title: Fluoxetine in adulthood normalizes GABA release and rescues hippocampal synaptic plasticity and spatial memory in a mouse model of Down syndrome.
abstract: 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.
authors.affiliation: Institute of Neuroscience CNR, Pisa I-56100, Italy.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Begenisic
authors.affiliation: Institute of Neuroscience CNR, Pisa I-56100, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Baroncelli
authors.affiliation: Institute of Neuroscience CNR, Pisa I-56100, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Sansevero
authors.affiliation: Department of Pharmacy, Section of Pharmacology and Toxicology Unit, University of Genova, Genova I-16148, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Milanese
authors.affiliation: Department of Pharmacy, Section of Pharmacology and Toxicology Unit, University of Genova, Genova I-16148, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bonifacino
authors.affiliation: Department of Pharmacy, Section of Pharmacology and Toxicology Unit, University of Genova, Genova I-16148, Italy.
authors.forename: Giambattista
authors.initials: G
authors.lastname: Bonanno
authors.affiliation: Department of Developmental Neuroscience, IRCCS Stella Maris and University of Pisa, Calambrone, Pisa I-56100, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cioni
authors.affiliation: Institute of Neuroscience CNR, Pisa I-56100, Italy.
authors.forename: Lamberto
authors.initials: L
authors.lastname: Maffei
authors.affiliation: Institute of Neuroscience CNR, Pisa I-56100, Italy. Electronic address: sale@in.cnr.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sale
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology / Q000627:therapeutic use*; D001703:Biophysics; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000150:complications / Q000235:genetics / Q000473:pathology*; D004558:Electric Stimulation; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D066298:In Vitro Techniques; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000187:drug effects*; D021641:Recognition, Psychology / Q000187:drug effects; D013028:Space Perception / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D005680:gamma-Aminobutyric Acid
keywords: Down syndrome; Fluoxetine; GABA; Intellectual disability; Ts65Dn mice