Zebrafish as model organism in a study on the neurodegeneration

Cadmium is a heavy metal increasingly widespread in the environment that is associated with neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. In the present work we analyzed the levels of accumulation of β-amyloid peptide and glutamate dehydrogenase in Zebrafish brain in order to verify possible alterations. β-amyloid peptide is between the major players in the pathology of Alzheimer's disease according to the amyloid cascade hypothesis; glutamate dehydrogenase is an important enzyme for many metabolic processes and for the functionality of neurotransmission. Adult specimens of Zebrafish were exposed for 16 days to 1.0 mg/l of CdCl2 and the brains were analyzed after 2, 7 and 16 days of exposure. By Western blotting experiments we have shown that the levels of β-amyloid peptide and glutamate dehydrogenase increased in a progressive manner in the course of treatment. In particular it has been found an increase in the levels of glutamate dehydrogenase of 2.5 times after 16 days, while for the β-amyloid peptide has been possible to observe a significant increase of its accumulation already after two days of exposure to the metal with a final increase of 4-fold major. By immunohistochemical analysis we verified the increase in signal intensity in the treated animals both for the β-amyloid peptide and for glutamate dehydrogenase. The first signal was in particular increased in the medulla oblongata, in the dorsal and the ventral telencephalon and at the level of the cerebellum in the area of Purkinje neurons; glutamate dehydrogenase was more immunorevealed in the hypothalamic area of diencephalon, in the area of Purkinje cells of cerebellum and in optic tectum and telencephalon. Our results confirm the toxic action performed by cadmium in the brain, highlighting in particular the effects on nerve cells. The data show a correlation between cadmium and alteration of the metabolism of β-amyloid peptide also in Zebrafish brain. In addition, the variation observed for glutamate dehydrogenase could attest an alteration in the metabolism of excitatory and inhibitory neurotransmitters, another characteristic of neurodegenerative diseases. Moreover these results validate zebrafish as a good experimental model in the studies on neurodegenerative diseases associated to heavy metals as cadmium.