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

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.

• Authors: 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
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 91 Issue 4 Pg. 629-35 (Feb 2009) ISSN: 0091-3057 [Print] United States
• PMID: 19010346 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites
• Carbolines
• Phosphodiesterase 5 Inhibitors
• Phosphodiesterase Inhibitors
• Tadalafil
• Caspase 3
• Bromodeoxyuridine
• Cyclic GMP

Topics

• Animals
• Antimetabolites
• Apoptosis (drug effects)
• Avoidance Learning (drug effects)
• Brain Ischemia (pathology)
• Bromodeoxyuridine
• Carbolines (pharmacology)
• Caspase 3 (metabolism)
• Cyclic GMP (metabolism)
• Dentate Gyrus (pathology)
• Gerbillinae
• Hippocampus (drug effects, pathology)
• Immunohistochemistry
• In Situ Nick-End Labeling
• Memory, Short-Term (drug effects)
• Neurons (drug effects, pathology)
• Phosphodiesterase 5 Inhibitors
• Phosphodiesterase Inhibitors (pharmacology)
• Tadalafil