Down Syndrome Abstract
of the Month:
August 2007
Fluoxetine rescues deficient neurogenesis in hippocampus of the Ts65Dn mouse model for Down syndrome.
Clark S, Schwalbe J, Stasko MR, Yarowsky PJ, Costa AC.
Exp Neurol. 2006 Jul;200(1):256-61.
Dept. of Pharmacology and Exp. Therapeutics, Univ. of Maryland School of Medicine, Baltimore, MD, USA
Abstract:
The Ts65Dn mouse, an adult model of Down syndrome displays behavioral deficits consistent with a dysfunctional hippocampus, similar to that seen with DS. In looking for mechanisms underlying these performance deficits, we have assessed adult neurogenesis in the dentate gyrus of Ts65Dn. Under untreated conditions, Ts65Dn mice (2-5 months old) showed markedly fewer BrdU-labeled cells than euploid animals. Chronic antidepressant treatment for over 3 weeks with the serotonin selective reuptake inhibitor, fluoxetine, increased neurogenesis in the Ts65Dn to comparable levels seen in the euploid by augmenting both proliferation and survival of BrdU-labeled cells in the subgranular layer and granule cell layer of the hippocampus, respectively.
My comments:
It has been noted that the hippocampus, an area of the brain associated with learning and memory, is smaller and does not work as well in adults with DS compared to the general population. The mouse model for adults with DS, referred to as strain Ts65Dn, has the same feature, making it useful to study the hippocampus. It has also been noted that the hippocampus is one of the sites in the brain of both mice and men where neurogenesis occurs. Neurogenesis refers to both cell production and cell survival. Chronic use of antidepressants, such as fluoxetine, has been noted to increase neurogenesis.The authors of this study proposed that neurogenesis in the Ts65Dn mouse is decreased compared to other mice, and that the use of fluoxetine would increase neurogenesis in the hippocampus. They injected the Ts65Dn mice and the control mice with a substance called BrdU which was picked up in the hippocampal cells that were replicating. The Ts65Dn mice had significantly less neurogenesis in the hippocampus than the control (non-trisomy) mice.
The trisomy mice were then injected daily with fluoxetine for 24 days, after which they were found to have significantly more neurogenesis occuring. This research also showed that not only was there more proliferation, but there was also more cellular survival.
However, this study could not tell us which hippocampal cells were being created. It's possible that it could be the neurons, or hippocampal brain cells, or it could be the supportive glial cells. If it were the glial cells, we would not expect any change in brain function. The study also did not determine if the trisomy mice had any changes in behavior, so we do not know if the fluoxetine had any demonstrable effect in learning or memory. Until further studies are done, it is too early to recommend the routine use of fluoxetine (Prozac) in children or adults with Down syndrome for reasons other than depression.
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