Project Summary

Maria Cecilia Angulo, Ph.D. (Young Investigator 2005) of ESPCI-Ecole Superieure de Physique et Chemie Industrielles de la Ville de Paris, hopes to study the role of nicotinic acetylcholine receptors (nACHR) and monoamine oxidase B (MAO-B) in astrocytes and their possible role in schizophrenia and smoking. Astrocytes are a type of glial cell, which are numerous, non-neuronal structural cells in the brain that interact with neurons. Astrocytes express nACHRs—a mutation in which has been linked to schizophrenia—that lead to intracellular calcium ion increases in cell culture. These calcium ion increases elicit the release of gliotransmitters, such as glutamate and ATP, onto neurons, inducing synaptic activity changes. Glial nAChRs are therefore good candidates for regulating “gliotransmission.” Glial MAO-Bs also are implicated in the effects of tobacco. Dr. Angulo hypothesizes that a reduction in MAO-B activity may synergize with nicotine to produce smoking behavioral effects. Many schizophrenics smoke. The study’s goal is to understand the synergistic effect of glial nAChR activity and MAO-B inhibition in modulating synaptic neurotransmission. First, the researchers will characterize nAChR subunits preferentially expressed by astrocytes. Second, they will characterize the influence of both glial nAChRs and MAO-B inhibitors in neuronal plasticity using genetically engineered mice in which nAChRs have been disrupted. This project should tease apart the functioning of the cholinergic system and its role in schizophrenia and tobacco addiction.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia\Nicotine

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