Biophysical Society Thematic Meeting| Padova 2019

Quantitative Aspects of Membrane Fusion and Fission

Poster Abstracts

53-POS Board 53 ABNORMALLY INCREASED AMOUNT AND VELOCITY OF EXTRASYNAPTIC SECRETION IN OLFACTORY NEURONAL PRECURSORS FROM PATIENTS WITH SCHIZOPHRENIA OR BIPOLAR DISEASE Montserrat G Cercós 1 ; Citlali Trueta 1 ; Gloria Benítez-King 2 ; 1 Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Neurophysiology, Mexico City, Distrito Federal, Mexico 2 Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Neuropharmacology, Mexico City, Distrito Federal, Mexico The alterations that underlie the pathophysiology of neuropsychiatric disorders include the dysregulation of structural and functional properties of neurons. Among these, the secretion of neurotransmitters and hormones, which plays a key role for neuronal communication and development, is altered. Neuronal precursors from the human olfactory epithelium have been recently characterized as a reliable model for studying the etiopathogenesis of neuropsychiatric disorders. Our previous work has shown that melatonin enhances the development of morphological and functional features of cloned olfactory neuronal precursors (ONPs) from a healthy subject. Here we studied extrasynaptic secretion in primary cultures of ONPs obtained one patient with disorganized schizophrenia, one with paranoid schizophrenia and one with bipolar disorder. Secretion was evaluated from the cumulative changes of FM1-43 fluorescence in response to depolarization. Potassium-evoked secretion from the soma and axons of ONPs obtained from schizophrenia or bipolar patients had an increased amplitude and velocity, when compared with ONPs from age- and gender-matched healthy control subjects (HCS). This suggests the fusion of larger amounts of vesicles, which rested closer or were mobilized faster to the plasma membrane. As a first approach to study the alterations underlying this increase in secretion, we measured the thickness of microfilaments stained with rhodamine-phalloidin. The actin microfilament bundles of ONPs from patients were significantly thicker than those of HCS. Interestingly, treatment for 12 h with melatonin modulated the abnormally increased secretion in ONPs from schizophrenia and bipolar patients and brought it to levels similar to those found in HCS ONPs. Melatonin also induced the thickening of actin microfilament bundles. Our results suggest that cytoskeletal modifications change vesicle mobilization to the membrane, thus producing alterations in neurotransmitter systems observed in neuropsychiatric disorders.

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