RESUMEN
The present study provides in vivo evidence to prove the functional plasticity of monocarboxylate transporters (MCTs) in brains of vertebrates using zebrafish (Danio rerio) as a model. In the mammalian central nervous system (CNS), energy demands are largely met by oxidation of glucose. In recent studies, in addition to glucose, lactate is also considered an energy substrate for the CNS. Astrocytes were demonstrated to play an important role in transporting lactate as metabolic substrate from capillaries to neurons through monocarboxylate transporters (MCTs). The present study was to use zebrafish as an in vivo model to test the hypothesis of whether the various MCT homologs play differential roles in the development and functioning of the CNS. Using RT-PCR and double in situ hybridization coupling with immunocytochemical staining experiments, zebrafish MCTs1-4 were all found to be expressed in brains of embryos, and were further elucidated to be localized in both neurons and astrocytes. Loss-of-functions by morpholino knockdown further provided in vivo evidences to infer that zMCTs1, -2, and -4 may be involved in metabolite transport and functioning in the developing brain. Subsequent rescue experiments with capped mRNAs of specific isoforms further indicated that zMCT2 is an indispensable monocarboxylate-transporting route for CNS development and function in zebrafish. This information is essential for identifying proper candidates of MCT isoforms that are involved in the development and functioning of the CNS.
Asunto(s)
Encéfalo/metabolismo , Proteínas de Peces/genética , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Transportadores de Ácidos Monocarboxílicos/genética , Proteínas de Pez Cebra/genética , Pez Cebra/genética , Secuencia de Aminoácidos , Animales , Astrocitos/metabolismo , Encéfalo/embriología , Encéfalo/crecimiento & desarrollo , Embrión no Mamífero/citología , Embrión no Mamífero/embriología , Embrión no Mamífero/metabolismo , Proteínas de Peces/metabolismo , Técnicas de Silenciamiento del Gen , Inmunohistoquímica , Hibridación in Situ , Datos de Secuencia Molecular , Transportadores de Ácidos Monocarboxílicos/metabolismo , Neuronas/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Aminoácido , Factores de Tiempo , Pez Cebra/embriología , Pez Cebra/crecimiento & desarrollo , Proteínas de Pez Cebra/metabolismoRESUMEN
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