Microcystin-LR induces changes in the GABA neurotransmitter system of zebrafish

It has been reported that exposure to microcystins altered adult zebrafish swimming performance parameters, but the possible mechanisms of action remain unknown. Neuronal activity depends on the balance between the number of excitatory and inhibitory processes which are associated with neurotransmitters. In the present study, zebrafish embryos (5 d post-fertilization) were exposed to 0, 0.3, 3 and 30 μg/L (microcystin-LR) MCLR for 90 day until reaching sexual maturity. To investigate the effects of MCLR on the neurotransmitter system, mRNA levels involved in amino acid g-aminobutyric acid (GABA) and glutamate metabolic pathways were tested using quantitative real-time PCR. Significant increase of GABAA receptor, alpha 1 (gabra1), glutamate decarboxylase (gad1b), glutaminase (glsa) and reduction of mRNA expression of GABA transporter (gat1) at transcriptional level were observed in the brain. Meanwhile, western blotting showed that the protein levels of gabra1, gad1b were induced by MCLR, whereas the expression of gat1 was decreased. In addition, MCLR induced severe damage to cerebrum ultrastructure, showing edematous and collapsed myelinated nerve fibers, distention of endoplasmic reticulum and swelling mitochondria. Our results suggested that MCLR showed neurotoxicity in zebrafish which might attribute to the disorder of GABA neurotransmitter pathway.