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.

Abstract	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.
Authors	Karoline Teixeira Fermo, Isabela da Silva Lemos, Hemelin Resende Farias, Marina Peyrot Rosso, Pauline Souza Effting, Guilhian Leipnitz, Emílio Luiz Streck
Journal	Metabolic brain disease (Metab Brain Dis) Vol. 38 Issue 1 Pg. 287-293 (01 2023) ISSN: 1573-7365 [Electronic] United States
PMID	36305998 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Chemical References	Amino Acids, Branched-Chain Keto Acids
Topics	Rats Animals Maple Syrup Urine Disease (metabolism) Amino Acids, Branched-Chain (metabolism) Rats, Wistar Disease Models, Animal Brain (metabolism) Keto Acids Autophagy

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