Fluoxetine in adulthood normalizes GABA release and rescues hippocampal synaptic plasticity and spatial memory in a mouse model of Down Syndrome

Neurobiology of Disease

Giovanni Cioni¹  Marco Milanese²  Tiziana Bonifacino²  Giambattista Bonanno²  Alessandro Sale³  Gabriele Sansevero³  Lamberto Maffei³  Tatjana Begenisic³  Laura Baroncelli³ 

[1] Department of Developmental Neuroscience, IRCCS Stella Maris and University of Pisa, Calambrone, Pisa I-56100, Italy;Department of Pharmacy, Section of Pharmacology and Toxicology Unit, University of Genova, Genova I-16148, Italy;Institute of Neuroscience CNR, Pisa I-56100, Italy;

关键词: Down syndrome;    Ts65Dn mice;    Fluoxetine;    Intellectual disability;    GABA;   

DOI  :  

来源: DOAJ

【 摘 要 】

Down syndrome (DS) is the most common genetic disorder associated with mental retardation. It has been repeatedly shown that Ts65Dn mice, the major animal model for DS, have severe cognitive and synaptic plasticity dysfunctions caused by excessive inhibition in their temporal lobe structures. Here we employed a multidisciplinary approach spanning from the behavioral to the electrophysiological and molecular level to investigate the effects elicited by fluoxetine on cognitive abilities, hippocampal synaptic plasticity and GABA release in adult Ts65Dn mice. We report that a chronic treatment with fluoxetine administered in the drinking water normalizes GABA release and promotes recovery of spatial memory abilities, spatial working memory for alternation, and hippocampal synaptic plasticity in adult Ts65Dn mice. Our findings might encourage new experimental attempts aimed at investigating the potential of fluoxetine for application in the treatment of major functional deficits in adult people with DS.

【 授权许可】

Unknown