RESUMO
Food allergy accounts for a great number of reactions leading to diminished quality of life in western countries. There has been an abundance of reports of behavioral changes, as well as psychiatric conditions associated with food allergy over the past decades. Most of this field inspired little medical attention for its lack of a solid scientific ground. We review the literature on the association of food allergy and brain activity, leading to changes in emotion and behavior. Moreover, we describe an experimental paradigm employed to dissect the biological relevance of this association. Mice allergic to ovalbumin avoid a palatable sweet solution in order to escape contact with antigen. This choice is associated with increased levels of anxiety, compatible with a conflicting situation. These responses are associated with increased activity in brain areas associated with emotional and affective behavior, which are also important for anxiety and stress responses. Higher levels of corticosterone accompany these changes in behavior. These responses are mediated by specific antibodies and prevented by depletion or immunological tolerance. They are also partially mediated by C-sensitive afferents and mast cells. Far from anecdote, neural repercussions of food allergy should be considered when planning a therapeutic strategy in affected individuals.
Assuntos
Hipersensibilidade Alimentar/imunologia , Tonsila do Cerebelo/imunologia , Tonsila do Cerebelo/metabolismo , Animais , Anticorpos/imunologia , Anticorpos/metabolismo , Encéfalo/metabolismo , Hipersensibilidade Alimentar/metabolismo , Humanos , Hipotálamo/imunologia , Hipotálamo/metabolismo , Mastócitos/imunologia , Mastócitos/metabolismo , Fibras Nervosas/imunologia , Fibras Nervosas/metabolismo , Neuroimunomodulação , Transdução de SinaisRESUMO
Animals sensitized to allergens change their feeding behavior and avoid drinking the otherwise preferred sweetened solutions containing the allergens. This phenomenon, known as food aversion, appears to be mediated by allergen-specific IgE antibodies. Here we investigated food aversion in BALB/c and C57BL/6 mice, which differ in their allergic responses to the allergen ovalbumin as well as in their preference for sweet taste. BALB/c mice present higher levels of IgE and a natural lower preference for sweet flavors when compared to C57BL/6 mice. Specifically, we studied a conflicting situation in which animals simultaneously experienced the aversive contact with the allergen and the attractive sweet taste of increasing concentrations of sucrose. We found that BALB/c mice were more prone to develop food aversion than C57BL/6 mice and that this aversive behavior could be abolished in both strains by increasing the palatability of the solution containing the allergen. In both strains food aversion was positively correlated with the levels of allergen-specific IgE antibodies and inversely correlated with their preference for sucrose sweetened solutions.
Assuntos
Alérgenos/farmacologia , Comportamento Alimentar/fisiologia , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/psicologia , Preferências Alimentares/fisiologia , Imunoglobulina E/imunologia , Paladar/fisiologia , Alérgenos/imunologia , Aminoácidos/farmacologia , Animais , Soros Imunes/farmacologia , Imunização Passiva , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Ovalbumina/imunologia , Especificidade da Espécie , Edulcorantes/farmacologiaRESUMO
Neuroimmunomodulation describes the field focused on understanding the mechanisms by which the central nervous system interacts with the immune system, potentially leading to changes in animal behavior. Nonetheless, not many articles dealing with neuroimmunomodulation employ behavior as an analytical endpoint. Even fewer papers deal with social status as a possible modifier of neuroimmune phenomena. In the described sets of experiments, we tackle both, using a paradigm of social dominance and subordination. We first review data on the effects of different ranks within a stable hierarchical relationship. Submissive mice in this condition display more anxiety-like behaviors, have decreased innate immunity, and show a decreased resistance to implantation and development of melanoma metastases in their lungs. This suggests that even in a stable, social, hierarchical rank, submissive animals may be subjected to higher levels of stress, with putative biological relevance to host susceptibility to disease. Second, we review data on how dominant and submissive mice respond differentially to lipopolysaccharide (LPS), employing a motivational perspective to sickness behavior. Dominant animals display decreased number and frequency in several aspects of behavior, particularly agonistic social interaction, that is, directed toward the submissive cage mate. This was not observed in submissive mice that maintained the required behavior expected by its dominant mate. Expression of sickness behavior relies on motivational reorganization of priorities, which are different along different social ranks, leading to diverse outcomes. We suggest that in vitro assessment of neuroimmune phenomena can only be understood based on the behavioral context in which they occur.
Assuntos
Comportamento/fisiologia , Encéfalo/fisiologia , Sistema Imunitário/fisiologia , Animais , Hierarquia Social , Humanos , Comportamento de Doença , Imunidade InataRESUMO
Acute infections lead to alterations in behavior, collectively known as sickness behavior, which includes reduction in locomotion, food ingestion, sexual and social behavior, environmental exploration, and sleep profile. Although generally seen as undesired, sickness behavior represents a conserved strategy for animals to overcome disease. Aging process is associated with a variety of changes in immunity, which are referred to as immunosenescence, and include higher mortality by infectious diseases. Few works studied sickness behavior display in old animals. Thus, we sought to investigate the display of sickness related behaviors on aged mice. Adult (3-6 months old), middle-aged (12-15 m) and aged mice (18-22 m) were treated with i.p. LPS (200 microg/kg) and their behaviors were assessed in the open field and in the elevated plus-maze. Exploratory activity was similar in aged mice treated or not with LPS in both apparati. In the open field, locomotion remained at baseline levels; in the elevated plus-maze, there was a time-dependent decrease in motor activity.
Assuntos
Envelhecimento/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Envelhecimento/fisiologia , Análise de Variância , Animais , Peso Corporal/efeitos dos fármacos , Comportamento Exploratório/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C3HRESUMO
Pfaffia paniculata (Brazilian ginseng) roots have been indicated for the treatment of several diseases. Our studies have shown that P. paniculata roots present antineoplastic effects and cancer chemopreventive activity in a mouse hepatocarcinogenesis model. The purpose of this study was to investigate the effects of the Brazilian ginseng on corneal angiogenesis in mice. We first conducted a toxicological study employing 250, 500, or 1000mg/kg/day of the methanolic extract of P. paniculata roots by gavage to BALB/c mice. Animals did not lose weight during the treatment nor presented histopathological alterations. The effect of this root on angiogenesis in the cornea of BALB/c mice was then assessed. Male mice were treated, by gavage, once a day, with doses of 250, 500, or 1000mg/kg of methanolic extract of P. paniculata powdered root for 10 days; filtered water was used as control. Corneal cauterization was accomplished by the contact of a silver nitrate crystal on the central area of the cornea, in the 5th day of treatment with P. paniculata, which continued thereafter; the animals were euthanized on the 6th day after cauterization. Newly formed blood vessels were filled with India ink, and the corneas were routinely processed. Blood vessels were quantified in an image analysis system. A smaller total area of neovascularization in the mouse cornea was observed in animals treated with 1000mg/kg of the methanolic extract of P. paniculata. These results indicate an antiangiogenic effect of this extract. The mechanisms of this antiangiogenic activity of P. paniculata should be further investigated.
Assuntos
Amaranthaceae/química , Inibidores da Angiogênese/uso terapêutico , Córnea/irrigação sanguínea , Neovascularização da Córnea/tratamento farmacológico , Panax , Extratos Vegetais/uso terapêutico , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Cauterização/efeitos adversos , Neovascularização da Córnea/patologia , Relação Dose-Resposta a Droga , Masculino , Metanol/química , Camundongos , Camundongos Endogâmicos BALB C , Raízes de Plantas/química , Testes de ToxicidadeRESUMO
Granuloma formation involves a coordinated interaction between monocytes and macrophages, epithelioid cells, lymphocytes, eosinophils, neutrophils and fibroblasts. It has been established that extracellular communication via cytokines is important for the assembly of granulomas. However, the importance of gap junctions and intercellular communication to granuloma formation and development had never been assessed. Connexins are proteins that form gap junctions, and connexin 43 (Cx43) is present in macrophages, lymphoid cells, myelogenous cells, fibroblasts and others. We analyzed the effect of heterologous deletion of Gja1 (Cx43 gene) on the formation and development of hepatic granulomas induced by Schistosoma mansoni eggs. Heterozygous (Cx43(+/-)) and wild-type (Cx43(+/+)) mice were infected subcutaneously with S. mansoni cercarie and evaluated after 6, 8 and 12 weeks. Granuloma cells express Cx43, as revealed by real-time PCR in isolated granulomas, and by immunohistochemistry. Cx43 expression was reduced in Cx43(+/-) mice, as expected. No differences in the average area of granulomas or number of cells per granuloma were observed between mice of different genotypes. However, granuloma cells from Cx43(+/-) mice displayed a reduced index of the proliferating cell nuclear antigen (PCNA) labeling at 8 and 12 weeks post-infection. Moreover, Cx43(+/-) granulomas unexpectedly presented a higher degree of fibrosis, quantified by morphometric analysis in Sirius Red-stained slides. Our results indicate that the deletion of one allele of the Cx43 gene, and possibly the reduced gap junction intercellular communication capacity (GJIC), may impair the interactions between granuloma cells, reducing their proliferation and increasing their collagen content, thereby modifying the characteristics of S. mansoni granuloma in mice.
Assuntos
Colágeno/metabolismo , Conexina 43/deficiência , Granuloma/patologia , Hepatopatias/patologia , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/patologia , Animais , Contagem de Células , Proliferação de Células , Modelos Animais de Doenças , Técnica Indireta de Fluorescência para Anticorpo , Inativação Gênica , Granuloma/metabolismo , Granuloma/parasitologia , Hepatopatias/metabolismo , Hepatopatias/parasitologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Antígeno Nuclear de Célula em Proliferação/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Esquistossomose mansoni/metabolismoRESUMO
Experimental airway allergy in mice leads to increased activity in specific hypothalamic and amygdaloid nuclei, and behavioral changes. The experiments described here were designed to determine the role of anaphylactic antibodies, mast cell degranulation, and lung inflammation in the neural and behavioral correlates of an experimental murine asthma-like response. Animals were sensitized intraperitoneally with ovalbumin adsorbed to alum, and challenged by intranasal ovalbumin instillation or aerosol. To induce immunological tolerance, animals were fed ovalbumin in the drinking water for 5 consecutive days, along with primary sensitization. Depletion of IgE was also accomplished with a non-anaphylactic anti-IgE antibody. Mast cell degranulation was inhibited by cromolyn. In addition to BALB/c animals, C3H/HeJ mice were used for their relative resistance to lung allergic inflammation. We confirmed that ovalbumin challenge in allergic mice leads to increased activity in the paraventricular nucleus of the hypothalamus and central nucleus of the amygdala, and avoidance behavior towards an allergen-associated compartment. Moreover, these responses were precluded by oral tolerance or anti-IgE treatment, even in the presence of IgG1. Cromolyn abrogates both responses in the presence of anaphylactic antibodies. Finally, although sensitized C3H/HeJ mice did not develop airway inflammation, they exhibited brain and behavioral changes similar to BALB/c animals. The repercussions of murine allergic asthma on brain and behavior are IgE-dependent, mediated by mast cell degranulation, and do not require a pulmonary inflammatory infiltrate, suggesting that the early phase of this immediate allergic response suffices for the brain activation associated with avoidance behavior towards exposure to the allergen.
Assuntos
Tonsila do Cerebelo/fisiologia , Asma/imunologia , Comportamento Animal/fisiologia , Degranulação Celular/imunologia , Hipersensibilidade/imunologia , Mastócitos/fisiologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Tonsila do Cerebelo/imunologia , Análise de Variância , Anafilaxia/imunologia , Animais , Aprendizagem da Esquiva/fisiologia , Modelos Animais de Doenças , Tolerância Imunológica/imunologia , Imunoglobulina E/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Neuroimunomodulação/imunologia , Neuroimunomodulação/fisiologia , Ovalbumina/imunologia , Núcleo Hipotalâmico Paraventricular/imunologia , Especificidade da Espécie , Estatísticas não ParamétricasRESUMO
Although many authors have considered a direct interaction between allergic reactions and behavioral changes, supporting evidence has been elusive. In this series of studies we show that after oral or nasal ovalbumin (OVA) challenge, allergic mice present increased Fos expression in the paraventricular nucleus of the hypothalamus (PVN) and in the central nucleus of the amygdala (CeA). Mice with food allergy display higher levels of anxiety and increased serum corticosterone levels, and allergy-activated neurons express corticotropin-releasing factor (CRF) in the PVN and CeA. OVA-allergic mice develop aversion to an antigen-containing solution, and also avoid a dark compartment previously associated with nebulized OVA. Results on brain Fos expression and behavioral data seem compatible with adaptive responses. Removal of IgE by either antibody depletion or the development of oral tolerance precluded all responses analyzed here. C-sensitive fiber destruction by neonatal capsaicin inhibited the activation in the PVN, but not in the CeA, and decreased the magnitude of food aversion. Cromolyn, a mast cell stabilizer, completely blocked Fos expression in the PVN and CeA, and precluded the development of aversion to the dark compartment associated with nebulized OVA. Employing mice that do not develop an important inflammatory infiltrate following nasal OVA challenge, we found that inflammatory cells are not required at the site of challenge in order to trigger neural or behavioral correlates of murine experimental asthma. Altogether, we have built a solid foundation for understanding neuroimmune interactions during allergic responses that may contribute to the comprehension of psychological disorders associated with allergy.
Assuntos
Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Neuroimunomodulação/imunologia , Animais , Asma/imunologia , HumanosRESUMO
Notothenia coriiceps (Cabeçuda) is an Antarctic benthic fish frequently found with lesions in the tegument caused by seal predation. We have investigated epidermal repair in these animals by means of a microscopic study of experimental wound healing at 0 degrees C. At 24--48 h after wound induction, mucous exudate and necrotic lining cells covered the wound. At 7--14 days, an epidermal "tongue" could be discerned, folded at the tip, with intercellular oedema between the tip and the wound border. After 23--30 days, the wound was completely closed and the migrating epidermis, with intercellular oedema, was reduced. By 45--90 days, melanocytes progressively increased in the epidermis but no scales were formed. The inflammatory infiltrate was mainly composed of neutrophils after 7 days, at which time they were mostly replaced by macrophages; lymphocytes and plasma cells were also present. The border epidermis slid towards the centre, folding at the tip and finally fusing to form a diaphragm. The cells of the epidermis began to multiply only after complete closure of the wound. The lack of scale formation on induced and naturally found wounds, even after 90 days, suggests that different mechanisms in wound repair occur at 0 degrees C from those in fish from temperate and tropical environment. This is the first report of successful wound repair at polar temperatures, indicating the adaptation of N. coriiceps to the Antarctic environment.
Assuntos
Epiderme , Peixes , Cicatrização , Animais , Regiões Antárticas , Movimento Celular , Epiderme/metabolismo , Epiderme/patologia , Epiderme/ultraestrutura , Peixes/anatomia & histologia , Peixes/fisiologia , Inflamação/patologia , Fatores de TempoRESUMO
Allergic asthma is characterized by intermittent airway obstruction, inflammation, airway hyperreactivity, and increased production of IgE. The pathophysiology of asthma is well understood but little is known about its influences on brain activity and behavior. We recently described the neural correlates of food allergy and its associated modulation of behavior using an experimental model that also generates a T helper type 2 (Th2)-skewed response, with high levels of IgE. Here we show that mice allergic to ovalbumin (OVA) have an increase in the activity of the paraventricular nucleus of the hypothalamus (PVN) and in the central nucleus of the amygdala (CeA) following a single nasal OVA challenge. Moreover, we adapted a classical passive avoidance test using an OVA aerosol as the aversive stimulus. We found that allergic mice avoid entering the dark compartment of the apparatus that had been previously associated with nebulization of the allergen, while their non-immunized controls still move into the dark side of the test box. Thus, allergic mice have increased activity in areas of the CNS commonly associated with emotionality-related behavioral responses, such as the avoidance of a context previously associated with an unpleasant or harmful situation. Moreover, our findings on the avoidance test illustrate that previous experience with an airborne allergen can modify behavior.