Effects of citalopram on sutural and calvarial cell processes

Emily Durham, Serena Jen, Lin Wang, Joseph Nasworthy, Mohammed Elsalanty, Seth Weinberg, Jack Yu, James Cray

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The use of selective serotonin reuptake inhibitors (SSRIs) for the treatment of depression during pregnancy is suggested to increase the incidence of craniofacial abnormalities including craniosynostosis. Little is known about this mechanism, however based on previous data we propose a mechanism that affects cell cycle. Excessive proliferation, and reduction in apoptosis may lead to hyperplasia within the suture that may allow for differentiation, bony infiltration, and fusion. Here we utilized in vivo and in vitro analysis to investigate this proposed phenomenon. For in vivo analysis we used C57BL-6 wild-type breeders treated with a clinical dose of citalopram during the third trimester of pregnancy to produce litters exposed to the SSRI citalopram in utero. At post-natal day 15 sutures were harvested from resulting pups and subjected to histomorphometric analysis for proliferation (PCNA) and apoptosis (TUNEL). For in vitro studies, we used mouse calvarial pre-osteoblast cells (MC3T3-E1) to assess proliferation (MTS), apoptosis (Caspase 3/7-activity), and gene expression after exposure to titrated doses of citalopram. In vivo analysis for PCNA suggested segregation of effect by location, with the sagittal suture, showing a statistically significant increase in proliferative response. The coronal suture was not similarly affected, however there was a decrease in apoptotic activity at the dural edge as compared to the periosteal edge. No differences in apoptosis by suture or area due to SSRI exposure were observed. In vitro results suggest citalopram exposure increased proliferation and proliferative gene expression, and decreased apoptosis of the MC3T3-E1 cells. Decreased apoptosis was not confirmed in vivo however, an increase in proliferation without a concomitant increase in apoptosis is still defined as hyperplasia. Thus prenatal SSRI exposure may exert a negative effect on post-natal growth through a hyperplasia effect at the cranial growth sites perhaps leading to clinically significant craniofacial abnormalities.

Original languageEnglish (US)
Article numbere0139719
JournalPloS one
Volume10
Issue number10
DOIs
StatePublished - Oct 2 2015

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Citalopram
apoptosis
sutures
Apoptosis
Sutures
Serotonin Uptake Inhibitors
serotonin
Craniofacial Abnormalities
hyperplasia
Hyperplasia
cells
Proliferating Cell Nuclear Antigen
Gene expression
pregnancy
Caspase 7
Gene Expression
Craniosynostoses
gene expression
osteoblasts
Osteoblasts

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Durham, E., Jen, S., Wang, L., Nasworthy, J., Elsalanty, M., Weinberg, S., ... Cray, J. (2015). Effects of citalopram on sutural and calvarial cell processes. PloS one, 10(10), [e0139719]. https://doi.org/10.1371/journal.pone.0139719

Effects of citalopram on sutural and calvarial cell processes. / Durham, Emily; Jen, Serena; Wang, Lin; Nasworthy, Joseph; Elsalanty, Mohammed; Weinberg, Seth; Yu, Jack; Cray, James.

In: PloS one, Vol. 10, No. 10, e0139719, 02.10.2015.

Research output: Contribution to journalArticle

Durham, E, Jen, S, Wang, L, Nasworthy, J, Elsalanty, M, Weinberg, S, Yu, J & Cray, J 2015, 'Effects of citalopram on sutural and calvarial cell processes', PloS one, vol. 10, no. 10, e0139719. https://doi.org/10.1371/journal.pone.0139719
Durham E, Jen S, Wang L, Nasworthy J, Elsalanty M, Weinberg S et al. Effects of citalopram on sutural and calvarial cell processes. PloS one. 2015 Oct 2;10(10). e0139719. https://doi.org/10.1371/journal.pone.0139719
Durham, Emily ; Jen, Serena ; Wang, Lin ; Nasworthy, Joseph ; Elsalanty, Mohammed ; Weinberg, Seth ; Yu, Jack ; Cray, James. / Effects of citalopram on sutural and calvarial cell processes. In: PloS one. 2015 ; Vol. 10, No. 10.
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