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Intrahippocampal administration of the alpha-keto acids accumulating in maple syrup urine disease provokes learning deficits in rats.
Pharmacol Biochem Behav. 2004 Jan; 77(1):183-90.PB

Abstract

Learning disability is a common feature of patients affected by maple syrup urine disease (MSUD). However, the pathomechanisms underlying learning deficit in this disorder are poorly known. In the present study, we investigated the effect of acute administration of the alpha-keto acids accumulating in MSUD into the hippocampus on the behavior of rats in the open field and in the inhibitory avoidance tasks. Adult male Wistar rats received intrahippocampal injections of alpha-ketoisocaproic acid (KIC, 8 micromol), alpha-ketoisovaleric acid (KIV, 5 micromol), alpha-keto-beta-methylvaleric acid (KMV, 5 micromol), or NaCl (8 micromol) (controls) immediately after or 10 min before training. Testing session was performed 24 h later. Posttraining administration of the keto acids had no effect on learning in the open-field task. In contrast, pretraining administration of KIV and KMV impaired habituation in the open field. Similarly, pretraining administration of KIC, KIV, and KMV affected rat performance in the inhibitory avoidance task, suggesting disruption of acquisition. The results indicate that the alpha-keto acids accumulating in MSUD induce learning deficits in aversive and nonaversive tasks. We therefore suggest that these findings may be related to the psychomotor delay/mental retardation observed in MSUD, and may indicate the contribution of increased brain concentrations of these organic acids to the pathophysiology of the neurological dysfunction of MSUD patients.

Authors+Show Affiliations

Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, RS, Porto Alegre, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14724056

Citation

de Castro Vasques, Vilson, et al. "Intrahippocampal Administration of the Alpha-keto Acids Accumulating in Maple Syrup Urine Disease Provokes Learning Deficits in Rats." Pharmacology, Biochemistry, and Behavior, vol. 77, no. 1, 2004, pp. 183-90.
de Castro Vasques V, de Boer MA, Diligenti F, et al. Intrahippocampal administration of the alpha-keto acids accumulating in maple syrup urine disease provokes learning deficits in rats. Pharmacol Biochem Behav. 2004;77(1):183-90.
de Castro Vasques, V., de Boer, M. A., Diligenti, F., Brinco, F., Mallmann, F., Mello, C. F., & Wajner, M. (2004). Intrahippocampal administration of the alpha-keto acids accumulating in maple syrup urine disease provokes learning deficits in rats. Pharmacology, Biochemistry, and Behavior, 77(1), 183-90.
de Castro Vasques V, et al. Intrahippocampal Administration of the Alpha-keto Acids Accumulating in Maple Syrup Urine Disease Provokes Learning Deficits in Rats. Pharmacol Biochem Behav. 2004;77(1):183-90. PubMed PMID: 14724056.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intrahippocampal administration of the alpha-keto acids accumulating in maple syrup urine disease provokes learning deficits in rats. AU - de Castro Vasques,Vilson, AU - de Boer,Melissa Avila, AU - Diligenti,Felipe, AU - Brinco,Fabrício, AU - Mallmann,Fabrício, AU - Mello,Carlos Fernando, AU - Wajner,Moacir, PY - 2004/1/16/pubmed PY - 2004/9/17/medline PY - 2004/1/16/entrez SP - 183 EP - 90 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol Biochem Behav VL - 77 IS - 1 N2 - Learning disability is a common feature of patients affected by maple syrup urine disease (MSUD). However, the pathomechanisms underlying learning deficit in this disorder are poorly known. In the present study, we investigated the effect of acute administration of the alpha-keto acids accumulating in MSUD into the hippocampus on the behavior of rats in the open field and in the inhibitory avoidance tasks. Adult male Wistar rats received intrahippocampal injections of alpha-ketoisocaproic acid (KIC, 8 micromol), alpha-ketoisovaleric acid (KIV, 5 micromol), alpha-keto-beta-methylvaleric acid (KMV, 5 micromol), or NaCl (8 micromol) (controls) immediately after or 10 min before training. Testing session was performed 24 h later. Posttraining administration of the keto acids had no effect on learning in the open-field task. In contrast, pretraining administration of KIV and KMV impaired habituation in the open field. Similarly, pretraining administration of KIC, KIV, and KMV affected rat performance in the inhibitory avoidance task, suggesting disruption of acquisition. The results indicate that the alpha-keto acids accumulating in MSUD induce learning deficits in aversive and nonaversive tasks. We therefore suggest that these findings may be related to the psychomotor delay/mental retardation observed in MSUD, and may indicate the contribution of increased brain concentrations of these organic acids to the pathophysiology of the neurological dysfunction of MSUD patients. SN - 0091-3057 UR - https://www.unboundmedicine.com/medline/citation/14724056/Intrahippocampal_administration_of_the_alpha_keto_acids_accumulating_in_maple_syrup_urine_disease_provokes_learning_deficits_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091305703003241 DB - PRIME DP - Unbound Medicine ER -