Development of bioassays for natural products neurotoxicity evaluation in rodents' central nervous system

Abstract

The neurotoxical secretions of many arthropods are composed of peptides, acylpolyamines and alkaloids which present pharmacological effects in a number of systems, including the nervous system. The chemical compounds of this secretions have neurological actions, being used in the prey capture and against predators. This occur because these neurotoxins affect the synaptic transmissions and the functioning of ionic channel, further the despolarization of the muscle fibers and/or nervous terminations. Since the beggining of eighties the non-proteic/peptidic compounds presenting molecular masses have attracted a lot of attention both due to the academic importance and in applied researches. Compounds such as acylpolyamines, nucleosides-toxins, b-carbolines and dyazenylaryl organometallic have been characterized in the last years from toxic secretions of spider and wasps. There is a crescent necessity for investigating their actions in biological systems in order to justify their properties as bioinsectides, model-drugs for development of new pharmaceuticals and even as tools in Neuroscience studies.The Bioprospecta Program will provide a lot of novel natural products, derivated from animals, plants and microorganims, present in the biodiversity of Sao Paulo State. Toxic compounds from Arthropod and other organisms might be discovered in order to develop specific assays capable to be used within Bioprospecta network.The low molecular mass compounds isolated from spiders and social wasps will be administrated either intracerebroventricularly or endovenously in Wistars rats. Their biological actions will be mapped in the central nervous system (CNS) by using the technique of Fos expression. Fos protein is a inducible transcription factor, whose activation is a sensible tool for mapping different pharmacological, eletric and physiological stimulus in neurons activated. Such compounds will enhance nucleus of cells after immunohistochemical assays, indicating the action of the neurotoxins in the CNS of rats. Neurons with Fos expression will be characterized by dual label (fos/tirosine hidroxilase, fos/NMR1, fos/rGlu2/3, fos/orexine, fos/5HT2A or by in situ hybridization (GAD-67). The final set-up of this bioassay will be available to the all groups of Bioprospecta network. (AU)