title: Effects of steroid hormones on (Na+, K+)-ATPase activity inhibition-induced amnesia on the step-through passive avoidance task in gonadectomized mice.
abstract: Inhibition of sodium-potassium adenosine 5'-triphosphatase ((Na(+), K(+))-ATPase) activity causes edema and cell death in the central nervous system, and impairment of learning and memory. Several sex steroid hormones have a protective effect against neuronal cell damage and the hypofunction of learning and memory. To examine the possible roles and mechanism of action of steroid hormones against amnesia induced by ouabain, an inhibitor of (Na(+), K(+))-ATPase, gonadectomized male mice were administrated ouabain (0.1 microg per mouse) intracisternally (i.cist.), and the learning and memory abilities of the mice were assessed by a step-through passive avoidance task. Subcutaneous (s.c.) administration of 17beta-estradiol (betaE2; 10 microg kg(-1)) or testosterone (TES; 1 mg kg(-1)) improved the memory impairment induced by ouabain, while administration of dihydrotestosterone (1 mg kg(-1)) or corticosterone (COR) (1 mg kg(-1)) did not. Treatment with the estradiol receptor antagonists, tamoxifen (TAM) (10 mg kg(-1); s.c. or 0.1 microg; i.cist.) and 4-hydroxytamoxifen (10 mg kg(-1); s.c.), or the androgen receptor antagonist, cyproterone (10 mg kg(-1); s.c. or 1 microg; i.cist.), did not influence the protective effect of betaE2 or TES on ouabain-induced amnesia. Moreover, we studied the effects of several free radical scavengers-17alpha-estradiol (10 microg kg(-1); s.c.), alpha-tocopherol (VE: 200 mg kg(-1); per os (p.o.), ascorbic acid (VC: 200 mg kg(-1); p.o.), or VE+VC (200 mg kg(-1) each; p.o.)-on ouabain-induced amnesia, and compared those effects with that of betaE2. The administration of free radical scavengers had no significant effect on memory impairment. These results indicate that betaE2 and TES ameliorate the amnesia induced by inhibition of (Na(+), K(+))-ATPase activity, and that the protective effect of betaE2 is caused by a non-genomic, rather than a genomic effect or a radical scavenging action. Additionally, the ameliorative effect of TES does not appear to involve free radical scavenging, but its aromatization to estrogen could contribute to the non-genomic action of betaE2.
authors.affiliation: Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka, Kagoshima 890-8544, Japan. tomsato@dentb.hal.kagoshima-u.ac.jp
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Sato
authors.forename: Koh ichi
authors.initials: Ki
authors.lastname: Tanaka
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Ohnishi
authors.forename: Toyonori
authors.initials: T
authors.lastname: Teramoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Irifune
authors.forename: Takashige
authors.initials: T
authors.lastname: Nishikawa
mesh_terms: D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy*; D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D002369:Castration; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology; D020011:Protective Agents / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013997:Time Factors
chemical_list: D000726:Androgen Antagonists; D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D016166:Free Radical Scavengers; D012739:Gonadal Steroid Hormones; D020011:Protective Agents; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase