title: Ascorbic acid prevents cognitive deficits caused by chronic administration of propionic acid to rats in the water maze.
abstract: Propionic acidemia is an inherited neurometabolic disorder characterized by progressive neurological deterioration with psychomotor delay/mental retardation, convulsions and coma, and whose pathophysiology is poorly unknown. In the present study, we investigated the effect of chronic administration (from the 5th to the 28th days of life) of propionic acid (PA), the major metabolite accumulating in tissues of patients affected by propionic acidemia, on the cognitive performance of adult rats in the Morris water maze task. PA doses ranged from 1.44 to 1.92 micromol/g body weight as a function of animal age. Control rats were treated with saline in the same volumes. Chronic postnatal days (5-28) PA treatment had no effect on body weight. However, it impaired spatial performance in the water maze. We also determined the effect of ascorbic acid (AA) administered, alone or combined with PA, on the same behavioral parameters in order to test whether free radicals could be responsible for the behavioral alterations observed in PA-treated animals. AA was able to prevent the behavioral alterations provoked by PA, implying that oxidative stress may be involved in these effects. Furthermore, we also investigated the total radical-trapping antioxidant potential (TRAP) in the hippocampus of the animals. We observed that TRAP was significantly reduced in the brain of propionic acidemic rats and that co-administration of AA prevented this effect. The results provide evidence that early PA treatment induces long-lasting behavioral deficits, which are possibly caused by oxygen reactive species generation, and suggest that oxidative stress may be involved in the neuropathology of propionic acidemia.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Av. Ramiro Barcelos, Porto Alegre, Brazil.
authors.forename: Leticia F
authors.initials: LF
authors.lastname: Pettenuzzo
authors.forename: Patrícia F
authors.initials: PF
authors.lastname: Schuck
authors.forename: Fernanda
authors.initials: F
authors.lastname: Fontella
authors.forename: Clóvis M D
authors.initials: CM
authors.lastname: Wannmacher
authors.forename: Angela T
authors.initials: AT
authors.lastname: Wyse
authors.forename: Carlos S
authors.initials: CS
authors.lastname: Dutra-Filho
authors.forename: Carlos Alexandre
authors.initials: CA
authors.lastname: Netto
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced / Q000517:prevention & control*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D011422:Propionates / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012193:Reversal Learning / Q000187:drug effects; D013550:Swimming / Q000502:physiology / Q000523:psychology
chemical_list: D016166:Free Radical Scavengers; D011422:Propionates; D017382:Reactive Oxygen Species; C029658:propionic acid; D001205:Ascorbic Acid