title: 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.affiliation: Department of Physiology, College of Medicine, Kyung Hee University, #1 Hoigi-dong, Dongdaemoon-gu, Seoul 130-701, Republic of Korea.
authors.forename: Il-Gyu
authors.initials: IG
authors.lastname: Ko
authors.forename: Mal-Soon
authors.initials: MS
authors.lastname: Shin
authors.forename: Bo-Kyun
authors.initials: BK
authors.lastname: Kim
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Kim
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Sung
authors.forename: Tae-Soo
authors.initials: TS
authors.lastname: Kim
authors.forename: Min-Chul
authors.initials: MC
authors.lastname: Shin
authors.forename: Han-Jin
authors.initials: HJ
authors.lastname: Cho
authors.forename: Sin-Chul
authors.initials: SC
authors.lastname: Kim
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Khae-Hawn
authors.initials: KH
authors.lastname: Kim
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Shin
authors.forename: Chang-Ju
authors.initials: CJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D000963:Antimetabolites; D017209:Apoptosis / Q000187:drug effects*; D001362:Avoidance Learning / Q000187:drug effects; D002545:Brain Ischemia / Q000473:pathology*; D001973:Bromodeoxyuridine; D002243:Carbolines / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D018891:Dentate Gyrus / Q000473:pathology; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008570:Memory, Short-Term / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D000068581:Tadalafil
chemical_list: D000963:Antimetabolites; D002243:Carbolines; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D000068581:Tadalafil; D053148:Caspase 3; D001973:Bromodeoxyuridine; D006152:Cyclic GMP