Stress as cause of signs and symptoms of pseudo-Cushing's syndrome in buffy-tufted marmosets (Callithrix aurita).

Hyperadrenocorticism is a medical condition caused by the increase in cortisol production by the cortex of the adrenal gland. Although infrequently described in most animal species, its naturally occurring form, called Cushing's syndrome, is the most prevalent endocrinopathy in dogs. Cushing's syndrome is also present in humans and might be confused with the pseudo-Cushing's syndrome (PCS), rarely described in animals. PCS shares many of the clinical and biochemical features of Cushing's syndrome. However, the hypercortisolemia seen is usually idiopathic and, in some circumstances, associated with psychological disruptions. This report describes PCS-like disorder in two marmosets Callithrix aurita that were exposed to environmental changes, suggesting stress as the main cause of the process and reviewing the mechanisms involved in the pathogeny of the two syndromes.

GCN2 kinase plays an important role triggering the remission phase of experimental autoimmune encephalomyelitis (EAE) in mice.

Experimental autoimmune encephalomyelitis (EAE) has been widely employed as a model to study multiple sclerosis (MS) and indeed has allowed some important advances in our comprehension of MS pathogenesis. Several pieces of evidence suggest that infiltrating Th1 and Th17 lymphocytes are important players leading to CNS demyelination and lesion during the peak of murine EAE. Subsequently, effector T cell responses rapidly decline and the recovery phase of the disease strongly correlates with the expression of anti-inflammatory cytokines and the enrichment of Foxp3+ regulatory T (Treg) cells within the target organ. However, the mechanisms leading to the increased presence of Treg cells and to the remission phase of the disease are still poorly understood. Recent researches demonstrated that chemically induced amino-acid starvation response might suppress CNS immune activity. Here we verified an important participation of the general control nonrepressible 2 (GCN2), a key regulator kinase of the amino-acid starvation response, in the development of the remission phase of EAE in C57BL/6 mice. By immunizing wild type C57BL/6 (WT) and GCN2 knock-out mice (GCN2 KO) with myelin oligodendrocyte glycoprotein peptide (MOG35-55), it was noticed that GCN2 KO mice did not develop the remission phase of the disease and this was associated with higher levels of CNS inflammation and increased presence of effector T cells (Th1/Th17). These animals also showed lower frequency of Treg cells within the CNS as compared to WT animals. Higher expression of indoleamine 2,3-dioxygenase (IDO) and higher frequency of plasmacytoid dendritic cells (pDCs) were found at the peak of the disease in the CNS of WT animals. Our results suggest that the GCN2 kinase-dependent sensing of IDO activity represents an important trigger to the EAE remission phase. The IDO-mediated immunoregulatory events may include the arresting of effector T cell responses and the differentiation/expansion of Treg cells within the target organ.

Participação astrocitária na desmielinização do sistema nervoso central (SNC) de cães com cinomose - revisão da literatura / Astrocytic participation in the demyelinating process of the central nervous system (CNS) in canine distemper - a review

A cinomose é uma importante doença viral que acomete cães e outros carnívoros de forma multissistêmica. No sistema nervoso central (SNC), gera lesões desmielinizantes severas, cuja patogenia é ainda pouco esclarecida. Na tentativa de elucidar os eventos celulares envolvidos nos processos de perda e de reparo mielínico, diversos tipos celulares têm sido estudados e os astrócitos parecem desempenhar importantes funções na sua mediação. Este trabalho visa descrever o processo de desmielinização do SNC na cinomose e os eventos celulares nele envolvidos, enfatizando os astrócitos como possíveis indutores do processo de desmielinização.

The canine distemper is an important viral disease that affects dogs and other carnivores in a multissistemic form. In the central nervous system (CNS), it develops severe demyelinating lesions which pathogenesis is poorly explained. Intending to elucidate the cellular events involved in the process of myelin loss and repair, different cells have been studied and astrocytes seem to develop important mediating functions. This study aims to describe the CNS demyelinating process in canine distemper and the cellular events involved in it, emphasizing astrocytes as possible inducers of the demyelinating process.

[Immunohistochemical staining of the astrocytic expression of glial fibrillary acidic protein and vimentin in the central nervous system of dogs with canine distemper]. / Marcação imunoistoquímica da expressão astrocitária de proteína glial fibrilar ácida e de vimentina no sistema nervoso central de cães com cinomose.

Considering that many aspects involved in the pathogenesis of the central nervous system (CNS) demyelinating diseases are still poorly understood and that astrocytes seem to mediate such processes, this study analyzed the participation of astrocytes in the demyelinating processes of CNS by using immunohistochemical staining of two astrocytic proteins--glial fibrillary acidic protein (GFAP) and vimentin (VIM)--comparing samples of cerebellum and brainstem from eight dogs with canine distemper and from two healthy dogs, from different breeds and ages varying from 1 to 4 years old. Histological sections were submitted to the avidin-biotin-peroxidase indirect method of immunohistochemical staining (ABC) and the astrocytic reactivity, observed in light microscopy, was quantified in a computer system for image analysis. It was possible to notice, on most of the sections from sick animals, degenerative lesions that indicate demyelination. The immunostaining for GFAP and VIM was more intense on animals with canine distemper, specially around the ventricules and near degenerated sites. There was no significant difference between the immunostaining (GFAP and VIM) of animals with canine distemper with and without inflammatory infiltrate of the cerebellar white matter. The increased immunoreactivity of astrocytes for GFAP and the VIM reexpression in injured areas indicate the astrocytic involvement on nervous tissue response to the demyelinating lesions induced by the canine distemper virus (CDV) in the CNS.

Marcação imunoistoquímica da expressão astrocitária de proteína glial fibrilar ácida e de vimentina no sistema nervoso central de cães com cinomose / Immunohistochemical staining of the astrocytic expression of glial fibrillary acidic protein and vimentin in the central nervous system of dogs with canine distemper

Uma vez que muitos dos aspectos envolvidos na patogenia dos processos desmielinizantes do sistema nervoso central (SNC) são ainda pouco esclarecidos e que os astrócitos parecem estar envolvidos na mediação de tais processos, este estudo analisou morfologicamente a participação astrocitária na desmielinização do SNC por meio da marcação imunoistoquímica de duas proteínas dos filamentos intermediários astrocitários - a proteína glial fibrilar ácida (GFAP) e a vimentina (VIM) -, comparando amostras de cerebelo e de tronco encefálico de oito cães com cinomose e de dois cães normais, de diferentes raças e com idades entre um e quatro anos. Cortes histológicos dos tecidos foram submetidos à marcação pelo método indireto da avidina-biotina-peroxidase (ABC) e a reatividade astrocitária, observada em microscopia de luz, foi quantificada em um sistema computacional de análise de imagens. Observou-se, na maioria dos cortes de animais doentes, a presença de lesões degenerativas compatíveis com desmielinização. A marcação para a GFAP e para a VIM foi mais intensa nos animais com cinomose do que nos animais normais, especialmente nas regiões circunventriculares e nas adjacentes às áreas de degeneração tecidual. Não houve diferença significativa entre a imunomarcação (GFAP e VIM) dos animais com cinomose com e sem infiltração inflamatória da substância branca do cerebelo. O aumento da imunorreatividade dos astrócitos para a GFAP e a reexpressão de VIM nas áreas lesionais indicam o envolvimento astrocitário na resposta do tecido nervoso às lesões desmielinizantes induzidas pelo vírus da cinomose (CDV) no SNC.

Considering that many aspects involved in the pathogenesis of the central nervous system (CNS) demyelinating diseases are still poorly understood and that astrocytes seem to mediate such processes, this study analyzed the participation of astrocytes in the demyelinating processes of CNS by using immunohistochemical staining of two astrocytic proteins - glial fibrillary acidic protein (GFAP) and vimentin (VIM) -, comparing samples of cerebellum and brainstem from eight dogs with canine distemper and from two healthy dogs, from different breeds and ages varying from 1 to 4 years old. Histological sections were submitted to the avidin-biotin-peroxidase indirect method of immmunohistochemical staining (ABC) and the astrocytic reactivity, observed in light microscopy, was quantified in a computer system for image analysis. It was possible to notice, on most of the sections from sick animals, degenerative lesions that indicate demyelination. The immunostaining for GFAP and VIM was more intense on animals with canine distemper, specially around the ventricules and near degenerated sites. There was no significant difference between the immunostaining (GFAP and VIM) of animals with canine distemper with and without inflammatory infiltrate of the cerebellar white matter. The increased immunoreactivity of astrocytes for GFAP and the VIM reexpression in injured areas indicate the astrocytic involvement on nervous tissue response to the demyelinating lesions induced by the canine distemper virus (CDV) in the CNS.

[Evaluation of locomotor activity after a local induction of toxic demyelination in the brainstem of Wistar rats]. / Avaliação da atividade locomotora após indução local de desmielinização tóxica no tronco encefálico de ratos Wistar.

Ethidium-bromide (EB)-induced lesions have been used to investigate the incomplete remyelination in the central nervous system, as well as to evaluate therapeutic strategies to accelerate the reconstruction of the lost myelin sheaths. Although many electrophysiologic studies were performed in situations of experimental demyelination and remyelination, their behavioural effects have not been properly analyzed. In this study, we investigated ultrastructurally the EB - demyelinating lesions as well as the locomotor activity of rats during the beam walking test after a focal induction of demyelination using the EB model in the ventral surface of the brainstem. It was observed the occurrence of locomotor deficits until 31 days post-injection, as well as that subsequent remyelination was related to the return of the lost function.

Avaliação da atividade locomotora após indução local de desmielinização tóxica no tronco encefálico de ratos Wistar / Evaluation of locomotor activity after a local induction of toxic demyelination in the brainstem of Wistar rats

Lesões desmielinizantes induzidas pelo gliotóxico brometo de etídio (BE) têm sido estudadas com o objetivo de permitir a compreensão do limitado processo de reparo mielínico no sistema nervoso central, bem como avaliar estratégias terapêuticas no sentido de acelerar a reconstrução das bainhas de mielina perdidas. Muito embora estudos eletrofisiológicos correlacionando situações de desmielinização e remielinização experimental sejam bem estabelecidos, os efeitos comportamentais não têm sido adequadamente investigados. Neste estudo, foram analisadas ultra-estruturalmente as lesões desmielinizantes e a atividade locomotora de ratos submetidos à indução focal de desmielinização pelo modelo do BE na superfície ventral do tronco encefálico, mediante observação de sua movimentação e controle motor durante a travessia de uma trave elevada de madeira (beam walking test). Foi observada a ocorrência de deficiências locomotoras até 31 dias pós-injeção de BE, constatando-se ainda que a subseqüente remielinização estava relacionada com o retorno da função perdida.

Fisiopatologia do estresse em animais selvagens em cativeiro e suas implicações no comportamento e bem-estar animal: revisão da literatura / Physiopathology of stress in captive wild animals and its implications on animal behaviour and well-being: a review

Estimativas atuais sugerem que a população animal está diminuindo na natureza, principalmente pela ação humana na destruição de hábitats. Desta forma, a criação de animais selvagens em cativeiro vem ganhando importância na conservação de espécies. No entanto, a manutenção desses animais em um ambiente artificial e não estimulante pode trazer sérios problemas para sua saúde e comportamento, problemas estes normalmente relacionados a condições estressantes do cativeiro. Portanto, uma vez que o cativeiro se torne, algumas vezes, necessário para a conservação da vida selvagem, deve-se ter uma preocupação com o bem-estar animal, utilizando-se para isso técnicas para estimular o interesse do animal pelo ambiente em que se encontra e reduzir o seu padecimento. Este trabalho descreve os eventos relacionados ao estresse,com o objetivo de apresentar as suas possíveis implicações na saúde e no bem-estar animal, enfatizando a importância da observação do comportamento como um indicador do estresse e sugerindo alguns métodos para reduzir o sofrimento animal durante o período decativeiro.

Current estimates suggest that the animal population is decreasing in nature, especially due to human actions in habitat destruction. From this point of view, the captive breeding of wild animals is becoming important to conserve species. However, the maintenance of these animals in an artificial, non-stimulant environment can cause serious health and behaviour problems, usually related to these stressful conditions. Therefore, since captivity is sometimes necessary towild-life conservation, there must be a concern about animals' well-being, by using some techniques that stimulate the interest of the animals to their environment and reduce their suffering. This paper describes the events related to stress, specially their implications in animal health and well-being, emphasizing how important it is to observe the animal behaviour as an indicator of stress and suggesting some methods to reduce animal suffering during confinement periods.