title: Neurodevelopmental and cognitive behavior of glutaryl-CoA dehydrogenase deficient knockout mice.
abstract: OBJECTIVE
  The establishment of a genetic knockout murine model of glutaric acidemia type I (GAI) with complete loss of glutaryl-CoA dehydrogenase (GCDH) activity has been used to investigate the pathological mechanisms underlying neurological symptoms in this disorder. However, very little has been reported on the neurobehavior of GCDH deficient mice (Gcdh(-/-)).
  
  
  METHODS
  In the present study we evaluated physical (body and weight gain) and neuromotor development (appearance of coat, upper incisor eruption, eye-opening day, motor coordination, muscular strength and climbing), as well as cognitive behavior (inhibitory avoidance) in Gcdh(-/-), as compared to wild type (WT) mice.
  
  
  RESULTS
  We found that Gcdh(-/-) mice did not differ in body and weight gain, appearance of coat, upper incisor eruption, motor coordination and muscular strength, but had a significant delayed eye opening, implying a mild impairment of neurodevelopment in these animals. Furthermore, the climbing behavior was significantly higher in Gcdh(-/-) as compared to WT mice, suggesting an altered dopaminergic function. Finally, Gcdh(-/-) mice presented a deficit of short- and long-term memories in the inhibitory avoidance task.
  
  
  CONCLUSIONS
  Although it is difficult to extrapolate the present findings to the human condition, our present data are particularly interesting in view of the psychomotor/mental delay that occurs in a significant number of GAI patients with no previous history of acute encephalopathy with striatum destruction. Strict and early treatment possibly associated with novel therapies seems therefore important to prevent learning/memory disabilities in GAI patients.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Estela Natacha Brandt
authors.initials: EN
authors.lastname: Busanello
authors.forename: Letícia
authors.initials: L
authors.lastname: Pettenuzzo
authors.forename: Paulo Henrique
authors.initials: PH
authors.lastname: Botton
authors.forename: Pablo
authors.initials: P
authors.lastname: Pandolfo
authors.forename: Diogo Onofre Gomes
authors.initials: DO
authors.lastname: de Souza
authors.forename: Michael
authors.initials: M
authors.lastname: Woontner
authors.forename: Stephen
authors.initials: S
authors.lastname: Goodman
authors.forename: David
authors.initials: D
authors.lastname: Koeller
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D004195:Disease Models, Animal; D050770:Glutaryl-CoA Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics / Q000254:growth & development / Q000502:physiology; D053580:Muscle Strength / Q000235:genetics / Q000502:physiology; D017288:Pain Threshold / Q000502:physiology; D004856:Postural Balance / Q000235:genetics / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology
chemical_list: D050770:Glutaryl-CoA Dehydrogenase