title: Concurrent folate treatment prevents Na+,K+-ATPase activity inhibition and memory impairments caused by chronic hyperhomocysteinemia during rat development.
abstract: We investigated the hypothesis that folate administration would prevent hyperhomocysteinemia-induced memory deficits and Na(+),K(+)-ATPase activity inhibition. Chronic hyperhomocysteinemia was induced from the 6th to the 28th day of life by subcutaneous injection of homocysteine (0.3-0.6 micromol/g), twice a day; control Wistar rats received the same volume of saline solution (0.9% NaCl). Half of the homocysteine- and saline-treated groups also received intraperitoneal administration of folate (0.011 micromol/g) from the 6th to the 28th day of life. A group of animals was killed 12 h after the last injection, plasma and parietal cortex were collected for biochemical analysis. Another group stayed at Central Animal House until 60th day of life, when the rats were submitted to behavioral testing in water maze or were killed for evaluation of cortical Na(+),K(+)-ATPase activity. Results showed that hyperhomocysteinemia impaired reference memory for platform location, as assessed by fewer crossings to the platform place and increased latency for the first crossing, when compared to controls. In the working memory task homocysteine-treated animals also needed more time to find the platform. We also observed that Na(+),K(+)-ATPase activity was reduced in parietal cortex of hyperhomocysteinemic rats sacrificed 12h after the last injection of homocysteine (29-day-old rats). In contrast, this enzyme was not altered when the rats were sacrificed 31 days after the treatment (60-day-old rats). Hyperhomocysteinemic rats treated with folate had all those impairments prevented, an effect probably related to folate antioxidant properties.
authors.affiliation: Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Matté
authors.forename: Emilene B S
authors.initials: EB
authors.lastname: Scherer
authors.forename: Francieli M
authors.initials: FM
authors.lastname: Stefanello
authors.forename: Alethéa G
authors.initials: AG
authors.lastname: Barschak
authors.forename: Carmen R
authors.initials: CR
authors.lastname: Vargas
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Netto
authors.forename: Angela T S
authors.initials: AT
authors.lastname: Wyse
mesh_terms: D000375:Aging / Q000523:psychology; D000818:Animals; D002908:Chronic Disease; D003071:Cognition / Q000187:drug effects; D005492:Folic Acid / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood / Q000633:toxicity; D020138:Hyperhomocysteinemia / Q000209:etiology* / Q000517:prevention & control*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000209:etiology* / Q000517:prevention & control*; D008570:Memory, Short-Term / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010296:Parietal Lobe / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013028:Space Perception / Q000187:drug effects; D013570:Synaptic Membranes / Q000187:drug effects; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014815:Vitamins / Q000627:therapeutic use*
chemical_list: D009419:Nerve Tissue Proteins; D017392:Thiobarbituric Acid Reactive Substances; D014815:Vitamins; D006710:Homocysteine; D005492:Folic Acid; D000254:Sodium-Potassium-Exchanging ATPase