Open AccessEarly Pharmacotherapy with Fluoxetine Rescues Dendritic Pathology in the Ts65Dn Mouse Model of D own Syndrome
Author(s) -
Guidi Sandra,
Stagni Fiorenza,
Bianchi Patrizia,
Ciani Elisabetta,
Ragazzi Elena,
Trazzi Stefania,
Grossi Gabriele,
Mangano Chiara,
Calzà Laura,
Bartesaghi Renata
Publication year - 2013
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2012.00624.x
Subject(s) - fluoxetine , neurogenesis , dentate gyrus , dendritic spine , serotonin reuptake inhibitor , serotonin , medicine , neuroscience , psychology , hippocampal formation , biology , receptor
Down syndrome DS is a genetic pathology characterized by brain hypotrophy and severe cognitive impairment. Although defective neurogenesis is an important determinant of mental disability, a severe dendritic pathology appears to be an equally important factor. A previous study showed that fluoxetine, a selective serotonin reuptake inhibitor, fully restores neurogenesis in the Ts65Dn mouse model of DS . The goal of the current study was to establish whether fluoxetine also restores dendritic development. In mice aged 45 days, treated with fluoxetine in the postnatal period P 3– P 15, we examined the dendritic arbor of the granule cells of the dentate gyrus ( DG ). The granule cells of trisomic mice had a severely hypotrophic dendritic arbor, fewer spines and a reduced innervation than euploid mice. Treatment with fluoxetine fully restored all these defects. In Ts65Dn mice, we found reduced levels of serotonin that were restored by treatment. Results show that a pharmacotherapy with fluoxetine is able to rescue not only the number of granule neurons but also their “quality” in terms of correct maturation and connectivity. These findings strongly suggest that fluoxetine may be a drug of choice for the improvement of the major defects in the DS brain and, possibly, of mental retardation.