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1.
Brain Behav Immun ; 80: 56-65, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30797960

RESUMO

Fetal exposure to intrauterine inflammation (IUI) affects brain development. Using intrauterine lipopolysaccharide (LPS) administration to induce a localized, rather than a systemic, inflammation, we have previously shown that IUI increases cytokine expression and microglia number, and reduces white matter in the brains of exposed offspring. Clinical data suggest that IUI may increase the risk for cognitive and neurodevelopmental disorders, however, IUI is often found in the context of preterm birth, making it difficult to disentangle the adverse effects of inflammation from those related to prematurity. Therefore, using a mouse model of IUI that does not involve preterm birth, operant tasks were used to evaluate motivation, attention, impulsivity, and locomotion. IUI-exposed offspring were found to have increased locomotion and increased motivation (females only), and testing in the 5-choice serial reaction time task (5-CSRTT) showed that IUI-exposed offspring performed more trials and could respond accurately at a shorter stimulus length. We have previously shown that IUI animals have a potentiated cytokine response to a "second hit" (acute LPS injection) in adulthood, so animals' performance in the 5CSRTT was evaluated following an acute injection of LPS. As opposed to the improved performance observed under baseline conditions, IUI exposed animals demonstrated a greater decrease in performance after an acute LPS administration. To identify putative molecular mechanisms underlying this potentiated decline in cognitive performance, PFC samples were collected immediately after post-LPS cognitive testing and targeted gene expression analysis was correlated with specific measures of cognitive performance. Three receptors important for neuron-microglia crosstalk were found to correlate with task performance in the males following acute LPS administration. These data demonstrate that early life exposure to localized inflammation of the uterus, in the absence of prematurity, increases locomotor activity and improves some aspects of cognitive performance, but drives a vulnerability for adult cognitive performance deficits in response to acute infection.


Assuntos
Disfunção Cognitiva/metabolismo , Inflamação/metabolismo , Locomoção/imunologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Animais , Encéfalo/metabolismo , Cognição/fisiologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Imunidade Ativa/imunologia , Inflamação/imunologia , Lipopolissacarídeos/farmacologia , Locomoção/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Microglia/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Fatores Sexuais , Útero/imunologia , Substância Branca/metabolismo
2.
Brain Behav Immun ; 73: 596-602, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29981831

RESUMO

In a previous study we showed a clear relationship between immune system and behavior in zebrafish and we hypothesized that the immune system is capable of inducing behavioral changes. To further investigate this subject and to address our main question, here we induced an inflammatory response in one group of fish by the inoculation of formalin-inactivated Aeromonoas hydrophila bacterin and compared their social and exploratory behavior with control groups. After the behavioral tests, we also analyzed the expression of cytokines genes and markers of neuronal activity in fish brain. In the bacterin-inoculated fish, the locomotor activity, social preference and exploratory behavior towards a new object were reduced compared to the control fish while the expression of proinflammatory cytokines in the brain was upregulated. With this study we demonstrated for the first time that the immune system is capable of causing behavioral changes that are consistent with the sickness behavior observed in mammals.


Assuntos
Comportamento de Doença/fisiologia , Peixe-Zebra/imunologia , Peixe-Zebra/fisiologia , Animais , Comportamento Animal/fisiologia , Encéfalo/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Comportamento Exploratório/fisiologia , Feminino , Sistema Imunitário/metabolismo , Relações Interpessoais , Locomoção/imunologia , Locomoção/fisiologia , Masculino , Atividade Motora/fisiologia , Neurônios/metabolismo
3.
Neuroimmunomodulation ; 25(1): 49-58, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29920498

RESUMO

OBJECTIVES: Ginsenoside Rg1 and mebicar have been reported to have broad efficacy spectrum, including anti-anxiety and anti-stress. These drugs have been used not only for treatment but also for the purpose of increasing resistance from disease. A specific aim of this study was to investigate whether mebicar or ginsenoside Rg1 can prevent physiological changes resulting from intermittent unpredictable stress (IUS). METHODS: Seven week-old Balb/cByJ mice were administered orally with mebicar (10 mg/kg) or ginsenoside Rg1 (10 mg/kg) starting from a week before they were exposed to IUS until the end of the experiment. IUS, which consists of psychological stress and physical fatigue, was set as 3 bouts (24 h/bout) exposure in a 2-week period. RESULTS: IUS caused hyperactivity and anxiety-like behavior, which were not inhibited by mebicar or ginsenoside Rg1. IUS mice treated with mebicar or ginsenoside Rg1 recovered rapidly from anxiety-like behavior induced by the multiplexed stress compared to the mice not orally treated with mebicar or ginsenoside Rg1. Mebicar or ginsenoside Rg1 could not prevent the decrease of brain-derived neurotropic factor by IUS exposure. However, mebicar or ginsenoside Rg1 prevented elevation of serum corticosterone and secretion of proinflammatory cytokines from splenocytes due to IUS exposure. CONCLUSIONS: This study suggests that mebicar or ginsenoside Rg1 may have little preventive effect on neurobehavioral disruption by IUS exposure, but mebicar or ginsenoside Rg1 shortened the lasting duration of the anxiety caused by exposure to a novel environment. The anti-stress effect of mebicar and ginsenoside Rg1 may be restricted in peripheral stress responses.


Assuntos
Ansiolíticos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Biureias/uso terapêutico , Ginsenosídeos/uso terapêutico , Locomoção/efeitos dos fármacos , Estresse Psicológico/tratamento farmacológico , Animais , Ansiolíticos/farmacologia , Transtornos de Ansiedade/imunologia , Transtornos de Ansiedade/psicologia , Biureias/farmacologia , Células Cultivadas , Fármacos do Sistema Nervoso Central/farmacologia , Fármacos do Sistema Nervoso Central/uso terapêutico , Ginsenosídeos/farmacologia , Locomoção/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Psicológico/imunologia , Estresse Psicológico/psicologia
4.
Behav Brain Res ; 287: 226-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25835320

RESUMO

Neuroimmune signalling underlies addiction and comorbid depression. Clinical observations indicate that infections and chronic lesions are more frequent in drug users and elevated inflammatory states are evident in cocaine dependents. Therefore, lipopolysaccharide (LPS) and inflammatory cytokines represent an important tool for the investigation of sickness, depressive illness and addiction behaviour. A major component of addiction is the progressive and persistent increase in locomotor activity after repeated drug administration and even prolonged periods of abstinence. The aim of this study was to investigate the response of locomotor sensitization when a non-sensitizing dose of cocaine is paired with a systemic inflammatory stimulus. LPS and cocaine were administered intraperitonealy in young-adult male C57bl/6 mice during a 5-day acquisition phase. After a 48-h withdrawal period all groups were challenged with cocaine to evaluate locomotor expression. During the acquisition phase, the LPS-treated groups displayed characteristic hypolocomotion related to sickness behaviour. The low dose of cocaine did not increase the distance travelled, characterizing a non-sensitization dose. Groups that received both LPS and cocaine did not display hypolocomotion, indicating that cocaine might counteract hypolocomotion sickness behaviour. Moreover, during challenge, only these animals expressed locomotor sensitization. Our results indicate that LPS could facilitate the expression of locomotor sensitization in mice and that the immune system may modulate cocaine-induced sensitization.


Assuntos
Cocaína/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Lipopolissacarídeos/toxicidade , Locomoção/efeitos dos fármacos , Locomoção/imunologia , Animais , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Distribuição Aleatória
5.
Brain Behav Immun ; 35: 43-50, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24026015

RESUMO

Sickness behaviors and fever during infection constitute an adaptive and tightly regulated mechanism designed to efficiently clear the invading pathogen from the body. Recent literature has demonstrated that changes in energy status can profoundly affect the fever response to an acute immune challenge. The purpose of the present study was to investigate whether the exacerbating effect of diet induced obesity (DIO) on the LPS-induced fever response demonstrated previously would generalize to other sickness behaviors and, further, whether incremental changes in body weight would influence these responses. Results showed that DIO male Wistar rats exhibited a higher number of sickness symptoms for a longer period after lipopolysaccharide (LPS) injection (100µg/kg) than lean rats. Similarly, they showed a more prolonged fever and a delayed recovery from LPS-induced suppression of social interaction. No difference in locomotor activity was observed between obese and lean groups. Comparisons among groups that varied in body weight showed that an 11% increase in body weight was sufficient to increase the number and duration of sickness symptoms displayed after an LPS-injection and that the severity of sickness symptoms increased with increasing body weight. Together these data suggest that DIO can have profound effects on multiple behavioral responses to an acute immune challenge placing obese organisms at higher risk of the consequences of prolonged inflammation.


Assuntos
Comportamento de Doença/fisiologia , Obesidade/imunologia , Obesidade/fisiopatologia , Comportamento Social , Animais , Dieta Hiperlipídica/efeitos adversos , Comportamento de Doença/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Locomoção/efeitos dos fármacos , Locomoção/imunologia , Masculino , Ratos , Ratos Wistar
6.
J Immunol ; 187(12): 6447-55, 2011 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-22079982

RESUMO

Although NLRC4/IPAF activation by flagellin has been extensively investigated, the downstream signaling pathways and the mechanisms responsible for infection clearance remain unclear. In this study, we used mice deficient for the inflammasome components in addition to wild-type (WT) Legionella pneumophila or bacteria deficient for flagellin (flaA) or motility (fliI) to assess the pathways responsible for NLRC4-dependent growth restriction in vivo and ex vivo. By comparing infections with WT L. pneumophila, fliI, and flaA, we found that flagellin and motility are important for the colonization of the protozoan host Acanthamoeba castellanii. However, in macrophages and mammalian lungs, flagellin expression abrogated bacterial replication. The flagellin-mediated growth restriction was dependent on NLRC4, and although it was recently demonstrated that NLRC4 is able to recognize bacteria independent of flagellin, we found that the NLRC4-dependent restriction of L. pneumophila multiplication was fully dependent on flagellin. By examining infected caspase-1(-/-) mice and macrophages with flaA, fliI, and WT L. pneumophila, we could detect greater replication of flaA, which suggests that caspase-1 only partially accounted for flagellin-dependent growth restriction. Conversely, WT L. pneumophila multiplied better in macrophages and mice deficient for NLRC4 compared with that in macrophages and mice deficient for caspase-1, supporting the existence of a novel caspase-1-independent response downstream of NLRC4. This response operated early after macrophage infection and accounted for the restriction of bacterial replication within bacteria-containing vacuoles. Collectively, our data indicate that flagellin is required for NLRC4-dependent responses to L. pneumophila and that NLRC4 triggers caspase-1-dependent and -independent responses for bacterial growth restriction in macrophages and in vivo.


Assuntos
Acanthamoeba castellanii/microbiologia , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Transporte/fisiologia , Flagelos/imunologia , Legionella pneumophila/crescimento & desenvolvimento , Legionella pneumophila/imunologia , Macrófagos/imunologia , Macrófagos/microbiologia , Acanthamoeba castellanii/enzimologia , Acanthamoeba castellanii/imunologia , Animais , Proteínas Reguladoras de Apoptose/deficiência , Proteínas Reguladoras de Apoptose/genética , Carga Bacteriana/imunologia , Proteínas de Bactérias/genética , Células da Medula Óssea/enzimologia , Células da Medula Óssea/imunologia , Células da Medula Óssea/microbiologia , Proteínas de Ligação ao Cálcio/deficiência , Proteínas de Ligação ao Cálcio/genética , Proteínas de Transporte/genética , Linhagem Celular , Feminino , Flagelos/enzimologia , Flagelos/genética , Flagelina/biossíntese , Flagelina/genética , Inflamassomos/deficiência , Inflamassomos/genética , Legionella pneumophila/genética , Locomoção/imunologia , Macrófagos/enzimologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR , ATPases Translocadoras de Prótons/genética , Transdução de Sinais/genética , Transdução de Sinais/imunologia
7.
Exp Gerontol ; 46(8): 643-59, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21453768

RESUMO

Aging in humans is associated with parallel changes in cognition, motivation, and motoric performance. Based on the human aging literature, we hypothesized that this constellation of age-related changes is mediated by the medial prefrontal cortex and that it would be observed in aging mice. Toward this end, we performed detailed assessments of cognition, motivation, and motoric behavior in aging mice. We assessed behavioral and cognitive performance in C57Bl/6 mice aged 6, 18, and 24 months, and followed this with microarray analysis of tissue from the medial prefrontal cortex and analysis of serum cytokine levels. Multivariate modeling of these data suggested that the age-related changes in cognition, motivation, motor performance, and prefrontal immune gene expression were highly correlated. Peripheral cytokine levels were also correlated with these variables, but less strongly than measures of prefrontal immune gene upregulation. To determine whether the observed immune gene expression changes were due to prefrontal microglial cells, we isolated CD11b-positive cells from the prefrontal cortex and subject them to next-generation RNA sequencing. Many of the immune changes present in whole medial prefrontal cortex were enriched in this cell population. These data suggest that, as in humans, cognition, motivation, and motoric performance in the mouse change together with age and are strongly associated with CNS immune gene upregulation.


Assuntos
Envelhecimento , Cognição , Regulação da Expressão Gênica , Locomoção , Motivação , Córtex Pré-Frontal/fisiologia , Desempenho Psicomotor , Envelhecimento/genética , Envelhecimento/imunologia , Animais , Cognição/fisiologia , Regulação da Expressão Gênica/genética , Locomoção/genética , Locomoção/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Motivação/fisiologia , Desempenho Psicomotor/fisiologia , Regulação para Cima
8.
Mol Ther ; 19(3): 612-9, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21206484

RESUMO

Based on the concept that anticocaine antibodies could prevent inhaled cocaine from reaching its target receptors in the brain, an effective anticocaine vaccine could help reverse cocaine addiction. Leveraging the knowledge that E1(-)E3(-) adenovirus (Ad) gene transfer vectors are potent immunogens, we have developed a novel vaccine platform for addictive drugs by covalently linking a cocaine analog to the capsid proteins of noninfectious, disrupted Ad vector. The Ad-based anticocaine vaccine evokes high-titer anticocaine antibodies in mice sufficient to completely reverse, on a persistent basis, the hyperlocomotor activity induced by intravenous administration of cocaine.


Assuntos
Cocaína/análogos & derivados , Cocaína/imunologia , Transtornos Relacionados ao Uso de Substâncias , Vacinas , Adenoviridae/genética , Animais , Anticorpos/sangue , Cocaína/metabolismo , Vírus Defeituosos/genética , Vírus Defeituosos/imunologia , Vírus Defeituosos/metabolismo , Feminino , Técnicas de Transferência de Genes , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Locomoção/efeitos dos fármacos , Locomoção/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Atividade Motora/efeitos dos fármacos , Atividade Motora/imunologia , Transtornos Relacionados ao Uso de Substâncias/imunologia , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Vacinas/administração & dosagem , Vacinas/imunologia
9.
Biotechnol Lett ; 31(9): 1353-60, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19466558

RESUMO

Pseudomonas aeruginosa as an opportunistic pathogen causes lethal infections in immunocompromised individuals. This bacterium possesses a polar flagellum made up of flagellin subunits. Flagella have important roles in motility, chemotaxis, and establishment of P. aeruginosa in acute phase of infections. Isolation, cloning, and expression of flagellin were aimed at in this study. Flagellin gene (fliC) of P. aeruginosa strain 8821M was isolated by PCR and cloned into a pET expression vector. The recombinant flagellin (46 kDa) was overexpressed as inclusion bodies (IBs). IBs were solubilized in guanidine hydrochloride (GuHCl) followed by affinity-purification and renatured using Ni(2+)-Sepharose resin. Recombinant flagellins reacted with the serum from a rabbit previously immunized with native flagellin. In addition, polyclonal antiserum raised against the recombinant flagellin was shown to significantly inhibit the cell motility of P. aeruginosa strain 8821M in vitro.


Assuntos
Flagelina/genética , Flagelina/isolamento & purificação , Pseudomonas aeruginosa/genética , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Cromatografia de Afinidade , Clonagem Molecular , Flagelina/química , Expressão Gênica , Lagomorpha , Locomoção/imunologia , Peso Molecular , Pseudomonas aeruginosa/imunologia
10.
Appl Environ Microbiol ; 74(22): 6867-75, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18805999

RESUMO

Campylobacter jejuni is one of the leading bacterial causes of food-borne gastroenteritis. Infection with C. jejuni is frequently acquired through the consumption of undercooked poultry or foods cross-contaminated with raw poultry. Given the importance of poultry as a reservoir for Campylobacter organisms, investigators have performed studies to understand the protective role of maternal antibodies in the ecology of Campylobacter colonization of poultry. In a previous study, chicks with maternal antibodies generated against the S3B strain of C. jejuni provided protection against Campylobacter colonization (O. Sahin, N. Luo, S. Huang, and Q. Zhang, Appl. Environ. Microbiol. 69:5372-5379, 2003). We obtained serum samples, collectively referred to as the C. jejuni S3B-SPF sera, from the previous study. These sera were determined to contain maternal antibodies that reacted against C. jejuni whole-cell lysates as judged by enzyme-linked immunosorbent assay. The antigens recognized by the C. jejuni S3B-SPF antibodies were identified by immunoblot analysis, coupled with mass spectrometry, of C. jejuni outer membrane protein extracts. This approach led to the identification of C. jejuni proteins recognized by the maternal antibodies, including the flagellin proteins and CadF adhesin. In vitro assays revealed that the C. jejuni S3B-SPF sera retarded the motility of the C. jejuni S3B homologous strain but did not retard the motility of a heterologous strain of C. jejuni (81-176). This finding provides a possible mechanism explaining why maternal antibodies confer enhanced protection against challenge with a homologous strain compared to a heterologous strain. Collectively, this study provides a list of C. jejuni proteins against which protective antibodies are generated in hens and passed to chicks.


Assuntos
Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Campylobacter jejuni/imunologia , Imunidade Materno-Adquirida , Animais , Galinhas , Immunoblotting , Locomoção/imunologia , Espectrometria de Massas
11.
Infect Immun ; 76(9): 4137-44, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18625740

RESUMO

Secretory immunoglobulin A (SIgA) antibodies directed against the O antigen of lipopolysaccharide (LPS) are the primary determinants of mucosal immunity to gram-negative enteric pathogens. However, the underlying mechanisms by which these antibodies interfere with bacterial colonization and invasion of intestinal epithelial cells are not well understood. In this study, we report that Sal4, a protective, anti-O5-specific monoclonal IgA, is a potent inhibitor of Salmonella enterica serovar Typhimurium flagellum-based motility. Using video light microscopy, we observed that Sal4 completely and virtually instantaneously "paralyzed" laboratory and clinical strains of serovar Typhimurium. Sal4-mediated motility arrest preceded and occurred independently of agglutination. Polyclonal anti-LPS IgG antibodies and F(ab)(2) fragments were as potent as was Sal4 at impeding bacterial motility, whereas monovalent Fab fragments were 5- to 10-fold less effective. To determine whether motility arrest can fully account for Sal4's protective capacity in vitro, we performed epithelial cell infection assays in which the requirement for flagellar motility in adherence and invasion was bypassed by centrifugation. Under these conditions, Sal4-treated serovar Typhimurium cells remained noninvasive, revealing that the monoclonal IgA, in addition to interfering with motility, has an effect on bacterial uptake into epithelial cells. Sal4 did not, however, inhibit bacterial uptake into mouse macrophages, indicating that the antibody interferes specifically with Salmonella pathogenicity island 1 (SPI-1)-dependent, but not SPI-1-independent, entry into host cells. These results reveal a previously unrecognized capacity of SIgA to "disarm" microbial pathogens on mucosal surfaces and prevent colonization and invasion of the intestinal epithelium.


Assuntos
Anticorpos Antibacterianos/imunologia , Anticorpos Monoclonais/imunologia , Células Epiteliais/microbiologia , Imunoglobulina A/imunologia , Locomoção/imunologia , Salmonella typhimurium/imunologia , Animais , Linhagem Celular , Cães , Humanos , Fragmentos Fab das Imunoglobulinas/imunologia , Macrófagos/microbiologia , Camundongos , Microscopia de Vídeo
12.
Patol Fiziol Eksp Ter ; (4): 13-4, 2008.
Artigo em Russo | MEDLINE | ID: mdl-19202615

RESUMO

The experiments on mice C57B1/6 with MPTP-induced Parkinsonian syndrome have shown that preliminary and simultaneous intranasal injection of glutamate antibodies inhibit development of the syndrome. Administration of glutamate antibodies decreased tremor, rigidity and increased horizontal locomotion, movement velocity in the open field.


Assuntos
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Anticorpos/farmacologia , Ácido Glutâmico , Intoxicação por MPTP/tratamento farmacológico , Neurotoxinas/toxicidade , Animais , Anticorpos/imunologia , Ácido Glutâmico/imunologia , Locomoção/efeitos dos fármacos , Locomoção/imunologia , Intoxicação por MPTP/imunologia , Camundongos , Síndrome , Tremor/tratamento farmacológico , Tremor/imunologia
13.
Artigo em Russo | MEDLINE | ID: mdl-17163137

RESUMO

Influence of Lactobacillus on the migration activity of intact macrophages during their cultivation with serum and supernatant of cells from Peyer's patches and spleen that were obtained from mice of CBA line orally sensibilized with lactobacteria was studied. Data about stimulation of production of factor inhibiting migration of macrophages by immunocompetent cells and development of delayed-hypersensivity reaction are obtained. Mechanisms of complex influence of lactobacteria on cell factors of innate and adaptive immunity are discussed.


Assuntos
Lactobacillus/imunologia , Fatores Inibidores da Migração de Macrófagos/imunologia , Macrófagos Peritoneais/imunologia , Nódulos Linfáticos Agregados/imunologia , Baço/imunologia , Animais , Células Cultivadas , Meios de Cultivo Condicionados/metabolismo , Hipersensibilidade Tardia , Soros Imunes/imunologia , Locomoção/imunologia , Fatores Inibidores da Migração de Macrófagos/metabolismo , Macrófagos Peritoneais/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos CBA , Nódulos Linfáticos Agregados/metabolismo , Baço/metabolismo
14.
Infect Immun ; 73(9): 6075-84, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16113328

RESUMO

Swarming migration of Serratia marcescens requires both flagellar motility and cellular differentiation and is a population-density-dependent behavior. While the flhDC and quorum-sensing systems have been characterized as important factors regulating S. marcescens swarming, the underlying molecular mechanisms are currently far from being understood. Serratia swarming is thermoregulated and is characterized by continuous surface migration on rich swarming agar surfaces at 30 degrees C but not at 37 degrees C. To further elucidate the mechanisms, identification of specific and conserved regulators that govern the initiation of swarming is essential. We performed transposon mutagenesis to screen for S. marcescens strain CH-1 mutants that swarmed at 37 degrees C. Analysis of a "precocious-swarming" mutant revealed that the defect in a conserved dapA(Sm)-nlpB(Sm) genetic locus which is closely related to the synthesis of bacterial cell wall peptidoglycan is responsible for the aberrant swarming phenotype. Further complementation and gene knockout studies showed that nlpB(Sm), which encodes a membrane lipoprotein, NlpB(Sm), but not dapA(Sm), is specifically involved in swarming regulation. On the other hand, dapA(Sm) but not nlpB(Sm) is responsible for the determination of cell envelope architecture, regulation of hemolysin production, and cellular attachment capability. While the nlpB(Sm) mutant showed similar cytotoxicity to its parent strain, the dapA(Sm) mutant significantly increased in cytotoxicity. We present evidence that DapA(Sm) is involved in the determination of cell-envelope-associated phenotypes and that NlpB(Sm) is involved in the regulation of swarming motility.


Assuntos
Aderência Bacteriana/genética , Proteínas Hemolisinas/biossíntese , Lipoproteínas/genética , Locomoção , Proteínas de Membrana/genética , Serratia marcescens/genética , Aderência Bacteriana/fisiologia , Parede Celular/genética , Elementos de DNA Transponíveis , Marcadores Genéticos , Humanos , Lipoproteínas/fisiologia , Locomoção/genética , Locomoção/imunologia , Proteínas de Membrana/fisiologia , Microscopia Eletrônica de Varredura , Dados de Sequência Molecular , Mutação , Serratia marcescens/fisiologia , Serratia marcescens/ultraestrutura
15.
Eur J Neurosci ; 16(9): 1731-40, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12431226

RESUMO

Immune cells have been shown to contribute to spontaneous recovery from central nervous system (CNS) injury. Here we show that adult female rats and mice recover significantly better than their male littermates from incomplete spinal cord injury (ISCI). This sexual dimorphism is wiped out and recovery is worse in adult mice deprived of mature T cells. After spinal cord contusion in adult rats, functional recovery (measured by locomotor scores in an open field) was significantly worse in females treated with dihydrotestosterone prior to the injury than in placebo-treated controls, and significantly better in castrated males than in their noncastrated male littermates. Post-traumatic administration of the testosterone receptor antagonist flutamide promoted the functional recovery in adult male rats. These results, in line with the known inhibitory effect of testosterone on cell-mediated immunity, suggest that androgen-mediated immunosuppression plays a role in ISCI-related immune dysfunction and can therefore partly explain the worse outcome of ISCI in males than in female. We suggest that females, which are more prone to develop autoimmune response than males, benefit from this response in cases of CNS insults.


Assuntos
Autoimunidade , Recuperação de Função Fisiológica/imunologia , Traumatismos da Medula Espinal/imunologia , Antagonistas de Androgênios/farmacologia , Animais , Castração , Di-Hidrotestosterona/farmacologia , Feminino , Flutamida/farmacologia , Locomoção/efeitos dos fármacos , Locomoção/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Fatores Sexuais , Traumatismos da Medula Espinal/patologia
17.
Brain Behav Immun ; 13(3): 252-65, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10469526

RESUMO

Influenza infection or administration of bacterial endotoxin (lipopolysaccharide, LPS) results in diminished feeding and loss of body weight. It has been suggested that these effects may be mediated by cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6), and/or tumor necrosis factor-alpha (TNFalpha). To assess the potential role of these cytokines, we tested the ability of the naturally occurring IL-1-receptor antagonist (IL-1ra), a monoclonal antibody to mouse IL-6 (IL-6mAb), and a TNF binding protein fragment (TNFbp) to antagonize hypophagia induced by intraperitoneally (ip) injected mouse IL-1beta or LPS or by inoculation with influenza virus. Feeding was assessed by measuring the daily intake of food pellets and sweetened milk in a 30-min period. The hypophagia induced by mIL-1beta or LPS was not affected by pretreatment with IL-6mAb. The effects of IL-1beta were blocked by IL-1ra but unaffected by TNFbp. TNFbp and IL-1ra given separately both exhibited a tendency to attenuate LPS-induced hypophagia. The effectiveness of TNFbp plus IL-1ra treatment was similar to that of the individual antagonists. However, combined treatment with TNFbp, IL-1ra, and IL-6mAb almost completely prevented the depressing effect of LPS on milk intake. The antagonists were also tested in influenza virus-inoculated mice. IL-1ra was delivered chronically by osmotic minipumps and was supplemented by treatment with TNFbp and IL-6mAb. The treatments slightly attenuated the effects of the virus on milk intake 48 h after the inoculation and delayed the decrease in body weight. However, over the entire course of the experiment, the treatment produced very small, statistically nonsignificant, attenuations of the depressions in milk and food pellet intake. Similar results were obtained with TNFbp alone or the combination of IL-6mAb and TNFbp. The results suggest that IL-1beta, TNFalpha, and IL-6 contribute to the hypophagia induced by LPS. However, antagonism of all three cytokines was not sufficient to prevent the decreases in feeding and loss of body weight induced by influenza virus infection.


Assuntos
Comportamento Alimentar/fisiologia , Interleucina-1/imunologia , Interleucina-6/imunologia , Infecções por Orthomyxoviridae/imunologia , Fator de Necrose Tumoral alfa/imunologia , Animais , Anticorpos Monoclonais/farmacologia , Antirreumáticos/farmacologia , Peso Corporal/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Proteína Antagonista do Receptor de Interleucina 1 , Lipopolissacarídeos/farmacologia , Locomoção/imunologia , Masculino , Camundongos , Camundongos Endogâmicos , Leite , Infecções por Orthomyxoviridae/dietoterapia , Receptores de Interleucina-1/antagonistas & inibidores , Receptores do Fator de Necrose Tumoral/imunologia , Receptores Tipo I de Fatores de Necrose Tumoral , Sialoglicoproteínas/farmacologia , Receptores Chamariz do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa/antagonistas & inibidores
18.
J Gen Psychol ; 126(2): 205-16, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10368944

RESUMO

The author's goal was to discover if the generation and maintenance of the specific immune response resulted in alterations of reliable behaviors (i.e., behaviors correlated over time). The behaviors (ambulation, rearing, and interaction with a conspecific) of CD1 male mice were measured in a small open field, and several days later, the mice were immunized with antigens (either splenocytes from C57BL/6 mice or a mixture of sheep erythrocytes and goat serum). The same behaviors were recorded again some hours, or some days, after immunization. Immunizations and behavioral measurements were repeated at various intervals. Blood levels of antibodies to the antigens were measured 6 days after immunization. The recorded behaviors were consistent (according to Kendall coefficient of concordance). The mice mounted antibody responses to the antigens, yet no behavioral changes were apparent during the response. On the contrary, a single injection of E. coli lipopolysaccharide decreased ambulation and rearing. It is proposed that in healthy mice kept in normal conditions, the specific immune response may be unrelated to reliable behavioral changes.


Assuntos
Comportamento Animal/fisiologia , Imunidade Celular/fisiologia , Animais , Locomoção/imunologia , Masculino , Camundongos , Camundongos Endogâmicos , Distribuição Aleatória , Comportamento Sexual Animal/fisiologia
19.
Genetica ; 104(3): 249-57, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-10386391

RESUMO

Behavioural studies of MHC-congenic mice and rats have focused primarily on mate choice and the ability to discriminate between strains by their urine odours, but these strains may differ in other behaviours, such as activity and ultrasonic vocalizations. Ivanyi (1978, Proc. Roy. Soc. Lord. 202, 117-158) has reviewed the physiological differences associated with the MHC, many of which could influence behaviour. We have started a systematic study of behavioural development and adult behaviour in MHC-congenic mice. A developmental test battery (growth, rate, locomotion, grooming, eye opening, ultrasonic vocalizations, etc.) was used to examine differences between C57BL/6J vs. B6-H-2bml and C57BL/10SnJ vs. B10.BR/sgSnJ mice. A test battery of spontaneous behaviours (activity, exploration, ultrasonic vocalizations, etc.) was used to examine behavioural differences between adult C57BL/6J vs. B6-H-2bml; and C57BL/10SnJ vs. B10.BR/sgSnJ mice. Differences in development and in adult behaviours between these MHC-congenic strains is discussed in relation to possible neural, endocrine and immune system differences. Future studies will compare MHC-congenic mice on levels of anxiety, sociosexual behaviour and on learning paradigms.


Assuntos
Comportamento Animal/fisiologia , Complexo Principal de Histocompatibilidade/genética , Camundongos Congênicos/fisiologia , Animais , Animais Congênicos , Animais Recém-Nascidos/genética , Animais Recém-Nascidos/crescimento & desenvolvimento , Animais Recém-Nascidos/imunologia , Peso Corporal/genética , Peso Corporal/imunologia , Defecação/genética , Defecação/imunologia , Comportamento Exploratório/fisiologia , Feminino , Asseio Animal/fisiologia , Antígenos de Histocompatibilidade Classe I/genética , Locomoção/genética , Locomoção/imunologia , Complexo Principal de Histocompatibilidade/imunologia , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Congênicos/genética , Camundongos Congênicos/imunologia , Camundongos Endogâmicos C57BL , Ratos , Ratos Endogâmicos , Micção/genética , Micção/imunologia , Vocalização Animal/fisiologia
20.
Brain Res ; 776(1-2): 96-104, 1997 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-9439800

RESUMO

Following infection with influenza virus, animals display decreased locomotor activity and feeding behavior and loss of body weight. It has been suggested that these effects may be mediated by cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), induced by the infection. To assess the potential role of IL-1, we tested the ability of a naturally occurring IL-1-receptor antagonist (IL-1ra) to antagonize the changes in feeding behavior induced by IL-1, endotoxin (lipopolysaccharide, LPS), and infection with influenza virus. Feeding behavior was assessed by measuring the daily intake of food pellets and sweetened milk in a 30-min period. Acute injection of IL-1 beta decreased milk intake, but mouse IL-6 and mouse TNF-alpha did not. However, TNF-alpha decreased food pellet intake slightly, especially when it was injected at the beginning of the dark phase. The reductions in milk intake induced by mouse IL-1 beta were largely prevented by IL-1ra pretreatment (100 micrograms/mouse i.p.). The LPS-induced reductions in milk intake were attenuated, but not blocked, by IL-1ra treatment (300 micrograms/mouse). LPS still induced significant decrements in the presence of the antagonist. In influenza virus-infected mice, IL-1ra was administered either by repeated subcutaneous (s.c.) injections, or by continuous s.c. infusion from osmotic minipumps. These IL-1ra treatments produced small, but statistically significant, attenuations of the depression in milk and food pellet intake in the virus-infected mice. In several experiments, IL-1ra treatment increased the survival of influenza virus-infected mice. Thus the attenuation of the hypophagia may have been caused by this IL-1ra-induced increase in survival. The results suggest that IL-1 contributes to sickness behavior induced by LPS and influenza virus infection, but it is not the only factor involved.


Assuntos
Comportamento Animal/fisiologia , Citocinas/fisiologia , Lipopolissacarídeos/farmacologia , Infecções por Orthomyxoviridae/imunologia , Sialoglicoproteínas/farmacologia , Animais , Apetite/efeitos dos fármacos , Apetite/imunologia , Comportamento Animal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/imunologia , Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-1/farmacologia , Interleucina-6/farmacologia , Locomoção/efeitos dos fármacos , Locomoção/imunologia , Masculino , Camundongos , Camundongos Endogâmicos , Leite , Receptores de Interleucina-1/antagonistas & inibidores , Proteínas Recombinantes/farmacologia , Fator de Necrose Tumoral alfa/farmacologia
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