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1.
Behav Brain Res ; 465: 114956, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38479475

RESUMO

Epilepsy designates a group of chronic brain disorders, characterized by the recurrence of hypersynchronous, repetitive activity, of neuronal clusters. Epileptic seizures are the hallmark of epilepsy. The primary goal of epilepsy treatment is to eliminate seizures with minimal side effects. Nevertheless, approximately 30% of patients do not respond to the available drugs. An imbalance between excitatory/inhibitory neurotransmission, that leads to excitotoxicity, seizures, and cell death, has been proposed as an important mechanism regarding epileptogenesis. Recently, it has been shown that microreactors composed of platinum nanoparticles (Pt-NP) and glutamate dehydrogenase possess in vitro and in vivo activity against excitotoxicity. This study investigates the in vivo effects of these microreactors in an animal model of epilepsy induced by the administration of the GABAergic antagonist bicuculline. Male Wistar rats were administered intracerebroventricularly (i.c.v.) with the microreactors or saline and, five days later, injected with bicuculline or saline. Seizure severity was evaluated in an open field. Thirty min after behavioral measurements, animals were euthanized, and their brains processed for neurodegeneration evaluation and for neurogenesis. Treatment with the microreactors significantly increased the time taken for the onset of seizures and for the first tonic-clonic seizure, when compared to the bicuculline group that did not receive the microreactor. The administration of the microreactors also increased the time spent in total exploration and grooming. Treatment with the microreactors decreased bicuculline-induced neurodegeneration and increased neurogenesis in the dorsal and ventral hippocampus. These observations suggest that treatment with Pt-NP-based microreactors attenuates the behavioral and neurobiological consequences of epileptiform seizure activity.


Assuntos
Epilepsia , Nanopartículas Metálicas , Fármacos Neuroprotetores , Humanos , Ratos , Animais , Masculino , Bicuculina/farmacologia , Platina/efeitos adversos , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico
2.
Brain Res Bull ; 190: 1-11, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36089164

RESUMO

Excitotoxicity is described as the exacerbated activation of glutamate AMPA and NMDA receptors that leads to neuronal damage, and ultimately to cell death. Astrocytes are responsible for the clearance of 80-90% of synaptically released glutamate, preventing excitotoxicity. Chronic stress renders neurons vulnerable to excitotoxicity and has been associated to neuropsychiatric disorders, i.e., anxiety. Microreactors containing platinum nanoparticles (Pt-NP) and glutamate dehydrogenase have shown in vitro activity against excitotoxicity. The purpose of the present study was to investigate the in vivo effects of these microreactors on the behavioral and neurobiological effects of chronic stress exposure. Rats were either unstressed or exposed for 2 weeks to an unpredictable chronic mild stress paradigm (UCMS), administered intra-ventral hippocampus with the microreactors (with or without the blockage of astrocyte functioning), and seven days later tested in the elevated T-maze (ETM; Experiment 1). The ETM allows the measurement of two defensive responses, avoidance and escape, in terms of psychopathology respectively related to generalized anxiety and panic disorder. Locomotor activity in an open field was also measured. Since previous evidence shows that stress inhibits adult neurogenesis, we evaluated the effects of the different treatments on the number of cells expressing the marker of migrating neuroblasts doublecortin (DCX) in the dorsal and ventral hippocampus (Experiment 2). Results showed that UCMS induces anxiogenic effects, increases locomotion, and decreases the number of DCX cells in the dorsal and ventral hippocampus, effects that were counteracted by microreactor administration. This is the first study to demonstrate the in vivo efficacy of Pt-NP against the behavioral and neurobiological effects of chronic stress exposure.


Assuntos
Nanopartículas Metálicas , Platina , Animais , Ratos , Platina/metabolismo , Ratos Wistar , Neurogênese/fisiologia , Hipocampo/metabolismo , Ansiedade/tratamento farmacológico , Ansiedade/patologia , Ácido Glutâmico/metabolismo
3.
Behav Brain Res ; 356: 107-119, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30118773

RESUMO

Previous studies showed that chronic treatment with corticosterone facilitates elevated T-maze (ETM) inhibitory avoidance and a step-down avoidance task, responses that have been used to investigate aversive conditioning and memory processes. On the other hand, chronic corticosterone does not alter ETM escape from the open arms. The purpose of the present study was to further investigate the effects of chronic corticosterone treatment (200 mg pellets, 21-day release) in an animal model of anxiety that does not involve aversive conditioning: the light/dark transition model. We also investigated the pattern of ΔFosB immunoreactivity (ΔFosB-ir) in different brain regions. To examine how treatment with chronic corticosterone interferes with CRFR1 expression we measured CRFR1 in the same brain structures that exhibited increased ΔFosB-ir. Results showed that chronic treatment with corticosterone did not alter behavioral measurements performed in the light/dark transition model. On the other hand, ΔFosB-ir was increased in several structures that modulate aversive conditioning: the cingulate cortex, the ventro and dorsolateral septum, the amygdala, the paraventricular, dorsomedial and ventromedial hypothalamus, the periaqueductal grey matter, the dorsal raphe, and the median raphe nucleus. Chronic treatment with corticosterone also increased CRFR1-immunoreactivity in the ventrolateral septum, central amygdala, dorsomedial hypothalamus, ventral region of the dorsal raphe and median raphe. These results contribute to a better understanding of the behavioral and neurobiological alterations induced by chronic exposure to glucocorticoids.


Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/efeitos dos fármacos , Receptores de Hormônio Liberador da Corticotropina/efeitos dos fármacos , Animais , Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/metabolismo , Aprendizagem da Esquiva/fisiologia , Encéfalo/metabolismo , Condicionamento Psicológico , Corticosterona/farmacologia , Modelos Animais de Doenças , Reação de Fuga/fisiologia , Masculino , Memória , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-fos/imunologia , Ratos , Ratos Wistar , Receptores de Hormônio Liberador da Corticotropina/imunologia , Estresse Psicológico/metabolismo
4.
Biota Neotrop. (Online, Ed. ingl.) ; 15(4): e0095, tab, graf
Artigo em Inglês | LILACS | ID: biblio-951058

RESUMO

Spatial and temporal distribution of stream macroalgae in streams from southeastern Brazil were assessed for one year. The fluctuations in macroalgal species composition and environmental factors were monitored monthly. The region exhibit a tropical climate, with defined rainy and dry seasons. Nineteen species were found, with a predominance of Chlorophyta (52.7% of the species), followed by Cyanobacteria (26.3%), Ochrophyta and Rhodophyta (10.5% each). Scytonema arcangeli had the highest number of records (63.6%), while Mougeotia capucina occurred in all sampling sites. Community structure had low similarity (20-26%) and the environmental factors showed a weak contribution to the distribution pattern observed. Despite this, the light availability at the stream-bed seems to be a major influence on the macroalgal seasonal dynamics. We suggest that macroalgae communities are predominantly composed of rare species, and this could explain the lack of a clear spatial and temporal variation pattern of these organisms.


A distribuição espacial e temporal das macroalgas lóticas em riachos do sudeste do Brasil foram avaliadas por um ano. As flutuações na composição de espécies de macroalgas e fatores ambientais foram monitorados mensalmente. A região apresenta um clima tropical, com estações chuvosas e secas definidas. Dezenove espécies foram encontradas, com predomínio de Chlorophyta (52,7% das espécies), seguido por Cianobactérias (26,3%), Ochrophyta e Rhodophyta (10,5% cada). Scytonema arcangeli teve o maior número de registros (63,6%), enquanto Mougeotia capucina ocorreu em todos os pontos de amostragem. A estrutura da comunidade teve baixa similaridade (20-26%) e os fatores ambientais mostraram uma fraca contribuição para o padrão de distribuição observado. Apesar disso, a disponibilidade de luz no leito do riacho parece ser de grande influência sobre a dinâmica sazonal de macroalgas. Nós sugerimos que as comunidades de macroalgas são predominantemente compostas por espécies raras, e isso poderia explicar a falta de um padrão claro de variação espacial e temporal desses organismos.

5.
Integr Biol (Camb) ; 6(11): 1088-99, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25212181

RESUMO

The bacterial two-component system (TCS) regulates genes that are crucial for virulence in several pathogens. One of such TCS, the PhoPR system, consisting of a transmembrane sensory histidine kinase protein (PhoR) and an intracellular response regulator protein (PhoP), has been reported to have a major role in mycobacterial pathogenesis. We knocked out the phoP in C. pseudotuberculosis, the causal organism of caseous lymphadenitis (CLA), and using a combination of in vitro and in vivo mouse system, we showed for the first time, that the PhoP of C. pseudotuberculosis plays an important role in the virulence and pathogenicity of this bacterium. Furthermore, we modeled the PhoP of C. pseudotuberculosis and our docking results showed that several natural compounds including Rhein, an anthraquinone from Rheum undulatum, and some drug-like molecules may target PhoP to inhibit the TCS of C. pseudotuberculosis, and therefore may facilitate a remarkable attenuation of bacterial pathogenicity being the CLA. Experiments are currently underway to validate these in silico docking results.


Assuntos
Proteínas de Bactérias/imunologia , Infecções por Corynebacterium/imunologia , Corynebacterium pseudotuberculosis/patogenicidade , Transdução de Sinais/imunologia , Animais , Antraquinonas/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/genética , Bioensaio , Linhagem Celular , Sobrevivência Celular/imunologia , Infecções por Corynebacterium/genética , Corynebacterium pseudotuberculosis/genética , Corynebacterium pseudotuberculosis/imunologia , DNA Bacteriano/química , DNA Bacteriano/genética , Macrófagos , Camundongos , Camundongos Endogâmicos BALB C , Simulação de Acoplamento Molecular , Reação em Cadeia da Polimerase , Deleção de Sequência/genética , Deleção de Sequência/imunologia , Virulência
6.
Aust Endod J ; 34(1): 19-24, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18352899

RESUMO

The aim of this study was to evaluate the antimicrobial capacity of sodium hypochlorite (1% and 5%) and chlorhexidine (0.12%, 0.5% and 1%) with or without the addition of organic material (bovine serum albumin, BSA) against some bacterial samples (Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Porphyromonas gingivalis and Fusobacterium nucleatum) using two activity tests (contact and diffusion agar tests). In the contact test (first model), bacterial samples were kept in contact with each irrigating solution for different time intervals: immediately (t(0)), 5 min (t(5)), 15 min (t(15)) and 30 min (t(30)). The agar diffusion test was the second model used. In half the specimens, 0.5% BSA was added to simulate organic tissue present in the root canal. Bacterial growth was evaluated for each microorganism and activity test. Each test was repeated 10 times. In the contact test, 0.12% chlorhexidine solution (CHX) did not eliminate E. faecalis at any tested time. CHX at 0.5% eliminated all strains except E. faecalis after immediate contact. All strains were eliminated by 1% CHX, 1% NaOCl and 5% NaOCl. BSA did not interfere with the antimicrobial activity of the irrigating solutions. In the agar diffusion test, all solutions exhibited zones of antimicrobial activity; however, BSA interfered with the antimicrobial activity of NaOCl and CHX. Under the condition of the contact test, the 0.12% CHX was ineffective in eliminating E. faecalis, while 0.5% CHX, 1% CHX, 1% NaOCl and 5% NaOCl showed antibacterial effectiveness against all the tested bacterial strains. The addition of an organic load interfered with the accuracy of the agar diffusion test.


Assuntos
Bactérias Anaeróbias/efeitos dos fármacos , Clorexidina/farmacologia , Irrigantes do Canal Radicular/farmacologia , Hipoclorito de Sódio/farmacologia , Clorexidina/administração & dosagem , Relação Dose-Resposta a Droga , Enterococcus faecalis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Fusobacterium nucleatum/efeitos dos fármacos , Imunodifusão , Testes de Sensibilidade Microbiana , Porphyromonas gingivalis/efeitos dos fármacos , Irrigantes do Canal Radicular/administração & dosagem , Soroalbumina Bovina/farmacologia , Hipoclorito de Sódio/administração & dosagem , Staphylococcus aureus/efeitos dos fármacos
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