Branched-chain amino acids (BCAA) administration increases autophagy and the autophagic pathway in brain tissue of rats submitted to a Maple Syrup Urine Disease (MSUD) protocol

• Published in: Metabolic brain disease Vol. 38; no. 1; pp. 287 - 293
• Main Authors: Fermo, Karoline Teixeira, da Silva Lemos, Isabela, Farias, Hemelin Resende, Rosso, Marina Peyrot, Effting, Pauline Souza, Leipnitz, Guilhian, Streck, Emílio Luiz
• Format: Journal Article
• Language: English
• Published: New York Springer US 2023; Springer Nature B.V
• Subjects: Amino acids; Amino Acids, Branched-Chain - metabolism; Animal models; Animal tissues; Animals; Autophagy; Bioaccumulation; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain; Brain - metabolism; Cell death; Cerebral cortex; Chain branching; Chains; Disease Models, Animal; Homeostasis; Inborn errors of metabolism; Keto Acids; Maple syrup; Maple syrup urine disease; Maple Syrup Urine Disease - metabolism; Metabolic Diseases; Neostriatum; Neurology; Neurosciences; Oncology; Original Article; Oxidative stress; Rats; Rats, Wistar; Reactive oxygen species; Syrup; Maple syrup urine disease; Oxidative stress; Branched-chain amino acids; Autophagy
• ISSN: 0885-7490; 1573-7365
• DOI: 10.1007/s11011-022-01109-y

Maple Syrup Urine Disease (MSUD) is an inborn error of metabolism (EIM) biochemically characterized by the tissue accumulation of branched-chain amino acids (BCAA) and their branched-chain alpha-keto acids. The mechanisms by which BCAA and their branched-chain alpha-keto acids lead to the neurological damage observed in MSUD are poorly understood. Mounting evidence has demonstrated that BCAA induce the overproduction of reactive oxygen species, which may modulate several important signaling pathways necessary for cellular homeostasis maintenance, such as autophagy. Taking this into account, we evaluated the effects of BCAA on the autophagic pathway in brain structures of rats submitted to the administration of these amino acids (animal model of MSUD). Our findings showed that BCAA significantly increased the levels of Beclin-1, ATG7, and ATG5 in the cerebral cortex of rats. In addition, BCAA augmented ATG12 levels in the striatum and ATG5 and LC3 I-II in the hippocampus. Therefore, our work demonstrates that the administration of BCAA increases autophagy and autophagic cell death, possibly mediated by the elevated levels of reactive species generated by BCAA.