RESUMO
BACKGROUND: In captive colonies, owl monkeys' mothers sometimes reject their newborns. To prevent, mortality infants are manually raised by veterinarians. Both parental separation and rejection are stressful experiences, associated with elevated stress, physical, and behavioural disorders. The effect of parental deprivation in IVITA's owl monkeys stress profiles and health is unknown. METHODS: We compared stress biomarkers such as hair cortisol (using cortisol ELISA), stereotypic behaviours (with infrared cameras), and infection histories in juveniles separated from parents soon after birth (n = 14, ~17 months) and controls (n = 11, ~17 months). RESULTS: Parentally deprived owl monkeys show higher infection rates than controls (p = .001). However, they display no higher incidence of biomarkers of stress: Neither stereotypic behaviour nor cortisol in hair was different between cohorts. Irrespective of deprivation status, rates of infection, and concentration of cortisol in hair were positively associated (R2 = .29, p = .005). CONCLUSION: Early parental deprivation and natural high levels of cortisol secretion are associated with elevated infection levels in the IVITA owl monkey juveniles detectable up to 17 months post separation.
Assuntos
Aotidae , Hidrocortisona , Animais , Biomarcadores , CabeloRESUMO
The blood-brain barrier (BBB), a critical guardian of communication between the periphery and the brain, is frequently compromised in neurological diseases such as multiple sclerosis (MS), resulting in the inappropriate passage of molecules and leukocytes into the brain. Here we show that the glucocorticoid anti-inflammatory messenger annexin A1 (ANXA1) is expressed in brain microvascular endothelial cells, where it regulates BBB integrity. In particular, ANXA1(-/-) mice exhibit significantly increased BBB permeability as a result of disrupted interendothelial cell tight junctions, essentially related to changes in the actin cytoskeleton, which stabilizes tight and adherens junctions. This situation is reminiscent of early MS pathology, a relationship confirmed by our detection of a selective loss of ANXA1 in the plasma and cerebrovascular endothelium of patients with MS. Importantly, this loss is swiftly restored by i.v. administration of human recombinant ANXA1. Analysis in vitro confirms that treatment of cerebrovascular endothelial cells with recombinant ANXA1 restores cell polarity, cytoskeleton integrity, and paracellular permeability through inhibition of the small G protein RhoA. We thus propose ANXA1 as a critical physiological regulator of BBB integrity and suggest it may have utility in the treatment of MS, correcting BBB function and hence ameliorating disease.
Assuntos
Anexina A1/fisiologia , Barreira Hematoencefálica/fisiologia , Citoesqueleto de Actina/fisiologia , Junções Aderentes/patologia , Junções Aderentes/fisiologia , Adulto , Idoso , Animais , Anexina A1/antagonistas & inibidores , Anexina A1/deficiência , Anexina A1/genética , Anexina A1/farmacologia , Barreira Hematoencefálica/patologia , Barreira Hematoencefálica/fisiopatologia , Permeabilidade Capilar/fisiologia , Linhagem Celular , Células Endoteliais/patologia , Células Endoteliais/fisiologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microvasos/patologia , Microvasos/fisiopatologia , Pessoa de Meia-Idade , Modelos Neurológicos , Esclerose Múltipla/patologia , Esclerose Múltipla/fisiopatologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Proteínas de Junções Íntimas/fisiologia , Proteína rhoA de Ligação ao GTP/metabolismoRESUMO
Repetitive overload is a primary factor in tendon injury, causing progressive accumulation of matrix damage concurrent with a cellular response. However, it remains unclear how these events occur at the initial stages of the disease, making it difficult to identify appropriate treatment approaches. Here, we describe the development of a new model to cyclically load the Achilles tendon (AT) of rats in vivo and investigate the initial structural and cellular responses. The model utilizes controlled dorsiflexion of the ankle joint applied near maximal dorsiflexion, for 10,000 cycles at 3 Hz. Animals were subjected to a single bout of in vivo loading under anaesthesia, and either culled immediately (without recovery from anaesthesia), or 48 h or 4-weeks post-loading. Macro strains were assessed in cadavers, whilst tendon specific microdamage was assessed through collagen-hybridizing peptide (CHP) immunohistochemistry which highlighted a significant rise in CHP staining in loaded ATs compared to contralateral controls, indicating an accumulation of overload-induced damage. Staining for pro-inflammatory mediators (IL-6 and COX-2) and matrix degradation markers (MMP-3 and -13) also suggests an initial cellular response to overload. Model validation confirmed our approach was able to explore early overload-induced damage within the AT, with microdamage present and no evidence of broader musculoskeletal damage. The new model may be implemented to map the progression of tendinopathy in the AT, and thus study potential therapeutic interventions.
Assuntos
Tendão do Calcâneo , Tendinopatia , Traumatismos dos Tendões , Ratos , Animais , Tendão do Calcâneo/lesões , Traumatismos dos Tendões/complicações , Colágeno/metabolismo , Articulação do TornozeloRESUMO
RATIONALE: Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are increasingly used for the treatment of depression in children. Limited data are, however, available on their effects on brain development and their efficacy remains debated. Moreover, previous experimental studies are seriously hampered in their clinical relevance. OBJECTIVES: The aim of the present study was to investigate putative age-related effects of a chronic treatment with fluoxetine (5 mg/kg, either orally or i.p. for 3 weeks, 1 week washout) using conventional methods (behavioral testing and binding assay using [(123)I]ß-CIT) and a novel magnetic resonance imaging (MRI) approach. METHODS: Behavior was assessed, as well as serotonin transporter (SERT) availability and function through ex vivo binding assays and in vivo pharmacological MRI (phMRI) with an acute fluoxetine challenge (10 mg/kg oral or 5 mg/kg i.v.) in adolescent and adult rats. RESULTS: Fluoxetine caused an increase in anxiety-like behavior in treated adult, but not adolescent, rats. On the binding assays, we observed increased SERT densities in most cortical brain regions and hypothalamus in adolescent, but not adult, treated rats. Finally, reductions in brain activation were observed with phMRI following treatment, in both adult and adolescent treated animals. CONCLUSION: Collectively, our data indicate that the short-term effects of fluoxetine on the 5-HT system may be age-dependent. These findings could reflect structural and functional rearrangements in the developing brain that do not occur in the matured rat brain. phMRI possibly will be well suited to study this important issue in the pediatric population.