TY - JOUR
T1 - Selective inhibition of phosphodiesterase 5 enhances glutamatergic synaptic plasticity and memory in mice
AU - Uthayathas, Subramaniam
AU - Parameshwaran, Kodeeswaran
AU - Karuppagounder, Senthilkumar S.
AU - Ahuja, Manuj
AU - Dhanasekaran, Muralikrishnan
AU - Suppiramaniam, Vishnu
PY - 2013/11
Y1 - 2013/11
N2 - 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.
AB - 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.
KW - Hippocampus
KW - Memory
KW - Phosphodiesterases
KW - Sildenafil
KW - Synaptic plasticity
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U2 - 10.1002/syn.21676
DO - 10.1002/syn.21676
M3 - Article
C2 - 23620198
AN - SCOPUS:84884211273
SN - 0887-4476
VL - 67
SP - 741
EP - 747
JO - Synapse
JF - Synapse
IS - 11
ER -