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 language | English |
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Pages (from-to) | 629-635 |
Number of pages | 7 |
Journal | Pharmacology Biochemistry and Behavior |
Volume | 91 |
Issue number | 4 |
DOIs | |
Publication status | Published - 2009 Feb |
Externally published | Yes |
Keywords
- Apoptosis
- Cell proliferation
- Cerebral ischemia
- Phosphodiesterase-5 inhibitor
- Short-term memory
- Tadalafil
- cGMP level
ASJC Scopus subject areas
- Biochemistry
- Toxicology
- Pharmacology
- Clinical Biochemistry
- Biological Psychiatry
- Behavioral Neuroscience