23. PROBING THE ROLE OF THE ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR IN PSYCHOSIS

摘要

There is growing support for aberrant nicotinic, cholinergic signaling in psychosis. Converging evidence links altered activity of the cerebral alpha7 nicotinic acetylcholine receptor (α7-nAChR) to psychotic symptoms as well as cognitive deficits observed in individuals with psychosis. While recent evaluations of agonist medications targeting the α7-nAChR for cognitive improvement have not resulted in robust outcomes, our understanding of this receptor and its function in health and disease is informing new, promising, therapeutic approaches that target the α7-nAChR. This symposium will bring together scientists from across the nation who are probing the role of the α7-nAChR in neural circuits relevant to psychosis using preclinical, animal model, and clinical research approaches. We will present new findings that support the role of the α7-nAChR in schizophrenia and we will discuss how these findings may guide future advances in therapeutic or preventative interventions. We include four speakers on our panel:1. Philip Haydon, Ph.D. (Tufts University) will present in vitro and in vivo work suggesting that NMDA receptor hypofunction in schizophrenia may be related to diminished activity of the α7-nAChR that is expressed on astrocytes in the hippocampus. His findings may guide strategies for using medications that stimulate the α7-nAChR to normalize NMDA receptor function in schizophrenia.2. Anthony A. Grace, Ph.D. (University of Pittsburgh) will present data from animal studies that support aberrant activity of the α7-nAChR, as well as the ability of novel classes of α7-nAChR-modulating drugs acting in the hippocampus to reverse the hyperdopaminergic tone observed in a developmental disruption model of schizophrenia.3. Sharon Hunter, Ph.D. (University of Colorado) will present data from recent clinical research probing preventative pharmacologic strategies targeting cholinergic signaling in psychosis. Specifically, she will present findings from study of the cerebral evoked response to repeated auditory stimuli in pregnant women and their newborns after perinatal phosphatidylcholine supplementation. 4. Jennifer M. Coughlin, M.D. (Johns Hopkins University) will present in vivo imaging findings using [18F]ASEM PET in patients with recent onset of psychosis. These data support the hypothesized low availability of the α7-nAChR in the hippocampus of non-smoker patients with recent onset of psychosis, particularly those with non-affective psychosis.The discussant will be Akira Sawa, M.D., Ph.D. (Johns Hopkins Univesity). Dr. Sawa has expertise in translational research in schizophrenia and will discuss how these findings may guide future research approaches to study aberrant cholinergic signaling and related therapeutic opportunities in psychosis.