Peaceful use of disastrous neurotoxicants.

The increasing exposure to environmental neurotoxicants in the last decades caused serious health problems in the world population. Some of the neurotoxic agents are being used in agriculture and household such as insecticides and rodenticides and others are of natural origin like snake and scorpion venoms. Additional group of harmful substances is the chemical warfare agents including nerve and blistering agents that are known for their disastrous effects on neuronal tissues. The present paper presents a combination of epidemiological/clinical and molecular approaches for investigating the effect of certain groups of neurotoxicants on a variety of pathologies. The work of Finkelstein and coworkers describes epidemiological and clinical studies on acute and chronic organophosphate (OP)-induced neurotoxicity in certain populations in Israel. They mainly investigated the neurotoxic effects of low-level long-term exposure to OP in agricultural areas but also dealt with acute exposures as well. A molecular approach to OP mechanism of neuronal injury was described by Milatovic and coworkers. They demonstrated OP-induced oxidative injury in pyramidal neurons in the CA1 hippocampal area and its suppression by antioxidants. Lecht and coworkers described the novel snake venom angioneurins as important mediators of the physiological cross-talk between the cardiovascular and nervous systems. They also showed that under certain conditions these angioneurins may induce pathologies such as tumor development or disruption of the vascular barrier function during envenomation. Additional mechanistic/therapeutic approach was presented by Brodsky, Rosengarten, Proscura, Shapira and Wormser. They developed a novel anti-inflammatory peptide that reduced skin irritation induced by heat and sulfur mustard (SM) stimuli. Since SM causes neuropsychiatric symptoms and alterations in neurological functions this peptide may serve as a potential treatment of neuronal injuries caused by environmental neurotoxicants. These reviews highlight different aspects of neurotoxicity, addressing epidemiology and mechanisms of toxicity; and identifying novel potential therapies.

Currents contributing to decision making in neurons B31/B32 of Aplysia.

Biophysical properties of neurons contributing to the ability of an animal to decide whether or not to respond were examined. B31/B32, two pairs of bilaterally symmetrical Aplysia neurons, are major participants in deciding to initiate a buccal motor program, the neural correlate of a consummatory feeding response. B31/B32 respond to an adequate stimulus after a delay, during which time additional stimuli influence the decision to respond. B31/B32 then respond with a ramp depolarization followed by a sustained soma depolarization and axon spiking that is the expression of a commitment to respond to food. Four currents contributing to decision making in B31/B32 were characterized, and their functional effects were determined, in current- and voltage-clamp experiments and with simulations. Inward currents arising from slow muscarinic transmission were characterized. These currents contribute to the B31/B32 depolarization. Their slow activation kinetics contribute to the delay preceding B31/B32 activity. After the delay, inward currents affect B31/B32 in the context of two endogenous inactivating outward currents: a delayed rectifier K+ current (I(K-V)) and an A-type K+ current (I(K-A)), as well as a high-threshold noninactivating outward current (I(maintained)). Hodgkin-Huxley kinetic analyses were performed on the outward currents. Simulations using equations from these analyses showed that I(K-V) and I(K-A) slow the ramp depolarization preceding the sustained depolarization. The three outward currents contribute to braking the B31/B32 depolarization and keeping the sustained depolarization at a constant voltage. The currents identified are sufficient to explain the properties of B31/B32 that play a role in generating the decision to feed.