Antidepressant fluoxetine suppresses neuronal growth from both vertebrate and invertebrate neurons and perturbs synapse formation betweenLymnaeaneurons

Autor:	Maria P. Richard, Jan van Minnen, Svetlana Farkas, Collin C. Luk, Fenglian Xu, Angela M. Getz, Wali Zaidi, Arthur J. Lee, Naweed I. Syed
Rok vydání:	2010
Předmět:	Neurite Growth Cones Biology Neurotransmission Serotonergic Synaptic Transmission Calcium imaging Postsynaptic potential Cellular neuroscience Fluoxetine Neurites Animals Growth cone Cells Cultured Lymnaea Cerebral Cortex Neurons Microscopy Confocal Dose-Response Relationship Drug General Neuroscience Neural Inhibition Actins Rats Culture Media Conditioned Antidepressive Agents Second-Generation Antidepressant Calcium Neuroscience
Zdroj:	European Journal of Neuroscience. 31:994-1005
ISSN:	1460-9568 0953-816X
Popis:	Current treatment regimes for a variety of mental disorders involve various selective serotonin reuptake inhibitors such as Fluoxetine (Prozac). Although these drugs may 'manage' the patient better, there has not been a significant change in the treatment paradigm over the years and neither have the outcomes improved. There is also considerable debate as to the effectiveness of various selective serotonin reuptake inhibitors and their potential side-effects on neuronal architecture and function. In this study, using mammalian cortical neurons, a dorsal root ganglia cell line (F11 cells) and identified Lymnaea stagnalis neurons, we provide the first direct and unequivocal evidence that clinically relevant concentrations of Fluoxetine induce growth cone collapse and neurite retraction of both serotonergic and non-serotonergic neurons alike in a dose-dependent manner. Using intracellular recordings and calcium imaging techniques, we further demonstrate that the mechanism underlying Fluoxetine-induced effects on neurite retraction from Lymnaea neurons may involve lowering of intracellular calcium and a subsequent retardation of growth cone cytoskeleton. Using soma-soma synapses between identified presynaptic and postsynaptic Lymnaea neurons, we provide further direct evidence that clinically used concentrations of Fluoxetine also block synaptic transmission and synapse formation between cholinergic neurons. Our study raises alarms over potentially devastating side-effects of this antidepressant drug on neurite outgrowth and synapse formation in a developing/regenerating brain. Our data also demonstrate that drugs such as Fluoxetine may not just affect communication between serotonergic neurons but that the detrimental effects are widespread and involve neurons of various phenotypes from both vertebrate and invertebrate species.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fda5fad44545729558066aecbc4cd6cd https://doi.org/10.1111/j.1460-9568.2010.07129.x Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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