Chronic postnatal ornithine administration to rats provokes learning deficit in the open field task.
Hyperornithinemia is the biochemical hallmark of hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, an inherited metabolic disease clinically characterized by mental retardation whose pathogenesis is still poorly known. In the present work, we produced a chemical animal model of hyperornithinemia induced by a subcutaneous injection of saline-buffered Orn (2-5 μmol/g body weight) to rats. High brain Orn concentrations were achieved, indicating that Orn is permeable to the blood brain barrier. We then investigated the effect of early chronic postnatal administration of Orn on physical development and on the performance of adult rats in the open field, the Morris water maze and in the step down inhibitory avoidance tasks. Chronic Orn treatment had no effect on the appearance of coat, eye opening or upper incisor eruption, nor on the free-fall righting reflex and on the adult rat performance in the Morris water maze and in the inhibitory avoidance tasks, suggesting that physical development, aversive and spatial localization were not changed by Orn. However, Orn-treated rats did not habituate to the open field apparatus, implying a deficit of learning/memory. Motor activity was the same for Orn- and saline- injected animals. We also verified that Orn subcutaneous injections provoked lipid peroxidation in the brain, as determined by a significant increase of thiobarbituric acid-reactive substances levels. Our results indicate that chronic early postnatal hyperornithinemia may impair the central nervous system, causing minor disabilities which result in specific learning deficiencies.
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Rua Ramiro Barcelos, 2600 - Anexo, CEP: 90035-003, Porto Alegre, RS, Brazil.
Carolina Maso
CM
Viegas
Estela Natacha Brandt
EN
Busanello
Anelise Miotti
AM
Tonin
Mateus
M
Grings
Alana Pimentel
AP
Moura
Luciana
L
Ritter
Angela
A
Zanatta
Lisiane Aurélio
LA
Knebel
Vannessa Araujo
VA
Lobato
Letícia Ferreira
LF
Pettenuzzo
Carmen Regla
CR
Vargas
Guilhian
G
Leipnitz
Moacir
M
Wajner
D000592:Amino Acid Metabolism, Inborn Errors / Q000139:chemically induced* / Q000523:psychology; D000641:Ammonia / Q000097:blood; D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D002956:Citrulline / Q000031:analogs & derivatives / Q000097:blood; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D002658:Developmental Disabilities / Q000139:chemically induced; D004195:Disease Models, Animal; D006207:Half-Life; D007859:Learning Disabilities / Q000139:chemically induced* / Q000523:psychology*; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D057567:Memory, Long-Term / Q000187:drug effects; D009952:Ornithine / Q000493:pharmacokinetics / Q000633:toxicity*; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D017392:Thiobarbituric Acid Reactive Substances; C001352:homocitrulline; D002956:Citrulline; D000641:Ammonia; D009952:Ornithine