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Role of the 5-HT4 receptor in chronic fluoxetine treatment-induced neurogenic activity and granule cell dematuration in the dentate gyrus

Overview of attention for article published in Molecular Brain, May 2015
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Title
Role of the 5-HT4 receptor in chronic fluoxetine treatment-induced neurogenic activity and granule cell dematuration in the dentate gyrus
Published in
Molecular Brain, May 2015
DOI 10.1186/s13041-015-0120-3
Pubmed ID
Authors

Yuki Imoto, Toshihiko Kira, Mamiko Sukeno, Naoya Nishitani, Kazuki Nagayasu, Takayuki Nakagawa, Shuji Kaneko, Katsunori Kobayashi, Eri Segi-Nishida

Abstract

Chronic treatment with selective serotonin (5-HT) reuptake inhibitors (SSRIs) facilitates adult neurogenesis and reverses the state of maturation in mature granule cells (GCs) in the dentate gyrus (DG) of the hippocampus. Recent studies have suggested that the 5-HT4 receptor is involved in both effects. However, it is largely unknown how the 5-HT4 receptor mediates neurogenic effects in the DG and, how the neurogenic and dematuration effects of SSRIs interact with each other. We addressed these issues using 5-HT4 receptor knockout (5-HT4R KO) mice. Expression of the 5-HT4 receptor was detected in mature GCs but not in neuronal progenitors of the DG. We found that chronic treatment with the SSRI fluoxetine significantly increased cell proliferation and the number of doublecortin-positive cells in the DG of wild-type mice, but not in 5-HT4R KO mice. We then examined the correlation between the increased neurogenesis and the dematuration of GCs. As reported previously, reduced expression of calbindin in the DG, as an index of dematuration, by chronic fluoxetine treatment was observed in wild-type mice but not in 5-HT4R KO mice. The proliferative effect of fluoxetine was inversely correlated with the expression level of calbindin in the DG. The expression of neurogenic factors in the DG, such as brain derived neurotrophic factor (Bdnf), was also associated with the progression of dematuration. These results indicate that the neurogenic effects of fluoxetine in the DG are closely associated with the progression of dematuration of GCs. In contrast, the DG in which neurogenesis was impaired by irradiation still showed significant reduction of calbindin expression by chronic fluoxetine treatment, suggesting that dematuration of GCs by fluoxetine does not require adult neurogenesis in the DG. We demonstrated that the 5-HT4 receptor plays an important role in fluoxetine-induced adult neurogenesis in the DG in addition to GC dematuration, and that these phenomena are closely associated. Our results suggest that 5-HT4 receptor-mediated phenotypic changes, including dematuration in mature GCs, underlie the neurogenic effect of SSRIs in the DG, providing new insight into the cellular mechanisms of the neurogenic actions of SSRIs in the hippocampus.

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The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 52 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 52 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 14 27%
Student > Master 9 17%
Student > Bachelor 7 13%
Researcher 5 10%
Professor > Associate Professor 3 6%
Other 6 12%
Unknown 8 15%
Readers by discipline Count As %
Neuroscience 14 27%
Agricultural and Biological Sciences 10 19%
Medicine and Dentistry 6 12%
Biochemistry, Genetics and Molecular Biology 3 6%
Chemistry 3 6%
Other 5 10%
Unknown 11 21%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 April 2016.
All research outputs
#4,730,607
of 8,756,523 outputs
Outputs from Molecular Brain
#271
of 455 outputs
Outputs of similar age
#121,783
of 222,054 outputs
Outputs of similar age from Molecular Brain
#13
of 20 outputs
Altmetric has tracked 8,756,523 research outputs across all sources so far. This one is in the 27th percentile – i.e., 27% of other outputs scored the same or lower than it.
So far Altmetric has tracked 455 research outputs from this source. They receive a mean Attention Score of 4.1. This one is in the 29th percentile – i.e., 29% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 222,054 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 35th percentile – i.e., 35% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 20 others from the same source and published within six weeks on either side of this one. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.