Exposure to leucine alters glutamate levels and leads to memory and social impairment in zebrafish

• Published in: Metabolic brain disease Vol. 37; no. 8; pp. 2925 - 2935
• Main Authors: da Silva Lemos, Isabela, Wessler, Leticia Burato, Duarte, Mariane Bernardo, da Silva, Guilherme Lodetti, Bernardo, Henrique Teza, Candiotto, Gabriela, Torres, Carolina Antunes, Petronilho, Fabricia, Rico, Eduardo Pacheco, Streck, Emilio Luiz
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-12-2022; Springer Nature B.V
• Subjects: Amino acids; Animal cognition; Anxiety; Apoptosis; Aquariums; Behavior; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain damage; Brain injury; Central nervous system; Chain branching; Chains; Cognitive ability; Danio rerio; Enzymes; High performance liquid chromatography; Impairment; Intellectual disabilities; Isoleucine; Laboratory animals; Leucine; Liquid chromatography; Maple syrup; Maple syrup urine disease; Memory; Metabolic Diseases; Metabolic disorders; Metabolism; Neurology; Neurosciences; Neurotoxicity; Object recognition; Oncology; Original Article; Pattern recognition; Seizures; Signs and symptoms; Social behavior; Syrup; Urine; Valine; Zebrafish; Maple syrup urine disease; Zebrafish; Behavior; Glutamate; Alpha-branched-chain amino acids
• ISSN: 0885-7490; 1573-7365
• DOI: 10.1007/s11011-022-01070-w

Maple Syrup Urine Disease (MSUD) is a metabolic disorder characterized by high levels in blood and urine of branched-chain amino acids leucine, isoleucine, and valine and their alpha-ketoacids, by a partial or total blockade in the activity of branched-chain complex alpha-keto acids dehydrogenase. The main symptoms in MSUD occur in the central nervous system, including cognitive deficits, locomotor, poor feeding, seizures, psychomotor delay, and mental retardation, but the mechanisms of neurotoxicity and behavior alteration due to this disease are poorly understood, thus this study aimed at showing the effects of leucine exposure on glutamate levels and behavior in zebrafish. For this, we analyzed the behavior using the social preference test and novel object recognition test, moreover, we analyse the glutamate levels and uptake using scintillation and high-performance liquid chromatography methods. Our results demonstrated a decrease in glutamate levels and uptake, accompanied by memory and social impairment. In conclusion, these results suggest that alterations in glutamate levels can be associated with behavior impairment, however, more studies are necessary to understand the mechanisms for brain damage in MSUD.