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b-Carbolines are potential endogenous and exogenous neurotoxicants that may contribute to the pathogenesis of Parkinson's disease. The 2,9-dimethyl-b-carbolinium ion (either 2,9-dimethyl-b-norharmanium or 2,9-Me 2 NH + ) was found to be neurotoxic in primary mesencephalic cultures and to be a potent inhibitor of mitochondrial complex I. However, the precise mechanisms of cell death remained obscure. Here, we investigated the mechanism of cell death in primary dopaminergic cultures of the mouse mesencephalon mediated by 2,9-Me 2 NH + . The b-carboline caused preferential death of dopaminergic neurones, which could not be attributed to cellular uptake via the dopamine transporter. Transient incubation with 2,9-Me 2 NH + for 48 h caused a progressive deterioration in the morphology of dopaminergic neurones during a 5-day recovery period and persistent damage to the overall culture. An increase in free radical production and caspase-3 activity, as well as a decrease of respiratory activity, mitochondrial membrane potential and ATP content, contributed to toxicity and pointed to an apoptotic mode of cell death, although a significant quantity of cells dying via necrosis were present simultaneously. These data underline the preferential susceptibility of dopaminergic neurones to 2,9-Me 2 NH + as a potent, oxidative stress generating neurotoxin. Keywords: apoptosis, b-carboline, 2,9-Me 2 NH + , dopaminergic neurones, necrosis, oxidative stress. The meperidine analogue MPTP (Fig. 1) has long been known to be toxic for dopaminergic neurones and to cause features that are found in Parkinson's disease (PD) (Langston et al. 1983;Mytilineou and Cohen 1984). Structural analogues of MPTP with a nitrogen bridge are the b-carbolines (BCs, Fig. 1), which are heterocyclic indole alkaloids that occur ubiquitously in our environment and diets, but are also formed endogenously in the human body. They can be found in grilled meat, alcoholic beverages and brewed coffee, but are also found in medicinal plants like Peganum harmala and in significant quantities in tobacco smoke (Sugimura and Nagao 1979;Bosin and Faull 1988;Rommelspacher et al. 1994;Herraiz 2002;Pfau and Skog 2004;Herraiz and Chaparro 2005). Furthermore, BCs have been isolated from human body fluids and tissues, e.g. blood platelets, milk, urine, brain, liver, kidney and lens (Honecker et al. 1980;Boeira et al. 2001).BCs are metabolized via sequential di-N-methylation to bioactive 2,9-di-N-methylated carbolinium cations (Collins et al. 1992) Address correspondence and reprint requests to Dr Gabriele Gille, Department of Neurology, Technical University of Dresden, Fetscherstr. 74, 01307 Dresden, Germany. E-mail: Gabriele.Gille@neuro.med.tu-dresden.deAbbreviations used: BC, b-carboline; CM-H2DCFDA, fluorescent indicator 5-(and-6)-chloromethyl-2¢,7¢-dichlorodihydrofluorescein diacetate acetyl ester; DAF-FM diacetate, nitric oxide indicator 4-amino-5-methylamino-2¢,7¢-difluorescein diacetate; DAT, dopamine transporter; DIV, days in vitro; DMEM, Dulbecco's modified Eag...

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Interactions between mysids and invertebrates other than pelagic zooplankton have not been well studied. We tested the hypothesis that the mysid Tenagomysis chiltoni preys on the co-occurring amphipod Paracalliope fluviatilis in laboratory experiments. In prey size preference experiments with single prey species, male and female T. chiltoni consumed more small than large amphipods in the absence of the macrophyte Elodea canadensis, but were not selective when macrophytes were present. When offered small and large Daphnia, T. chiltoni males consumed more small than large Daphnia, whereas female T. chiltoni did not show any preference. When amphipods and Daphnia of similar size were presented together, male T. chiltoni strongly selected Daphnia in the presence and absence of E. canadensis, whereas female mysids did so only in the presence of macrophytes. The total number of prey consumed by each sex did not differ between macrophyte treatments. However, female T. chiltoni, which are larger than males, consumed more prey than males. These data suggest that mysids may be an important source of mortality to the amphipod P. fluviatilis. Mysids may also prey on amphipods in other aquatic systems where they co-occur.