title: Fluoxetine induces proliferation and inhibits differentiation of hypothalamic neuroprogenitor cells in vitro.
abstract: A significant number of children undergo maternal exposure to antidepressants and they often present low birth weight. Therefore, it is important to understand how selective serotonin reuptake inhibitors (SSRIs) affect the development of the hypothalamus, the key center for metabolism regulation. In this study we investigated the proliferative actions of fluoxetine in fetal hypothalamic neuroprogenitor cells and demonstrate that fluoxetine induces the proliferation of these cells, as shown by increased neurospheres size and number of proliferative cells (Ki-67+ cells). Moreover, fluoxetine inhibits the differentiation of hypothalamic neuroprogenitor cells, as demonstrated by decreased number of mature neurons (Neu-N+ cells) and increased number of undifferentiated cells (SOX-2+ cells). Additionally, fluoxetine-induced proliferation and maintenance of hypothalamic neuroprogenitor cells leads to changes in the mRNA levels of appetite regulator neuropeptides, including Neuropeptide Y (NPY) and Cocaine-and-Amphetamine-Regulated-Transcript (CART). This study provides the first evidence that SSRIs affect the development of hypothalamic neuroprogenitor cells in vitro with consequent alterations on appetite neuropeptides.
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.
authors.forename: Lígia
authors.initials: L
authors.lastname: Sousa-Ferreira
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Célia
authors.initials: C
authors.lastname: Aveleira
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.
authors.forename: Mariana
authors.initials: M
authors.lastname: Botelho
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Department of Biology and Environment University of Trás-os-Montes and Alto Douro, Vila Real, Portugal.
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Álvaro
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.
authors.forename: Luís
authors.initials: L
authors.lastname: Pereira de Almeida
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Cavadas
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000494:pharmacology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007031:Hypothalamus / Q000166:cytology* / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects* / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D051381:Rats; D059326:Serotonergic Neurons / Q000187:drug effects / Q000378:metabolism; D018874:Spheroids, Cellular / Q000187:drug effects; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D018687:Antidepressive Agents, Second-Generation; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D005473:Fluoxetine; D011333:Pro-Opiomelanocortin