Study of the manganese effects on the nervous system of a vertebrate model, thezebrafish (Danio rer

Abstract

Manganese (Mn) is an essential trace metal required for humans, being its homeostasis necessary to prevent its toxicity. It is known that Mn overexposure causes its accumulation in the brain, resulting in neurological disorders, motor disturbances and behavioural impairment, among others. To study synaptic/neuronal injury generated by chronic chemical exposure, the synaptic protein neurogranin is analysed. Due to its levels being altered in the brain of patients with neurological disease or disorders, it is considered a promising biomarker of neurodegeneration. Despite its relevance, neurogranin distribution in the nervous system has not been characterized in zebrafish (Danio rerio, Teleostei). This dissertation focuses on the study of the effects that manganese overexposure produces on neurogranin expression, as well as on the larval phenotype and behaviour in zebrafish. Neurogranin distribution in the adult brain and during development was characterized here. Compared to control individuals, zebrafish larvae overexposed to manganese showed a reduction both in neurogranin immunofluorescence intensity in the brain and in mRNA expression of neurogranincoding genes (nrgna and nrgnb) in whole larvae, in addition to other phenotypic differences. Moreover, embryos exposed to high concentrations of manganese showed behavioural alterations, such as postural defects, reduced motor output and light preference, but no differences in optomotor response were observed.