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Early pharmacotherapy with fluoxetine rescues dendritic pathology in the Ts65Dn mouse model of down syndrome.
Brain Pathol. 2013 Mar; 23(2):129-43.BP

Abstract

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 P3-P15, 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.

Authors+Show Affiliations

Department of Human and General Physiology, University of Bologna, Bologna, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22817700

Citation

Guidi, Sandra, et al. "Early Pharmacotherapy With Fluoxetine Rescues Dendritic Pathology in the Ts65Dn Mouse Model of Down Syndrome." Brain Pathology (Zurich, Switzerland), vol. 23, no. 2, 2013, pp. 129-43.
Guidi S, Stagni F, Bianchi P, et al. Early pharmacotherapy with fluoxetine rescues dendritic pathology in the Ts65Dn mouse model of down syndrome. Brain Pathol. 2013;23(2):129-43.
Guidi, S., Stagni, F., Bianchi, P., Ciani, E., Ragazzi, E., Trazzi, S., Grossi, G., Mangano, C., Calzà, L., & Bartesaghi, R. (2013). Early pharmacotherapy with fluoxetine rescues dendritic pathology in the Ts65Dn mouse model of down syndrome. Brain Pathology (Zurich, Switzerland), 23(2), 129-43. https://doi.org/10.1111/j.1750-3639.2012.00624.x
Guidi S, et al. Early Pharmacotherapy With Fluoxetine Rescues Dendritic Pathology in the Ts65Dn Mouse Model of Down Syndrome. Brain Pathol. 2013;23(2):129-43. PubMed PMID: 22817700.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Early pharmacotherapy with fluoxetine rescues dendritic pathology in the Ts65Dn mouse model of down syndrome. AU - Guidi,Sandra, AU - Stagni,Fiorenza, AU - Bianchi,Patrizia, AU - Ciani,Elisabetta, AU - Ragazzi,Elena, AU - Trazzi,Stefania, AU - Grossi,Gabriele, AU - Mangano,Chiara, AU - Calzà,Laura, AU - Bartesaghi,Renata, Y1 - 2012/09/03/ PY - 2012/05/07/received PY - 2012/07/15/accepted PY - 2012/7/24/entrez PY - 2012/7/24/pubmed PY - 2013/8/16/medline SP - 129 EP - 43 JF - Brain pathology (Zurich, Switzerland) JO - Brain Pathol. VL - 23 IS - 2 N2 - 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 P3-P15, 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. SN - 1750-3639 UR - https://www.unboundmedicine.com/medline/citation/22817700/full_citation/Early_pharmacotherapy_with_fluoxetine_rescues_dendritic_pathology_in_the_Ts65Dn_mouse_model_of_Down_syndrome_ L2 - https://doi.org/10.1111/j.1750-3639.2012.00624.x DB - PRIME DP - Unbound Medicine ER -