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1.
Toxicology ; 387: 67-80, 2017 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-28627408

RESUMO

We have previously demonstrated that maternal exposure to glyphosate-based herbicide (GBH) leads to glutamate excitotoxicity in 15-day-old rat hippocampus. The present study was conducted in order to investigate the effects of subchronic exposure to GBH on some neurochemical and behavioral parameters in immature and adult offspring. Rats were exposed to 1% GBH in drinking water (corresponding to 0.36% of glyphosate) from gestational day 5 until postnatal day (PND)-15 or PND60. Results showed that GBH exposure during both prenatal and postnatal periods causes oxidative stress, affects cholinergic and glutamatergic neurotransmission in offspring hippocampus from immature and adult rats. The subchronic exposure to the pesticide decreased L-[14C]-glutamate uptake and increased 45Ca2+ influx in 60-day-old rat hippocampus, suggesting a persistent glutamate excitotoxicity from developmental period (PND15) to adulthood (PND60). Moreover, GBH exposure alters the serum levels of the astrocytic protein S100B. The effects of GBH exposure were associated with oxidative stress and depressive-like behavior in offspring on PND60, as demonstrated by the prolonged immobility time and decreased time of climbing observed in forced swimming test. The mechanisms underlying the GBH-induced neurotoxicity involve the NMDA receptor activation, impairment of cholinergic transmission, astrocyte dysfunction, ERK1/2 overactivation, decreased p65 NF-κB phosphorylation, which are associated with oxidative stress and glutamate excitotoxicity. These neurochemical events may contribute, at least in part, to the depressive-like behavior observed in adult offspring.


Assuntos
Comportamento Animal/efeitos dos fármacos , Depressão/induzido quimicamente , Ácido Glutâmico/metabolismo , Glicina/análogos & derivados , Herbicidas/toxicidade , Hipocampo/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Estresse Oxidativo/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Acetilcolinesterase/metabolismo , Fatores Etários , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Sítios de Ligação , Fibras Colinérgicas/efeitos dos fármacos , Fibras Colinérgicas/metabolismo , Depressão/metabolismo , Depressão/fisiopatologia , Depressão/psicologia , Feminino , Proteínas Ligadas por GPI/metabolismo , Idade Gestacional , Ácido Glutâmico/química , Glicina/química , Glicina/metabolismo , Glicina/toxicidade , Herbicidas/química , Herbicidas/metabolismo , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Simulação de Acoplamento Molecular , Estrutura Molecular , Atividade Motora/efeitos dos fármacos , NF-kappa B/metabolismo , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/fisiopatologia , Síndromes Neurotóxicas/psicologia , Gravidez , Ligação Proteica , Ratos Wistar , Receptores de N-Metil-D-Aspartato/agonistas , Receptores de N-Metil-D-Aspartato/metabolismo , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo , Relação Estrutura-Atividade , Transmissão Sináptica/efeitos dos fármacos , Glifosato
2.
Sci Rep ; 7: 46486, 2017 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-28429758

RESUMO

Intracellular lipid binding proteins (iLBPs) play a role in the transport and cellular uptake of fatty acids and gene expression regulation. The aim of this work was to characterize the iLBP gene family of the Pacific oyster Crassostrea gigas, one of the most cultivated marine bivalves in the world, using bioinformatics and molecular biology approaches. A total of 26 different iLBPs transcripts were identified in the Pacific oyster genome, including alternative splicing and gene duplication events. The oyster iLBP gene family seems to be more expanded than in other invertebrates. Furthermore, 3D structural modeling and molecular docking analysis mapped the main amino acids involved in ligand interactions, and comparisons to available protein structures from vertebrate families revealed new binding cavities. Ten different CgiLBPs were analyzed by quantitative PCR in various tissues of C. gigas, which suggested differential prevalent gene expression of CgiLBPs among tissue groups. The data indicate a wider repertoire of iLBPs in labial palps, a food-sorting tissue. The different gene transcription profiles and reported docking systems suggest that the iLBPs are a non-generalist ligand binding protein family with specific functions.


Assuntos
Processamento Alternativo , Proteínas de Transporte , Crassostrea , Duplicação Gênica , Simulação de Acoplamento Molecular , Família Multigênica , Animais , Proteínas de Transporte/biossíntese , Proteínas de Transporte/química , Proteínas de Transporte/genética , Crassostrea/química , Crassostrea/genética , Crassostrea/metabolismo , Metabolismo dos Lipídeos/fisiologia
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