPY to dampen the response of the HPA axis to stress. We propose that IN NPY ablates sickness behavior at a site beyond the peripheral and cerebral cytokine response, an action that is associated with reduced activity of the HPA axis as determined by decreased plasma CORT.These results indicate that IN NPY administration may be relevant to the management of neuropsychiatric disorders arising from immune-induced neuroendocrine dysfunction.


Assuntos
Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Comportamento de Doença/efeitos dos fármacos , Imunidade Celular/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Neuropeptídeo Y/administração & dosagem , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Administração Intranasal , Animais , Corticosterona/sangue , Corticosterona/imunologia , Sistema Hipotálamo-Hipofisário/imunologia , Sistema Hipotálamo-Hipofisário/metabolismo , Comportamento de Doença/fisiologia , Imunidade Celular/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sistema Hipófise-Suprarrenal/imunologia , Sistema Hipófise-Suprarrenal/metabolismo
8.
Health Psychol ; 38(7): 648-657, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31120269

RESUMO

OBJECTIVE: Illness behaviors-or responses to bodily symptoms-predict individuals' recovery and functioning; however, there has been little research on the early life personality antecedents of illness behavior. This study's primary aims were to evaluate (a) childhood temperament traits (i.e., emotionality and sociability) as predictors of adult illness behaviors, independent of objective health; and (b) adult temperament traits for mediation of childhood temperament's associations. METHOD: Participants included 714 (53% male; 350 adoptive family and 364 control family) children and siblings from the Colorado Adoption Project (CAP; Plomin & DeFries, 1983). Structural regression analyses evaluated paths from childhood temperament to illness behavior (i.e., somatic complaints, sick days, and medication use) at two adulthood assessments (CAP years 21 and 30). Analyses controlled for participant age, sex, family type (adoptive or control), adopted status, parent education/occupation, and middle childhood illnesses, doctor visits, and life events stress. RESULTS: Latent illness behavior factors were established across 2 adulthood assessments. Multilevel path analyses revealed that higher emotionality (fearfulness) in adulthood-but not childhood temperament-predicted higher levels of illness behavior at both assessments. Lastly, lower emotionality-fearfulness partially mediated the effect of higher childhood sociability on adult illness behavior. CONCLUSIONS: Results suggest the importance of childhood illness experiences and adult emotionality (fearfulness) in shaping illness behavior in early adulthood. They also suggest a small, protective role of childhood sociability on reduced trait fearfulness in adulthood. These findings broaden our understanding of the prospective links between temperament and illness behavior development, suggesting distinct associations from early life illness experiences. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Comportamento Infantil/psicologia , Efeitos Psicossociais da Doença , Comportamento de Doença , Temperamento , Adulto , Criança , Feminino , Humanos , Comportamento de Doença/fisiologia , Comportamento Impulsivo/fisiologia , Estudos Longitudinais , Masculino , Relações Pais-Filho , Personalidade/fisiologia , Estudos Prospectivos , Temperamento/fisiologia , Adulto Jovem
9.
J Neuroinflammation ; 16(1): 40, 2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-30777093

RESUMO

BACKGROUND: Ischemic stroke results in a robust inflammatory response within the central nervous system. As the immune-inhibitory CD200-CD200 receptor 1 (CD200R1) signaling axis is a known regulator of immune homeostasis, we hypothesized that it may play a role in post-stroke immune suppression after stroke. METHODS: In this study, we investigated the role of CD200R1-mediated signaling in stroke using CD200 receptor 1-deficient mice. Mice were subjected to a 60-min middle cerebral artery occlusion and evaluated at days 3 and 7, representing the respective peak and early resolution stages of neuroinflammation in this model of ischemic stroke. Infarct size and behavioral deficits were assessed at both time points. Central and peripheral cellular immune responses were measured using flow cytometry. Bacterial colonization was determined in lung tissue homogenates both after acute stroke and in an LPS model of systemic inflammation. RESULTS: In wild-type (WT) animals, CD200R1 was expressed on infiltrating monocytes and lymphocytes after stroke but was absent on microglia. Early after ischemia (72 h), CD200R1-knockout (KO) mice had significantly poorer survival rates and an enhanced susceptibility to spontaneous bacterial colonization of the respiratory tract compared to wild-type (WT) controls, despite no difference in infarct or neurological deficits. While the CNS inflammation was resolved by day 7 post-stroke in WT mice, brain-resident microglia and monocyte activation persisted in CD200R1-KO mice, accompanied by a delayed, augmented lymphocyte response. At this time point, CD200R1-KO mice displayed greater weight loss, more severe neurological deficits, and impaired motor function compared to WT. Systemically, CD200R1-KO mice exhibited signs of persistent infection including lymphopenia, T cell activation and memory conversion, and narrowing of the TCR repertoire. These findings were confirmed in a second model of acute neuroinflammation induced by systemic endotoxin challenge. CONCLUSION: This study defines an essential role of CD200-CD200R1 signaling in stroke. Loss of CD200R1 led to high mortality, increased rates of post-stroke infection, and enhanced entry of peripheral leukocytes into the brain after ischemia, with no increase in infarct size. This suggests that the loss of CD200 receptor leads to enhanced peripheral inflammation that is triggered by brain injury.


Assuntos
Antígenos CD/metabolismo , Infecções Bacterianas/etiologia , Encefalite/etiologia , Infarto da Artéria Cerebral Média/fisiopatologia , Receptores de Orexina/metabolismo , Recuperação de Função Fisiológica/fisiologia , Transdução de Sinais/fisiologia , Animais , Encéfalo/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/fisiologia , Comportamento de Doença/efeitos dos fármacos , Comportamento de Doença/fisiologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Atividade Motora/fisiologia , Comportamento de Nidação/fisiologia , Receptores de Orexina/genética , Fagocitose/fisiologia , Transtornos Psicomotores/etiologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
10.
Psychopharmacology (Berl) ; 236(10): 2975-2982, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30806746

RESUMO

RATIONALE: While the relationship between inflammation and depression is well-established, the molecular mechanisms mediating this relationship remain unclear. RNA sequencing analysis comparing brains of vehicle- and lipopolysaccharide-treated mice revealed LCN2 among the most dysregulated genes. As LCN2 is known to be an important regulator of the immune response to bacterial infection, we investigated its role in the behavioral response to lipopolysaccharide. OBJECTIVE: To explore the role of LCN2 in modulating behavior following lipopolysaccharide administration using wild type (WT) and lcn2-/- mice. METHODS: Using a within-subjects design, mice were treated with 0.33 mg/kg liposaccharide (LPS) and vehicle. Primary outcome measures included body weight, food consumption, voluntary wheel running, sucrose preference, and the tail suspension test. To evaluate the inflammatory response, 1 week later, mice were re-administered either vehicle or LPS and terminated at 6 h. RESULTS: While lcn2-/- mice had increased baseline food consumption and body weight, they showed a pattern of reduced food consumption and weight loss similar to WT mice in response to LPS. WT and lcn2-/- mice both recovered voluntary activity on the fourth day following LPS. LPS induced equivalent reductions in sucrose preference and TST immobility in the WT and lcn2-/- mice. Finally, there were no significant effects of genotype on inflammatory markers. CONCLUSIONS: Our data demonstrate that lcn2 is dispensable for sterile inflammation-induced sickness and depression-like behavior. Specifically, lcn2-/- mice displayed sickness and immobility in the tail suspension test comparable to that of WT mice both in terms of intensity and duration.


Assuntos
Depressão/induzido quimicamente , Depressão/metabolismo , Comportamento de Doença/fisiologia , Lipocalina-2/deficiência , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/imunologia , Encéfalo/metabolismo , Citocinas/metabolismo , Depressão/imunologia , Comportamento de Doença/efeitos dos fármacos , Inflamação/induzido quimicamente , Inflamação/imunologia , Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia
11.
Brain Behav Immun ; 79: 186-194, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30716391

RESUMO

It is well-established that bacterial lipopolysaccharides (LPS) can promote neuroinflammation through receptor Toll-like 4 activation and induces sickness behavior in mice. This phenomenon triggers changes in membranes lipid dynamics to promote the intracellular cell signaling. Desorption electrospray ionization mass spectrometry (DESI-MS) is a powerful technique that can be used to image the distribution of lipids in the brain tissue directly. In this work, we characterize the LPS-induced neuroinflammation and the lipid dynamics in C57BL/6 mice at 3 and 24 h after LPS injection. We have observed that intraperitoneal administration of LPS (5 mg/kg body weight) induces sickness behavior and triggers a peripheral and cerebral increase of pro- and anti-inflammatory cytokine levels after 3 h, but only IL-10 was upregulated after 24 h. Morphological analysis of hypothalamus, cortex and hippocampus demonstrated that microglial activation was present after 24 h of LPS injection, but not at 3 h. DESI-MS revealed a total of 14 lipids significantly altered after 3 and 24 h and as well as their neuroanatomical distribution. Multivariate statistical analyzes have shown that ions associated with phosphatidylethanolamine [PE(38:4)] and docosatetraenoic acid [FA (22:4)] could be used as biomarkers to distinguish samples from the control or LPS treated groups. Finally, our data demonstrated that monitoring cerebral lipids dynamics and its neuroanatomical distribution can be helpful to understand sickness behavior and microglial activation after LPS administration.


Assuntos
Lipídeos/imunologia , Inflamação Neurogênica/imunologia , Neuroimunomodulação/imunologia , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Citocinas/metabolismo , Hipocampo/diagnóstico por imagem , Hipocampo/metabolismo , Hipotálamo/diagnóstico por imagem , Hipotálamo/metabolismo , Comportamento de Doença/fisiologia , Lipopolissacarídeos/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/imunologia , Transdução de Sinais , Espectrometria de Massas por Ionização por Electrospray/métodos
12.
Psychopharmacology (Berl) ; 236(6): 1829-1838, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30666359

RESUMO

RATIONALE AND OBJECTIVES: Cannabinoid receptor 2 (CB2R) signaling in the brain is associated with the pathophysiology of depression. Sickness behavior, characterized by lessened mobility, social interaction, and depressive behavior, is linked with neuroinflammation, oxidative stress, and immune system. The present study was aimed at evaluating 1-phenylisatin (PI), a CB2R agonist, in sickness behavior. METHODS: Influence of acute and 7-day activation of CB2R using PI in lipopolysaccharide (LPS)-induced sickness behavior was assessed in mice. An acute injection of LPS (1.5 mg/kg) produced a fully developed sickness behavior in animals within 1 h of administration. The behavioral paradigm was assessed by open field test, forced swim test, and tail suspension test. Further, tumor necrosis factor-α (TNF-α), antioxidant enzymes, and lipid peroxidation were measured in the brain to correlate neuroinflammation and oxidative stress with sickness behavior. Both treatments, PI (20 mg/kg) and imipramine (15 mg/kg), were administered orally (once for acute and once daily for 7-day protocols). RESULTS: LPS elevated the brain TNF-α level, augmented oxidative stress, and induced the sickness behavior in mice. Acute and 7-day treatment of mice with PI significantly reduced the LPS-induced sickness behavior. In addition, PI inhibited the neuroinflammation evidenced by a reduction in brain TNF-α and oxidative stress. CONCLUSION: Our data propose that acute and long-term activation of CB2R might prevent neuroinflammation and oxidative stress-associated sickness behavior.


Assuntos
Encéfalo/metabolismo , Comportamento de Doença/fisiologia , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , Estresse Oxidativo/fisiologia , Receptor CB2 de Canabinoide/metabolismo , Animais , Antioxidantes/metabolismo , Encéfalo/efeitos dos fármacos , Canabinoides/agonistas , Canabinoides/metabolismo , Elevação dos Membros Posteriores/efeitos adversos , Elevação dos Membros Posteriores/fisiologia , Elevação dos Membros Posteriores/psicologia , Comportamento de Doença/efeitos dos fármacos , Mediadores da Inflamação/antagonistas & inibidores , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Distribuição Aleatória , Receptor CB2 de Canabinoide/agonistas , Fator de Necrose Tumoral alfa/metabolismo
13.
Neuroimmunomodulation ; 26(6): 285-291, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31935743

RESUMO

OBJECTIVE: Previously we observed an attenuation of body temperature in lactating rats treated with lipopolysaccharide (LPS) compared with virgin saline-treated females. We proposed that high levels of prolactin (PRL) during lactation may induce this attenuation because PRL has a suppressive effect on inflammation. In the present study, we induced hyperprolactinemia in female virgin rats to investigate the effects of PRL on body temperature and sickness behavior induced by LPS. METHODS: To induce hyperprolactinemia, female rats in the estrous phase received domperidone 3 times/day for 5 days and an LPS injection (D + LPS group). Two other groups were treated with saline solution for 5 days, and one of them received a saline injection (S + S group) and the other LPS (S + LPS group). Tympanic temperature was assessed 0, 2, 4, 6, 8, 10, 24, 48, 72, and 96 h after treatment. Body weight gain and food and water consumption were observed 24, 48, 72, and 96 h after treatment. RESULTS: Hyperprolactinemia impaired LPS-induced hypothermia and hyperthermia phases of body temperature. Body weight gains in the S + LPS group and the D + LPS group were similar. A decrease in food consumption was observed in the D + LPS rats at 72 and 96 h compared to the S + LPS group. CONCLUSION: Hyperprolactinemia impaired the body temperature increase induced by LPS and several signs of sickness behavior, suggesting that febrile responses to LPS can be modulated by the physiological state. These phenomena may have adaptive value for reproduction.


Assuntos
Temperatura Corporal/efeitos dos fármacos , Hiperprolactinemia , Comportamento de Doença/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Animais , Temperatura Corporal/fisiologia , Feminino , Comportamento de Doença/fisiologia , Ratos , Ratos Wistar
14.
Physiol Behav ; 198: 76-83, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30290182

RESUMO

Poor health is associated with an increased risk of tail biting outbreaks in pigs. We propose that this is because illness changes social dynamics either by changing the behaviour of the sick pig towards its penmates, the behaviour of the healthy penmates towards the sick pig, or both. We tested the effect of immune stimulation (lipopolysaccharide (LPS) injection: O111:B4; 1.5 µg kg-1 IV) on social behaviour in gilts housed in triplets in a cross-over experiment. Each pen was subjected to the control treatment (all three pigs injected with saline) and then LPS treatment (one pig injected with LPS, two injected with saline), or vice versa. LPS injected pigs had a shift in social motivation and performed more tail- and ear- directed behaviour than saline pigs two days after injection. They seemed to fit the description of 'sick and grumpy'. This change was seen about 40 h after the signs of acute illness dissipated and was not accompanied by a similar increase in activity. We discuss possible mechanisms for this behavioural change in light of changes in neurotransmitter levels at three days after LPS injection described in a previous experiment.


Assuntos
Comportamento Animal/fisiologia , Comportamento de Doença/fisiologia , Lipopolissacarídeos , Comportamento Social , Criação de Animais Domésticos , Animais , Feminino , Suínos
15.
Sci Rep ; 8(1): 16682, 2018 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-30420741

RESUMO

When infected, animals change their behaviors in several ways, including by decreasing their activity, their food and water intake, and their interest in social interactions. These behavioral alterations are collectively called sickness behaviors and, for several decades, the main hypotheses put forward to explain this phenomenon were that engaging in sickness behaviors facilitated the fever response and improved the likelihood of host survival. However, a new hypothesis was recently proposed suggesting that engaging in sickness behaviors may serve to protect kin. We tested this kin protection hypothesis by combining a field and a laboratory experiment in house mice. In both experiments, we induced sickness behaviors by administration of a pro-inflammatory agent. In the field experiment, we then collected genetic data and assessed whether relatedness affected the intensity of sickness behaviors. In the lab experiment, we manipulated relatedness in small social groups and assessed whether having a closely related individual (a sibling) in the group altered social interactions or visits to common resources (such as food and water containers) once immune-challenged. Our results do not support the kinship protection hypothesis and therefore advance our understanding of why such an apparently costly set of behavioral changes would be evolutionarily maintained.


Assuntos
Comportamento Animal/fisiologia , Comportamento de Doença/fisiologia , Animais , Modelos Animais de Doenças , Feminino , Febre/fisiopatologia , Masculino , Camundongos , Comportamento Social
17.
Biomed Pharmacother ; 108: 1535-1545, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30372855

RESUMO

Sickness behaviour, fever, anxiety, anorexia and depression are interrelated phenomena. The citrus fruit peels offering significant low-cost nutritional dietary supplements due to its rejuvenating biological activities. The present study was undertaken to explore the beneficial effect of enriched phenolic fraction of peel (PFMC) in lipopolysaccharide (LPS)-induced sickness behaviour and anorexia in mice. Further, the HPTLC estimation of hesperidin, total phenolic and flavonoid content in PFMC were carried out. In silico molecular docking and dynamic studies of bioactive compounds against NF-κB (1NFK) were also performed. The amount of hesperidin was found to be 55.33 mg/g of PFCM as per the proposed HPTLC method. Total phenolic and flavonoid content was found to be 71 mg of gallic acid/g and 58.1 mg of quercetin/g of PFCM. The single dose of LPS (400 µg/kg, i.p) treatment exhibited significant reduction in food, water intake and behavioural tests and tissue GSH, whereas significantly higher levels of tissue LPO and plasma IL-6 levels compared to normal control. Pre-treatment of PFCM (100 and 200 mg/kg, i.p) and dexamethasone (1 mg/kg, i.p) showed significantly altered the LPS-induced behavioural, anorexia and biochemical parameters. The bioactive compounds such as hesperidin, naringenine, naringin and dexamethasone showed docking score of -22.49, -21.99, -16.43 and -11.12 respectively against NF-κB (1NFK). Among tested bioactive compounds, naringin clearly exhibited higher inhibiting property on target protein structure. The protective effect of PFCM in LPS-induced anorexia and sickness behaviour is due to its antioxidant, anti-inflammatory and appetizing activities, inhibiting IL-6 and NF-κB.


Assuntos
Anorexia/metabolismo , Citrus , Comportamento de Doença/efeitos dos fármacos , Simulação de Acoplamento Molecular/métodos , NF-kappa B/metabolismo , Extratos Vegetais/uso terapêutico , Animais , Anorexia/induzido quimicamente , Anorexia/prevenção & controle , Biomarcadores/metabolismo , Relação Dose-Resposta a Droga , Comportamento de Doença/fisiologia , Lipopolissacarídeos/toxicidade , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Camundongos , NF-kappa B/antagonistas & inibidores , NF-kappa B/química , Fenóis/farmacologia , Fenóis/uso terapêutico , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Estrutura Terciária de Proteína , Distribuição Aleatória
18.
Biomedica ; 38(3): 437-450, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30335249

RESUMO

The serotonergic and immunological hypothesis of depression proposes that certain types of excessive stress distort the relationship between the activities of the innate immune and central nervous systems, so that the stress caused by an infection, or excessive psychological stress, activate toll-like receptors such as the TLR-4, the transcription factor NF-kB, the inflammasome NLRP3, as well as the secretion of interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and other factors of the innate immune response, causing first, the general symptoms of the disease which appear with any infection, but also those characteristic of depressive illness such as dysphoria and anhedonia. The evidence indicates that, if the stimulus persists or recurs within 24 hours, the indole-2, 3-dioxygenase enzyme (IDO) of the kynurenine metabolic pathway, which increases the synthesis of quinolinic acid, is activated with an associated reduction of serotonin synthesis. Quinolinic acid activates NMDA receptors in the central nervous system and stimulates the secretion of interleukins IL-6 and 1L-1ß, among others, promoting hyper-activity of the HPA axis and reinforcing a bias of the tryptophan metabolism to produce quinolinic acid, and interleukins by the innate immune system, further reducing the synthesis of serotonin and consolidating the depressive process. We discuss the evidence showing that this process can be initiated by either interleukin stimulated by an infection or some vaccines or excessive psychological stress that activates the HPA axis together with said innate immune response, causing a process of aseptic inflammation in the central nervous system.


Assuntos
Depressão/fisiopatologia , Sistema Hipotálamo-Hipofisário/fisiopatologia , Cinurenina/metabolismo , Modelos Neurológicos , Modelos Psicológicos , Sistema Hipófise-Suprarrenal/fisiopatologia , Serotonina/metabolismo , Animais , Infecções Bacterianas/imunologia , Infecções Bacterianas/fisiopatologia , Encéfalo/fisiopatologia , Citocinas/fisiologia , Depressão/imunologia , Humanos , Sistema Hipotálamo-Hipofisário/imunologia , Comportamento de Doença/fisiologia , Imunidade Inata , Indolamina-Pirrol 2,3,-Dioxigenase/fisiologia , Inflamação/imunologia , Inflamação/fisiopatologia , Interleucinas/fisiologia , Neuroglia/fisiologia , Sistema Nervoso Periférico/imunologia , Sistema Nervoso Periférico/fisiopatologia , Sistema Hipófise-Suprarrenal/imunologia , Ácido Quinolínico/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , Serotonina/deficiência , Isolamento Social , Estresse Psicológico/imunologia , Estresse Psicológico/fisiopatologia , Receptor 4 Toll-Like/fisiologia , Triptofano/metabolismo , Vacinas/efeitos adversos
19.
Physiol Behav ; 197: 42-50, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30248302

RESUMO

Immune activity influences reproduction, however, the extent to which mating experience may inversely alter immune pathways is poorly understood. A few studies in humans suggest that mating triggers a circulating immune and hypothalamic-pituitary-adrenal axis response. In male rats, mating experience enhances neuroplasticity and improves cognitive function and affective-like behavior, independent of the physical activity component. Yet, the extent to which mating experience may influence immune responses in the brain remain unexplored. Here, we hypothesized that recent mating experience in male rats increases neuroinflammatory signaling (via lipopolysaccharide [LPS] stimulation, i.p.) and associated sickness behaviors (i.e., food intake, weight loss) relative to sexually-naïve controls. Virgin male rats were exposed to a sexually non-receptive (control) or sexually-receptive female for 30 min for six consecutive days. Immediately following the last mating experience, rats were administered a saline or LPS injection and euthanized four hours later. Mating increased Tnfα responses to LPS in the brain, which positively correlated with LPS-induced weight loss. Mating also increased peripheral corticosterone among saline-treated rats, but this corticosterone response was attenuated in the most proficient copulators (e.g., shortest latencies). Thus, recent mating experience may be a unique modulator of select stimulated inflammatory signals that are relevant to adaptive neuroimmune responses and behavior.


Assuntos
Encéfalo/imunologia , Inflamação/imunologia , Comportamento Sexual Animal/fisiologia , Animais , Corticosterona/sangue , Regulação da Expressão Gênica , Comportamento de Doença/fisiologia , Lipopolissacarídeos , Masculino , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo , Perda de Peso/imunologia
20.
Sci Rep ; 8(1): 14255, 2018 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-30250285

RESUMO

Body odors change with health status and the odors of sick animals can induce avoidance behaviors in healthy conspecifics. Exposure to sickness odors might also alter the physiology of healthy conspecifics and modify the odors they produce. We hypothesized that exposure to odors of sick (but non-infectious) animals would alter the odors of healthy cagemates. To induce sickness, we injected mice with a bacterial endotoxin, lipopolysaccharide. We used behavioral odor discrimination assays and analytical chemistry techniques followed by predictive classification modeling to ask about differences in volatile odorants produced by two types of healthy mice: those cohoused with healthy conspecifics and those cohoused with sick conspecifics. Mice trained in Y-maze behavioral assays to discriminate between the odors of healthy versus sick mice also discriminated between the odors of healthy mice cohoused with sick conspecifics and odors of healthy mice cohoused with healthy conspecifics. Chemical analyses paired with statistical modeling revealed a parallel phenomenon. Urine volatiles of healthy mice cohoused with sick partners were more likely to be classified as those of sick rather than healthy mice based on discriminant model predictions. Sickness-related odors could have cascading effects on neuroendocrine or immune responses of healthy conspecifics, and could affect individual behaviors, social dynamics, and pathogen spread.


Assuntos
Aprendizagem da Esquiva/fisiologia , Comportamento Animal/fisiologia , Olfato/fisiologia , Comportamento Social , Animais , Comportamento de Doença/fisiologia , Masculino , Camundongos , Odorantes/análise
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