In vivo and in vitro effects of vortioxetine on molecules associated with neuroplasticity

Pirathiv Kugathasan, Jessica Waller, Ligia Westrich, Aicha Abdourahman, Joseph A. Tamm, Alan L. Pehrson, Elena Dale, Maria E. Gulinello, Connie Sanchez, Yan Li

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Neuroplasticity is fundamental for brain functions, abnormal changes of which are associated with mood disorders and cognitive impairment. Neuroplasticity can be affected by neuroactive medications and by aging. Vortioxetine, a multimodal antidepressant, has shown positive effects on cognitive functions in both pre-clinical and clinical studies. In rodent studies, vortioxetine increases glutamate neurotransmission, promotes dendritic branching and spine maturation, and elevates hippocampal expression of the activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) at the transcript level. The present study aims to assess the effects of vortioxetine on several neuroplasticity-related molecules in different experimental systems. Chronic (1 month) vortioxetine increased Arc/Arg3.1 protein levels in the cortical synaptosomes of young and middle-aged mice. In young mice, this was accompanied by an increase in actin-depolymerizing factor (ADF)/cofilin serine 3 phosphorylation without altering the total ADF/cofilin protein level, and an increase in the GluA1 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor phosphorylation at serine 845 (S845) without altering serine 831 (S831) GluA1 phosphorylation nor the total GluA1 protein level. Similar effects were detected in cultured rat hippocampal neurons: Acute vortioxetine increased S845 GluA1 phosphorylation without changing S831 GluA1 phosphorylation or the total GluA1 protein level. These changes were accompanied by an increase in α subunit of Ca2+/calmodulin-dependent kinase (CaMKIIα) phosphorylation (at threonine 286) without changing the total CaMKIIα protein level in cultured neurons. In addition, chronic (1 month) vortioxetine, but not fluoxetine, restored the age-associated reduction in Arc/Arg3.1 and c-Fos transcripts in the frontal cortex of middle-aged mice. Taken together, these results demonstrated that vortioxetine modulates molecular targets that are related to neuroplasticity.

Original languageEnglish (US)
Pages (from-to)365-376
Number of pages12
JournalJournal of Psychopharmacology
Volume31
Issue number3
DOIs
StatePublished - Mar 1 2017

Fingerprint

Neuronal Plasticity
Serine
Phosphorylation
Destrin
Actin Depolymerizing Factors
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Proteins
Neurons
Dendritic Spines
Calcium-Calmodulin-Dependent Protein Kinases
AMPA Receptors
Synaptosomes
Fluoxetine
Frontal Lobe
Threonine
vortioxetine
In Vitro Techniques
Cytoskeleton
Mood Disorders
Synaptic Transmission

Keywords

  • Activity-regulated cytoskeleton-associated protein
  • antidepressant
  • calmodulin-dependent kinase
  • cofilin
  • fluoxetine
  • GluA1
  • neuroplasticity
  • phosphorylation
  • protein expression
  • vortioxetine

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Kugathasan, P., Waller, J., Westrich, L., Abdourahman, A., Tamm, J. A., Pehrson, A. L., ... Li, Y. (2017). In vivo and in vitro effects of vortioxetine on molecules associated with neuroplasticity. Journal of Psychopharmacology, 31(3), 365-376. https://doi.org/10.1177/0269881116667710

In vivo and in vitro effects of vortioxetine on molecules associated with neuroplasticity. / Kugathasan, Pirathiv; Waller, Jessica; Westrich, Ligia; Abdourahman, Aicha; Tamm, Joseph A.; Pehrson, Alan L.; Dale, Elena; Gulinello, Maria E.; Sanchez, Connie; Li, Yan.

In: Journal of Psychopharmacology, Vol. 31, No. 3, 01.03.2017, p. 365-376.

Research output: Contribution to journalArticle

Kugathasan, P, Waller, J, Westrich, L, Abdourahman, A, Tamm, JA, Pehrson, AL, Dale, E, Gulinello, ME, Sanchez, C & Li, Y 2017, 'In vivo and in vitro effects of vortioxetine on molecules associated with neuroplasticity', Journal of Psychopharmacology, vol. 31, no. 3, pp. 365-376. https://doi.org/10.1177/0269881116667710
Kugathasan P, Waller J, Westrich L, Abdourahman A, Tamm JA, Pehrson AL et al. In vivo and in vitro effects of vortioxetine on molecules associated with neuroplasticity. Journal of Psychopharmacology. 2017 Mar 1;31(3):365-376. https://doi.org/10.1177/0269881116667710
Kugathasan, Pirathiv ; Waller, Jessica ; Westrich, Ligia ; Abdourahman, Aicha ; Tamm, Joseph A. ; Pehrson, Alan L. ; Dale, Elena ; Gulinello, Maria E. ; Sanchez, Connie ; Li, Yan. / In vivo and in vitro effects of vortioxetine on molecules associated with neuroplasticity. In: Journal of Psychopharmacology. 2017 ; Vol. 31, No. 3. pp. 365-376.
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