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1.
Development ; 150(22)2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37997920

RESUMO

Optical insulation of the unit eyes (ommatidia) is an important prerequisite of precise sight with compound eyes. Separation of the ommatidia is ensured by pigment cells that organize into a hexagonal lattice in the Drosophila eye, forming thin walls between the facets. Cell adhesion, mediated by apically and latero-basally located junctional complexes, is crucial for stable attachment of these cells to each other and the basal lamina. Whereas former studies have focused on the formation and remodelling of the cellular connections at the apical region, here, we report a specific alteration of the lateral adhesion of the lattice cells, leaving the apical junctions largely unaffected. We found that DAAM and FRL, two formin-type cytoskeleton regulatory proteins, play redundant roles in lateral adhesion of the interommatidial cells and patterning of the retinal floor. We show that formin-dependent cortical actin assembly is crucial for latero-basal sealing of the ommatidial lattice. We expect that the investigation of these previously unreported eye phenotypes will pave the way toward a better understanding of the three-dimensional aspects of compound eye development.


Assuntos
Proteínas de Drosophila , Animais , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Forminas/metabolismo , Drosophila/metabolismo , Citoesqueleto/metabolismo , Retina/metabolismo , Olho/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo
2.
PLoS Pathog ; 11(7): e1004994, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26147567

RESUMO

Parasitic helminths establish chronic infections in mammalian hosts. Helminth/Plasmodium co-infections occur frequently in endemic areas. However, it is unclear whether Plasmodium infections compromise anti-helminth immunity, contributing to the chronicity of infection. Immunity to Plasmodium or helminths requires divergent CD4+ T cell-driven responses, dominated by IFNγ or IL-4, respectively. Recent literature has indicated that Th cells, including Th2 cells, have phenotypic plasticity with the ability to produce non-lineage associated cytokines. Whether such plasticity occurs during co-infection is unclear. In this study, we observed reduced anti-helminth Th2 cell responses and compromised anti-helminth immunity during Heligmosomoides polygyrus and Plasmodium chabaudi co-infection. Using newly established triple cytokine reporter mice (Il4gfpIfngyfpIl17aFP635), we demonstrated that Il4gfp+ Th2 cells purified from in vitro cultures or isolated ex vivo from helminth-infected mice up-regulated IFNγ following adoptive transfer into Rag1-/- mice infected with P. chabaudi. Functionally, Th2 cells that up-regulated IFNγ were transcriptionally re-wired and protected recipient mice from high parasitemia. Mechanistically, TCR stimulation and responsiveness to IL-12 and IFNγ, but not type I IFN, was required for optimal IFNγ production by Th2 cells. Finally, blockade of IL-12 and IFNγ during co-infection partially preserved anti-helminth Th2 responses. In summary, this study demonstrates that Th2 cells retain substantial plasticity with the ability to produce IFNγ during Plasmodium infection. Consequently, co-infection with Plasmodium spp. may contribute to the chronicity of helminth infection by reducing anti-helminth Th2 cells and converting them into IFNγ-secreting cells.


Assuntos
Coinfecção/imunologia , Interferon gama/metabolismo , Interleucina-12/imunologia , Malária/imunologia , Infecções por Strongylida/imunologia , Células Th2/imunologia , Transferência Adotiva , Animais , Separação Celular , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Interferon gama/imunologia , Ativação Linfocitária/imunologia , Camundongos , Camundongos Knockout , Nematospiroides dubius/imunologia , Plasmodium chabaudi/imunologia , Reação em Cadeia da Polimerase
3.
J Immunol ; 193(9): 4602-13, 2014 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-25261485

RESUMO

IL-22 is a cytokine that regulates tissue homeostasis at barrier surfaces. A variety of IL-22-producing cell types is known, but identification on the single-cell level remains difficult. Therefore, we generated a fate reporter mouse that would allow the identification of IL-22-producing cells and their fate mapping in vivo. To trace IL-22-expressing cells, a sequence encoding Cre recombinase was cloned into the Il22 locus, and IL22(Cre) mice were crossed with reporter mice expressing enhanced yellow fluorescence protein (eYFP) under control of the endogenous Rosa26 promoter. In IL22(Cre)R26R(eYFP) mice, the fluorescent reporter permanently labels cells that have switched on Il22 expression, irrespective of cytokine production. Despite a degree of underreporting, eYFP expression was detectable in nonimmune mice and restricted to group 3 innate lymphoid cells (ILC3) in the gut and γδ T cells in skin or lung. Upon skin challenge with imiquimod, eYFP(+) γδ and CD4 T cells expanded in the skin. Infection with Citrobacter rodentium initially was controlled by ILC3, followed by expansion of eYFP(+) CD4 T cells, which were induced in innate lymphoid follicles in the colon. No eYFP expression was detected in small intestinal Th17 cells, and they did not expand in the immune response. Colonic eYFP(+) CD4 T cells exhibited plasticity during infection with expression of additional cytokines, in contrast to ILC3, which remained largely stable. Single-cell quantitative PCR analysis of eYFP(+) CD4 T cells confirmed their heterogeneity, suggesting that IL-22 expression is not confined to particular subsets or a dedicated Th22 subset.


Assuntos
Homeostase , Infecções/metabolismo , Interleucinas/biossíntese , Animais , Citrobacter rodentium/imunologia , Análise por Conglomerados , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Infecções por Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/metabolismo , Expressão Gênica , Perfilação da Expressão Gênica , Ordem dos Genes , Marcação de Genes , Genes Reporter , Loci Gênicos , Homozigoto , Infecções/imunologia , Inflamação/genética , Inflamação/imunologia , Inflamação/metabolismo , Interleucinas/genética , Linfócitos/imunologia , Linfócitos/metabolismo , Camundongos , Camundongos Transgênicos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Interleucina 22
4.
PLoS Pathog ; 9(6): e1003406, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23762028

RESUMO

Resolution of a variety of acute bacterial and parasitic infections critically relies on the stimulation of myelopoiesis leading in cases to extramedullary hematopoiesis. Here, we report the isolation of the earliest myeloid-restricted progenitors in acute infection with the rodent malaria parasite, Plasmodium chabaudi. The rapid disappearance of these infection-induced myeloid progenitors from the bone marrow (BM) equated with contraction of the functional myeloid potential in that organ. The loss of BM myelopoiesis was not affected by the complete genetic inactivation of toll-like receptor signaling. De-activation of IFN-γ signaling completely abrogated the contraction of BM myeloid progenitors. Radiation chimeras of Ifngr1-null and control BM revealed that IFN-γ signaling in an irradiation-resistant stromal compartment was crucial for the loss of early myeloid progenitors. Systemic IFN-γ triggered the secretion of C-C motif ligand chemokines CCL2 and CCL7 leading to the egress of early, myeloid-committed progenitors from the bone marrow mediated by their common receptor CCR2. The mobilization of myeloid progenitors initiated extramedullary myelopoiesis in the spleen in a CCR2-dependent manner resulting in augmented myelopoiesis during acute malaria. Consistent with the lack of splenic myelopoiesis in the absence of CCR2 we observed a significant persistence of parasitemia in malaria infected CCR2-deficient hosts. Our findings reveal how the activated immune system mobilizes early myeloid progenitors out of the BM thereby transiently establishing myelopoiesis in the spleen in order to contain and resolve the infection locally.


Assuntos
Quimiocina CCL2/imunologia , Quimiocina CCL7/imunologia , Hematopoese Extramedular/imunologia , Interferon gama/imunologia , Malária/imunologia , Células Progenitoras Mieloides/imunologia , Mielopoese/imunologia , Plasmodium chabaudi/imunologia , Animais , Quimiocina CCL2/genética , Quimiocina CCL7/genética , Interferon gama/genética , Malária/genética , Camundongos , Camundongos Knockout , Receptores CCR2/genética , Receptores CCR2/imunologia , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Baço/imunologia , Receptores Toll-Like/genética , Receptores Toll-Like/imunologia
5.
Res Sq ; 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38343805

RESUMO

Pre-Pulse Inhibition (PPI) is a neural process where suppression of a startle response is elicited by preceding the startling stimulus (Pulse) with a weak, non-startling one (Pre-Pulse). Defective PPI is widely employed as a behavioural endophenotype in humans and mammalian disorder-relevant models for neuropsychiatric disorders. We have developed a user-friendly, semi-automated, high-throughput-compatible Drosophila light-off jump response PPI paradigm, with which we demonstrate that PPI, with similar parameters measured in mammals, exists in adults of this model organism. We report that Drosophila PPI is affected by reduced expression of Dysbindin and both reduced and increased expression of Nmdar1 (N-methyl-D-aspartate receptor 1), perturbations associated with schizophrenia. Studying the biology of PPI in an organism that offers a plethora of genetic tools and a complex and well characterized connectome will greatly facilitate our efforts to gain deeper insight into the aetiology of human mental disorders, while reducing the need for mammalian models.

6.
Immunogenetics ; 64(8): 591-604, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22581009

RESUMO

T cell development constitutes a multistage process allowing the dissection of events resulting in cellular commitment and functional specification in a specialized microenvironment. This process is guided by the appropriate expression of regulatory genetic factors like transcriptional activators or repressors which are, in part, dependent on instructive signals of the microenvironment. To date, it remains unclear whether exactly the same genetic mechanism acts in adult compared to fetal T cell development. In order to directly compare T cell commitment during adult and fetal differentiation, we isolated subsequent stages of intrathymic subpopulations starting with early canonical T cell progenitors up to irreversibly committed T cell precursors. The genome-wide analysis revealed several distinct gene clusters with a specific pattern of gene regulation for each subset. The largest cluster contained genes upregulated after transition through the most primitive pool into the next transitory population with a consistently elevated expression of elements associated with ongoing T cell fate specification, like Gata3 and Tcf7, in fetal progenitors. Furthermore, adult and fetal T cell progenitors occupied distinct "transcriptional territories" revealing a precise land map of the progression to final T cell commitment operating in different developmental windows. The presence and/or elevated expression of elements associated with an ongoing establishment of a T cell signature in the most primitive fetal subset is highly suggestive for an extrathymic initiation of T cell specification and underlines the fundamental differences in fetal versus adult lymphopoiesis.


Assuntos
Diferenciação Celular/genética , Linhagem da Célula/genética , Feto , Perfilação da Expressão Gênica , Linfócitos T/fisiologia , Timócitos/fisiologia , Animais , Feminino , Regulação da Expressão Gênica , Células-Tronco Hematopoéticas/fisiologia , Linfopoese , Camundongos , Camundongos Endogâmicos C57BL , Análise em Microsséries
7.
Neurochem Int ; 52(1-2): 95-102, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17719142

RESUMO

In the present study we investigated whether serotonin release in the hippocampus is subject to regulation via cannabinoid receptors. Both rat and mouse hippocampal slices were preincubated with [3H]serotonin ([3H]5-HT) and superfused with medium containing serotonin reuptake inhibitor citalopram hydrobromide (300 nM). The cannabinoid receptor agonist R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate (WIN55,212-2, 1 microM) did not affect either the resting or the electrically evoked [3H]5-HT release. In the presence of the ionotropic glutamate receptor antagonists D(-)-2-amino-5-phosphonopentanoic acid (AP-5, 50 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione-disodium (CNQX, 10 microM) the evoked [3H]5-HT release was decreased significantly. Similar findings were obtained when CNQX (10 microM) was applied alone with WIN55,212-2. This effect was abolished by the selective cannabinoid receptor subtype 1 (CB1) antagonists N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716, 1 microM) and 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide trifluoroacetate salt (AM251, 1 microM). Similarly to that observed in rats, WIN55,212-2 (1 microM) decreased the evoked [3H]5-HT efflux in wild-type mice (CB1+/+). The inhibitory effect of WIN55,212-2 (1 microM) was completely absent in hippocampal slices derived from mice genetically deficient in CB1 cannabinoid receptors (CB1-/-). Relatively selective degeneration of fine serotonergic axons by the neurotoxin parachloramphetamine (PCA) reduced significantly the tritium uptake and the evoked [3H]5-HT release. In addition, PCA, eliminated the effect of WIN55,212-2 (1 microM) on the stimulation-evoked [3H]5-HT efflux. In contrast to the PCA-treated animals, WIN55,212-2 (1 microM) reduced the [3H]5-HT efflux in the saline-treated group. Our data suggest that a subpopulation of non-synaptic serotonergic afferents express CB1 receptors and activation of these CB1 receptors leads to a decrease in 5-HT release.


Assuntos
Hipocampo/metabolismo , Receptor CB1 de Canabinoide/fisiologia , Serotonina/metabolismo , Animais , Técnicas In Vitro , Masculino , Camundongos , Ratos , Ratos Wistar , Receptor CB1 de Canabinoide/agonistas , Sinapses/metabolismo , Trítio , p-Cloroanfetamina/farmacologia
8.
Cell Signal ; 51: 266-275, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30121334

RESUMO

Trans-membrane adenylyl cyclase (tmAC) isoforms show markedly distinct regulatory properties that have not been fully explored. AC9 is highly expressed in vital organs such as the heart and the brain. Here, we report that the isoform-specific carboxyl-terminal domain (C2b) of AC9 inhibits the activation of the enzyme by Gs-coupled receptors (GsCR). In human embryonic kidney cells (HEK293) stably overexpressing AC9, cAMP production by AC9 induced upon the activation of endogenous ß-adrenergic and prostanoid GsCRs was barely discernible. Cells expressing AC9 lacking the C2b domain showed a markedly enhanced cAMP response to GsCR. Subsequent studies of the response of AC9 mutants to the activation of GsCR revealed that residues 1268-1276 in the C2b domain were critical for auto-inhibition. Two main species of AC9 of 130 K and ≥ 170 K apparent molecular weight were observed on immunoblots of rodent and human myocardial membranes with NH2-terminally directed anti-AC9 antibodies. The lower molecular weight AC9 band did not react with antibodies directed against the C2b domain. It was the predominant species of AC9 in rodent heart tissue and some of the human samples. There is a single gene for AC9 in vertebrates, moreover, amino acids 957-1353 of the COOH-terminus are encoded by a single exon with no apparent signs of mRNA splicing or editing making it highly unlikely that COOH-terminally truncated AC9 could arise through the processing or editing of mRNA. Thus, deductive reasoning leads to the suggestion that proteolytic cleavage of the C2b auto-inhibitory domain may govern the activation of AC9 by GsCR.


Assuntos
Adenilil Ciclases/metabolismo , Membrana Celular/metabolismo , Giro do Cíngulo/metabolismo , Hipocampo/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Adenilil Ciclases/genética , Animais , AMP Cíclico/metabolismo , Células HEK293 , Ventrículos do Coração/metabolismo , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Domínios Proteicos , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais
9.
Acta Vet Hung ; 54(4): 437-48, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17278716

RESUMO

Increasing use of Mycoplasma gallisepticum (MG) live vaccines has led to a need for the differentiation of MG strains. The MG strains MK-7, MS-16, S6, FS-9 and R strains and the MG live vaccine strain F were compared by random amplification of polymorphic DNA (RAPD) in this study. Using RAPD, different patterns were found among the MG strains. In addition to this, we examined the differentiating potential of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) primers targeted at the crmA, crmB, crmC, gapA, mgc2 and pvpA genes encoding cytadherence-related surface proteins. These proteins may take part in the pathogenesis of MG-induced disease. Differentiation of strain F is based on the identification of restriction enzyme sites in the PCR amplicons. Using HphI enzyme, crmC PCR amplicons produced different RFLP patterns. Digestion of amplicons of gapA-specific PCR with MboI enzyme also produced distinct patterns. Differences were observed among strains R and F by digestion of mgc2 PCR amplicons with HaelIl and VspI enzymes and digestion of pvpA PCR amplicons with AccI, PvulI and ScrFI endonucleases. This method can be used for the rapid differentiation of vaccine strain from wild strains. Differentiation of MG strains is a great advantage for diagnosticians or practitioners and it is useful for epidemiological studies.


Assuntos
Vacinas Bacterianas , Infecções por Mycoplasma/veterinária , Mycoplasma gallisepticum/isolamento & purificação , Doenças das Aves Domésticas/prevenção & controle , Animais , Primers do DNA , DNA Bacteriano/análise , Infecções por Mycoplasma/prevenção & controle , Mycoplasma gallisepticum/classificação , Mycoplasma gallisepticum/genética , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Aves Domésticas , Doenças das Aves Domésticas/microbiologia , Valor Preditivo dos Testes , Sensibilidade e Especificidade
10.
Acta Vet Hung ; 54(4): 427-35, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17278715

RESUMO

A Mycoplasma bovis species-specific PCR assay has been developed with improvement of a previously described method (Ghadersohi et al., 1997). This test and its semi-nested version (Hayman and Hirst, 2003) did not function at all in our hands. A new reverse primer (Mbr2) was designed using previously published sequence data. For testing specificity, DNA was extracted from the most frequently occurring mycoplasma species and bacteria of bovine origin. The new PCR detected only Mycoplasma bovis. Moreover, no cross-reaction was observed with the genetically closest relative species, M. agalactiae. The target organism could be detected in a dose as low as 150 CFU ml(-1) in broth cultures using ethidium-bromide-stained agarose gels.


Assuntos
Doenças dos Bovinos/diagnóstico , Infecções por Mycoplasma/veterinária , Mycoplasma bovis/isolamento & purificação , Animais , Bovinos , Doenças dos Bovinos/microbiologia , Primers do DNA , DNA Bacteriano/análise , Infecções por Mycoplasma/diagnóstico , Mycoplasma bovis/genética , Reação em Cadeia da Polimerase/veterinária , Valor Preditivo dos Testes , Sensibilidade e Especificidade
11.
Acta Vet Hung ; 53(3): 299-307, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16156125

RESUMO

The capture of mycoplasmas (M. hominis, M. buccale, M. fermentans, M. bovis, M. synoviae, M. gallisepticum and M. arthritidis) based on lipid structures and adhesion molecules present in the mycoplasmal membrane was tested using different chromatographic resins (ActiClean Etox, ClarEtox, Heparin-Actigel, Sulfated Hiflow and SulfEtox). All of the resins efficiently reduced mycoplasma concentrations in Phosphate Buffered Saline (PBS) and in Fetal Bovine Serum (FBS) by 3-8 logs in a few minutes. This technology could be used for removing mycoplasmas from tissue culture components such as serum, and for concentrating mycoplasmas in vaccine production.


Assuntos
Aderência Bacteriana/fisiologia , Mycoplasma/isolamento & purificação , Mycoplasma/fisiologia , Resinas Sintéticas , Adsorção , Moléculas de Adesão Celular/fisiologia , Membrana Celular/fisiologia , Cromatografia
12.
Microbes Infect ; 6(6): 536-41, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15158186

RESUMO

The in vivo action of the antimicrobial peptide melittin, expressed from a recombinant plasmid vector, on chickens experimentally infected with Mycoplasma gallisepticum was studied. The plasmid vector pBI/mel2/rtTA includes the melittin gene under the control of an inducible tetracycline-dependent human cytomegalovirus promoter and the gene coding for the trans-activation protein rtTA. Aerosol administration of the vector, followed by infecting the chickens with M. gallisepticum 1226, is shown to inhibit development of infection. The inhibitory action was confirmed by a complex of clinical, pathomorphological, histological and serological studies, and also by comparing the M. gallisepticum reisolation frequency from the respiratory tract and internal organs. The data suggest that plasmid vectors expressing genes of antimicrobial peptides can be considered as potential agents for the prevention and treatment of mycoplasma infections in poultry farming.


Assuntos
Terapia Genética/veterinária , Meliteno/genética , Infecções por Mycoplasma/veterinária , Mycoplasma gallisepticum , Doenças das Aves Domésticas/prevenção & controle , Sacos Aéreos/microbiologia , Sacos Aéreos/patologia , Animais , Anticorpos Antibacterianos/sangue , Galinhas , Vetores Genéticos , Coração/microbiologia , Rim/microbiologia , Rim/patologia , Fígado/microbiologia , Fígado/patologia , Pulmão/microbiologia , Pulmão/patologia , Infecções por Mycoplasma/microbiologia , Infecções por Mycoplasma/patologia , Infecções por Mycoplasma/prevenção & controle , Mycoplasma gallisepticum/imunologia , Mycoplasma gallisepticum/isolamento & purificação , Plasmídeos , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/patologia , Mucosa Respiratória , Baço/microbiologia , Baço/patologia , Traqueia/microbiologia , Traqueia/patologia
13.
Neuropharmacology ; 64: 254-63, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22824189

RESUMO

Classical antipsychotics, e.g. haloperidol, chlorpromazine, are potent at controlling the positive symptoms of schizophrenia but frequently elicit extrapyramidal motor side-effects. The introduction of atypical antipsychotics such as risperidone, olanzapine and clozapine has obviated this problem, but none of the current drugs seem to improve the cognitive deficits accompanying schizophrenia. Thus there is an unmet need for agents that not only suppress the psychotic symptoms but also ameliorate the impairment of cognition. Here, we report the preclinical properties of a candidate antipsychotic, Egis-11150, that shows marked pro-cognitive efficacy. Egis-11150 displayed high affinity for adrenergic α(1), α(2c), 5-HT(2A) 5-HT7, moderate affinity for adrenergic α(2a) and D2 receptors. It was a functional antagonist on all of the above receptors, with the exception of 5-HT7 receptors, where it was an inverse agonist. Phencyclidine-induced hypermotility in mice and inhibition of conditioned avoidance response in rats were assessed to estimate efficacy against the positive and social withdrawal test in rats was used to predict efficacy against the negative symptoms of schizophrenia. Passive-avoidance learning, novel object recognition and radial maze tests in rats were used to assess pro-cognitive activity, while phencyclidine-induced disruption of prepulse inhibition in mice was examined to test for effects on attention. Egis-11150 (0.01-0.3 mg/kg, ip.) was effective in all of the preclinical models of schizophrenia examined. Moreover, a robust pro-cognitive profile was apparent. In summary, work in preclinical models indicates that Egis-11150 is a potential treatment for controlling the psychosis as well as the cognitive dysfunction in schizophrenia. This article is part of a Special Issue entitled 'Cognitive Enhancers'.


Assuntos
Antipsicóticos/uso terapêutico , Transtornos Cognitivos/prevenção & controle , Drogas em Investigação/uso terapêutico , Nootrópicos/uso terapêutico , Piperidinas/uso terapêutico , Piridazinas/uso terapêutico , Esquizofrenia/tratamento farmacológico , Antagonistas de Receptores Adrenérgicos alfa 1/administração & dosagem , Antagonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Animais , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Comportamento Animal/efeitos dos fármacos , Transtornos Cognitivos/etiologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Drogas em Investigação/administração & dosagem , Drogas em Investigação/efeitos adversos , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos , Nootrópicos/administração & dosagem , Nootrópicos/efeitos adversos , Piperidinas/administração & dosagem , Piperidinas/efeitos adversos , Piridazinas/administração & dosagem , Piridazinas/efeitos adversos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Esquizofrenia/fisiopatologia , Antagonistas do Receptor 5-HT2 de Serotonina/administração & dosagem , Antagonistas do Receptor 5-HT2 de Serotonina/efeitos adversos , Antagonistas do Receptor 5-HT2 de Serotonina/uso terapêutico
14.
Neurochem Int ; 60(2): 145-52, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22133429

RESUMO

Exogenous and endogenous cannabinoids play an important role in modulating the release of neurotransmitters in hippocampal excitatory and inhibitory networks, thus having profound effect on higher cognitive and emotional functions such as learning and memory. In this study we have studied the effect of cannabinoid agonists on the potassium depolarization-evoked [(3)H]GABA release from hippocampal synaptosomes in the wild-type (WT) and cannabinoid 1 receptor (CB(1)R)-null mutant mice. All tested cannabinoid agonists (WIN55,212-2, CP55,940, HU-210, 2-arachidonoyl-glycerol, 2-AG; delta-9-tetra-hydrocannabinol, THC) inhibited [(3)H]GABA release in WT mice with the following rank order of agonist potency: HU-210>CP55,490>WIN55,212-2>>2-AG>THC. By contrast, 2-AG and THC displayed the greatest efficacy eliciting almost complete inhibition of evoked [(3)H]GABA efflux, whereas the maximal inhibition obtained by HU-210, CP55,490, and WIN55,212-2 were less, eliciting not more than 40% inhibition. The inhibitory effect of WIN55,212-2, THC and 2-AG on evoked [(3)H]GABA efflux was antagonized by the CB(1) receptor inverse agonist AM251 (0.5 µM) in the WT mice. In the CB(1)R knockout mice the inhibitory effects of all three agonists were attenuated. In these mice, AM251 did not antagonize, but further reduced the [(3)H]GABA release in the presence of the synthetic agonist WIN55,212-2. By contrast, the concentration-dependent inhibitory effects of THC and 2-AG were partially antagonized by AM251 in the absence of CB(1) receptors. Finally, the inhibition of evoked [(3)H]GABA efflux by THC and 2-AG was also partially attenuated by AM630 (1 µM), the CB(2) receptor-selective antagonist, both in WT and CB(1) knockout mice. Our data prove the involvement of CB(1) receptors in the effect of exo- and endocannabinoids on GABA efflux from hippocampal nerve terminals. In addition, in the effect of the exocannabinoid THC and the endocannabinoid 2-AG, non-CB(1), probably CB(2)-like receptors are also involved.


Assuntos
Moduladores de Receptores de Canabinoides/fisiologia , Endocanabinoides , Hipocampo/metabolismo , Inibição Neural/fisiologia , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Canabinoides/farmacologia , Hipocampo/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos , Camundongos Knockout , Inibição Neural/genética , Terminações Pré-Sinápticas/metabolismo , Terminações Pré-Sinápticas/fisiologia , Receptor CB1 de Canabinoide/deficiência , Receptor CB1 de Canabinoide/genética , Receptor CB2 de Canabinoide/genética , Trítio
15.
Plant Physiol Biochem ; 52: 162-8, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22285370

RESUMO

SET/I(2)(PP2A), a member of the family of nucleosome assembly proteins (NAPs), has been previously described as a multifunctional protein inhibiting protein phosphatase 2A (PP2A)-mediated histone H3((pSer10)) dephosphorylation during the heat shock response in animal cells. In the present work we demonstrate that its plant orthologs, designated as NAP-related proteins (NRPs), have a similar in vitro biochemical activity and interact with PP2A and histone H3((pSer10))in vivo. Although heat shock gene promoters were found to be associated with histone H3((pSer10))-marked chromatin following a high temperature treatment, heat shock gene expression was not affected in NRP-deficient mutant Arabidopsis thaliana (L.) plantlets. These observations indicate that NRPs are potential regulators of histone dephosphorylation in plants, but they are dispensable for gene expression reorganization in response to heat shock.


Assuntos
Arabidopsis/enzimologia , Proteínas de Choque Térmico/genética , Medicago sativa/enzimologia , Nucleossomos/metabolismo , Proteína Fosfatase 2/antagonistas & inibidores , Sequência de Aminoácidos , Animais , Anticorpos , Arabidopsis/genética , Montagem e Desmontagem da Cromatina , Inibidores Enzimáticos , Expressão Gênica , Histonas/genética , Histonas/metabolismo , Temperatura Alta , Medicago sativa/genética , Dados de Sequência Molecular , Mutação , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas/genética , Proteína Fosfatase 2/genética , Proteína Fosfatase 2/metabolismo , Coelhos , Alinhamento de Sequência
16.
FEBS Lett ; 583(7): 1175-82, 2009 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-19285078

RESUMO

Plants have evolved distinct mechanisms to link Rho-type (Rop) GTPases to downstream signaling pathways as compared to other eukaryotes. Here, experimental data are provided that members of the Medicago, as well as Arabidopsis, receptor-like cytoplasmic kinase family (RLCK Class VI) were strongly and specifically activated by GTP-bound Rop GTPases in vitro. Deletion analysis indicated that the residues implicated in the interaction might be distributed on various parts of the kinases. Using a chimaeric Rop GTPase protein, the importance of the Rho-insert region in kinase activation could also be verified. These data strengthen the possibility that RLCKs may serve as Rop GTPase effectors in planta.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Medicago truncatula/enzimologia , Proteínas Quinases/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Ativação Enzimática/fisiologia , Medicago truncatula/genética , Proteínas Quinases/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas rho de Ligação ao GTP/genética
17.
Avian Pathol ; 34(4): 341-7, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16147571

RESUMO

Mycoplasma gallisepticum TS-11 vaccine was studied for its safety and protective ability in 49-day-old M. gallisepticum-free and Mycoplasma synoviae-free commercial Tetra SL layer chickens. Sixty birds were distributed into four groups: 15 were unvaccinated but were challenged with M. gallisepticum R-strain, 15 were vaccinated by eye drop and then challenged with virulent M. gallisepticum R-strain 4 weeks post vaccination, 15 were designated as controls without vaccination and challenge, and 15 received TS-11 vaccine but no challenge. Based on the post-challenge clinical signs, body weight gain, gross pathological examination of air sacs and peritoneum, histological examination of the trachea, lung, spleen and liver, and reisolation of mycoplasmas from inner organs, the TS-11 vaccine is safe and does not produce clinical signs, a major decrease of body weight gain or pathological lesions. Vaccination induced a slight serological response to M. gallisepticum antigen in serum plate agglutination and blocking enzyme-linked immunosorbent assay tests and prevented development clinical signs of airsacculitis, peribronchitis and interstitial pneumonia on M. gallisepticum challenge.


Assuntos
Vacinas Bacterianas , Galinhas/microbiologia , Infecções por Mycoplasma/veterinária , Mycoplasma gallisepticum/patogenicidade , Doenças das Aves Domésticas/prevenção & controle , Animais , Vacinas Bacterianas/efeitos adversos , Bronquite/microbiologia , Bronquite/veterinária , Feminino , Fígado/microbiologia , Linfonodos/microbiologia , Mucosa/patologia , Infecções por Mycoplasma/microbiologia , Infecções por Mycoplasma/patologia , Infecções por Mycoplasma/prevenção & controle , Mycoplasma gallisepticum/imunologia , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/veterinária , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/patologia , Traqueia/patologia , Virulência , Aumento de Peso
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