Cellular and molecular mechanisms involved in the role of atypical neurotransmitters in neuropsychiatric disorders

Abstract

In the last 15 years our group has contributed to a better understanding of the role of nitric oxide (NO) and endocannabinoids (eCBs) in physiological and pathophysiological processes of the central nervous system. We showed that manipulations of these atypical neurotransmitters are able to change behavioral and autonomic responses of laboratory animals submitted to animal models of anxiety, depression, psychosis and motor disorders. We have also shown that the phytocannabinoid cannabidiol (CBD), which, among other mechanisms, can act on eCB-mediated neurotransmission, modifies these same responses in animals and humans. The main goal of the present project, besides allowing for the continuation of this research line by approaching unresolved questions regarding NO, eCBs and CBD effects (such as unexplored sites of action, possible antiagressive and antiparkinsonin effects of CBD), is to elucidate the cellular (neuroplastic and immunological changes) and molecular (signaling pathways) mechanisms responsible for these effects. To this aim the project will try to integrate distinct methodological approaches, varying from behavioral and autonomic evaluation to measurements of gene expression, neuronal activity in specific neuronal groups, epigenetic changes, and gene silencing. As a result, in addition to increase our knowledge about these systems and the mechanisms of CBD, the Project will permit the incorporation of new and important methodological approaches to our research group. By incorporating a significant number of post-graduate students and post-docs, it will also facilitate the formation of new researchers in Neuroscience and Pharmacology. (AU)