In Search of the Serotonin Role in the Contrasting Synapse Remodeling Induced by Fluoxetine in Cortical and Hippocampal Neurons

TRAETTA ME; LITVAK ET; MALLEVILLE CORPA MJ; UCCELLI NA; REINÉS A; CODAGNONE MG; ZÁRATE S

Córdoba

Congreso; XXXIII Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; 2018

Sociedad Argentina de Investigación en Neurociencias (SAN)

The antidepressant fluoxetine (FLX) is a specific serotonin(5HT) reuptake inhibitor (SSRI). We have previously showedthat behavioral benefits induced by FLX in experimentaldepression occur concomitantly with hippocampal changesin synapse morphology and number. FLX has also shown toincrease synapse number in the cerebral cortex of naiveanimals, an effect not shared by all SSRIs. The aim of thiswork was to study the in vitro profile of FLX-induced synapseremodeling in hippocampal and cortical neurons. To this aim,primary neuronal cultures obtained from embryonic (E18)and postnatal (P1-2) rats were exposed for 24 hr to FLX or5HT. Immunostaining of the dendritic marker MAP-2 and thesynaptic marker synaptophysin (SYN) were evaluated tostudy dendritic and synapse remodeling, respectively. In cortical neurons (DIV7), FLX treatment (1mM) increased SYNpuncta number and total puncta area without modifying thedentritic tree. This effect was mimicked by 5HT and blockedby ketanserin (5HT2R antagonist). In hippocampal neurons(DIV14), FLX treatment (0.1?1 mM) decreased SYN punctanumber and total puncta area and induced dendritic retraction. 5HT treatment failed to mimic FLX effect in hippocampal neurons. Our results indicate that FLX-induced synapseremodeling depends on the neuronal phenotype and suggestthat while FLX effect in cortical neurons is 5HT-mediated, itseems to involve a more complex mechanism in hippocampal neurons.