Tadalafil improves short-term memory by suppressing ischemia-induced apoptosis of hippocampal neuronal cells in gerbils

Il Gyu Ko, Mal Soon Shin, Bo Kyun Kim, Sung Eun Kim, Yun Hee Sung, Tae Soo Kim, Min Chul Shin, Han Jin Cho, Sin Chul Kim, Sang Hoon Kim, Khae Hawn Kim, Dong Hoon Shin, Chang Ju Kim

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Cerebral ischemia resulting from transient or permanent cerebral artery occlusion leads to neuronal cell death, and eventually causes neurological impairments. Tadalafil (Cialis®) is a long-acting phosphodiesterase type-5 (PDE-5) inhibitor used to treat erectile dysfunction. The therapeutic effects of PDE-5 inhibitors on chronic obstructive pulmonary disease, prostate hyperplasia, hypertension, and coronary heart disease have been reported. The present study investigated the effects of tadalafil on short-term memory, cyclic guanosine monophosphate (cGMP) level, apoptotic neuronal cell death, and cell proliferation in the hippocampus following transient global ischemia in gerbils. For this study, a step-down avoidance task, cGMP assay, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, and immunohistochemistry for caspase-3 and 5-bromo-2′-deoxyuridine were performed. The results revealed that ischemic injury increased apoptotic neuronal cell death in the hippocampal CA1 region, impaired short-term memory, and decreased cGMP level. Ischemic injury enhanced cell proliferation in the hippocampal dentate gyrus. Tadalafil treatment improved short-term memory by suppressing ischemia-induced apoptotic neuronal cell death in the hippocampal CA1 region, and decreased cGMP level. Also, tadalafil suppressed the ischemia-induced increase in cell proliferation in the hippocampal dentate gyrus. We showed that tadalafil can overcome ischemia-induced apoptotic neuronal cell death, thus facilitates recovery following ischemic cerebral injury.

Original languageEnglish
Pages (from-to)629-635
Number of pages7
JournalPharmacology Biochemistry and Behavior
Volume91
Issue number4
DOIs
Publication statusPublished - 2009 Feb 1
Externally publishedYes

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Gerbillinae
Short-Term Memory
Cell death
Ischemia
Cyclic GMP
Apoptosis
Cell Death
Data storage equipment
Cell proliferation
Hippocampal CA1 Region
Phosphodiesterase 5 Inhibitors
Parahippocampal Gyrus
Dentate Gyrus
Cell Proliferation
Assays
Wounds and Injuries
Pulmonary diseases
Cerebral Arteries
DNA Nucleotidylexotransferase
Transient Ischemic Attack

Keywords

  • Apoptosis
  • Cell proliferation
  • Cerebral ischemia
  • cGMP level
  • Phosphodiesterase-5 inhibitor
  • Short-term memory
  • Tadalafil

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

Cite this

Tadalafil improves short-term memory by suppressing ischemia-induced apoptosis of hippocampal neuronal cells in gerbils. / Ko, Il Gyu; Shin, Mal Soon; Kim, Bo Kyun; Kim, Sung Eun; Sung, Yun Hee; Kim, Tae Soo; Shin, Min Chul; Cho, Han Jin; Kim, Sin Chul; Kim, Sang Hoon; Kim, Khae Hawn; Shin, Dong Hoon; Kim, Chang Ju.

In: Pharmacology Biochemistry and Behavior, Vol. 91, No. 4, 01.02.2009, p. 629-635.

Research output: Contribution to journalArticle

Ko, IG, Shin, MS, Kim, BK, Kim, SE, Sung, YH, Kim, TS, Shin, MC, Cho, HJ, Kim, SC, Kim, SH, Kim, KH, Shin, DH & Kim, CJ 2009, 'Tadalafil improves short-term memory by suppressing ischemia-induced apoptosis of hippocampal neuronal cells in gerbils', Pharmacology Biochemistry and Behavior, vol. 91, no. 4, pp. 629-635. https://doi.org/10.1016/j.pbb.2008.10.009
Ko, Il Gyu ; Shin, Mal Soon ; Kim, Bo Kyun ; Kim, Sung Eun ; Sung, Yun Hee ; Kim, Tae Soo ; Shin, Min Chul ; Cho, Han Jin ; Kim, Sin Chul ; Kim, Sang Hoon ; Kim, Khae Hawn ; Shin, Dong Hoon ; Kim, Chang Ju. / Tadalafil improves short-term memory by suppressing ischemia-induced apoptosis of hippocampal neuronal cells in gerbils. In: Pharmacology Biochemistry and Behavior. 2009 ; Vol. 91, No. 4. pp. 629-635.
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AU - Sung, Yun Hee

AU - Kim, Tae Soo

AU - Shin, Min Chul

AU - Cho, Han Jin

AU - Kim, Sin Chul

AU - Kim, Sang Hoon

AU - Kim, Khae Hawn

AU - Shin, Dong Hoon

AU - Kim, Chang Ju

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AB - Cerebral ischemia resulting from transient or permanent cerebral artery occlusion leads to neuronal cell death, and eventually causes neurological impairments. Tadalafil (Cialis®) is a long-acting phosphodiesterase type-5 (PDE-5) inhibitor used to treat erectile dysfunction. The therapeutic effects of PDE-5 inhibitors on chronic obstructive pulmonary disease, prostate hyperplasia, hypertension, and coronary heart disease have been reported. The present study investigated the effects of tadalafil on short-term memory, cyclic guanosine monophosphate (cGMP) level, apoptotic neuronal cell death, and cell proliferation in the hippocampus following transient global ischemia in gerbils. For this study, a step-down avoidance task, cGMP assay, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, and immunohistochemistry for caspase-3 and 5-bromo-2′-deoxyuridine were performed. The results revealed that ischemic injury increased apoptotic neuronal cell death in the hippocampal CA1 region, impaired short-term memory, and decreased cGMP level. Ischemic injury enhanced cell proliferation in the hippocampal dentate gyrus. Tadalafil treatment improved short-term memory by suppressing ischemia-induced apoptotic neuronal cell death in the hippocampal CA1 region, and decreased cGMP level. Also, tadalafil suppressed the ischemia-induced increase in cell proliferation in the hippocampal dentate gyrus. We showed that tadalafil can overcome ischemia-induced apoptotic neuronal cell death, thus facilitates recovery following ischemic cerebral injury.

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