Selective inhibition of phosphodiesterase 5 enhances glutamatergic synaptic plasticity and memory in mice

Subramaniam Uthayathas, Kodeeswaran Parameshwaran, Senthilkumar S. Karuppagounder, Manuj Ahuja, Muralikrishnan Dhanasekaran, Vishnu Suppiramaniam

Research output: Contribution to journalArticle

Abstract

Phosphodiesterases (PDEs) belong to a family of proteins that control metabolism of cyclic nucleotides. Targeting PDE5, for enhancing cellular function, is one of the therapeutic strategies for male erectile dysfunction. We have investigated whether in vivo inhibition of PDE5, which is expressed in several brain regions, will enhance memory and synaptic transmission in the hippocampus of healthy mice. We have found that acute administration of sildenafil, a specific PDE5 inhibitor, enhanced hippocampus-dependent memory tasks. To elucidate the underlying mechanism in the memory enhancement, effects of sildenafil on long-term potentiation (LTP) were measured. The level of LTP was significantly elevated, with concomitant increases in basal synaptic transmission, in mice treated with sildenafil (1 mg/kg/day) for 15 days compared to control mice. These results suggest that moderate PDE5 inhibition enhances memory by increasing synaptic plasticity and transmission in the hippocampus.

Original languageEnglish (US)
Pages (from-to)741-747
Number of pages7
JournalSynapse
Volume67
Issue number11
DOIs
StatePublished - Nov 1 2013

Keywords

  • Hippocampus
  • Memory
  • Phosphodiesterases
  • Sildenafil
  • Synaptic plasticity

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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    Uthayathas, S., Parameshwaran, K., Karuppagounder, S. S., Ahuja, M., Dhanasekaran, M., & Suppiramaniam, V. (2013). Selective inhibition of phosphodiesterase 5 enhances glutamatergic synaptic plasticity and memory in mice. Synapse, 67(11), 741-747. https://doi.org/10.1002/syn.21676