The Individual and Combined Neurotoxic Effects of Cyanobacterial Toxins

................................................................................................................................................38 INTRODUCTION ..........................................................................................................................................39 MATERIALS AND METHODS........................................................................................................................42 RESULTS ....................................................................................................................................................50 DISCUSSION ...............................................................................................................................................55 ACKNOWLEDGEMENTS ..............................................................................................................................57 3. MANUSCRIPT II...............................................................................................................................58 ABSTRACT .................................................................................................................................................58 INTRODUCTION ..........................................................................................................................................59 MATERIALS AND METHODS........................................................................................................................61 RESULTS ....................................................................................................................................................66 DISCUSSION ...............................................................................................................................................71 CONCLUSION .............................................................................................................................................73 ACKNOWLEDGEMENTS ..............................................................................................................................73................................................................................................................................................58 INTRODUCTION ..........................................................................................................................................59 MATERIALS AND METHODS........................................................................................................................61 RESULTS ....................................................................................................................................................66 DISCUSSION ...............................................................................................................................................71 CONCLUSION .............................................................................................................................................73 ACKNOWLEDGEMENTS ..............................................................................................................................73 4. MANUSCRIPT III .............................................................................................................................74 ABSTRACT .................................................................................................................................................74 INTRODUCTION ..........................................................................................................................................75 MATERIALS AND METHODS........................................................................................................................76 RESULTS ....................................................................................................................................................80 DISCUSSION ...............................................................................................................................................89 ACKNOWLEDGEMENTS ..............................................................................................................................92................................................................................................................................................74 INTRODUCTION ..........................................................................................................................................75 MATERIALS AND METHODS........................................................................................................................76 RESULTS ....................................................................................................................................................80 DISCUSSION ...............................................................................................................................................89 ACKNOWLEDGEMENTS ..............................................................................................................................92 5. ADDITIONAL DATA........................................................................................................................93 5.1. MC IN VIVO STUDY.......................................................................................................................93 5.2. PRELIMINARY RESULTS AND DISCUSSION ....................................................................................96 6. OVERALL DISCUSSION...............................................................................................................100 6.1. TOXIC CYANOBACTERIA: A GROWING RISK?..............................................................................100 6.2. MICROCYSTINS – POTENT NEUROTOXINS? .................................................................................101 6.3. INVOLVEMENT OF ORGANIC ANION TRANSPORTING POLYPEPTIDES IN MICROCYSTIN UPTAKE ...103 6.4. MICROCYSTIN CONGENER-DEPENDENT AND NEURON-SPECIFIC TOXICITY .................................105 6.5. ASSESSMENT OF HUMAN HEALTH RISK, ARISING FROM MICROCYSTIN CONGENER DIFFERENCES AND THEIR NEUROTOXIC POTENTIAL .........................................................................................106 6.6. CONCLUSIONS AND FUTURE PERSPECTIVES ...............................................................................107 7. REFERENCES.................................................................................................................................109