Myelin basic protein recovery during PKU mice lifespan and the potential role of microRNAs on its regulation

• DOI: 10.1016/j.nbd.2023.106093
• Publication Date: 2023-03-21T12:18:27Z
• Authors: Alessandro Bregalda; Claudia Carducci; Maria Teresa Viscomi; Francesca Pierigè; Sara Biagiotti; Michele Menotta; Federica Biancucci; Tiziana Pascucci; Vincenzo Leuzzi; Mauro Magnani; Luigia Rossi
• Keywords: Proteomics; Cerebral plasticity; Microarray; MicroRNA; Mouse maturation; Myelin basic protein; Phenylketonuria; Cerebral plasticity; MicroRNA; Microarray; Mouse maturation; Myelin basic protein; Phenylketonuria; Longevity; Membrane Proteins; MicroRNA; Neurosciences. Biological psychiatry. Neuropsychiatry; Myelin Basic Protein; Nerve Tissue Proteins; Microarray; myelin; Myelin basic protein; Mice; MicroRNAs; Mouse maturation; Phenylketonurias; Phenylketonuria; Animals; RNA, Messenger; Cerebral plasticity; RC321-571

Untreated phenylketonuria (PKU) patients and PKU animal models show hypomyelination in the central nervous system white matter damages, which are accompanied by myelin basic protein (MBP) impairment. Despite many assumptions, primary explanation of mentioned cerebral outcomes remains elusive. In this study, MBP mRNA expression on brains wild type (WT) phenylketonuric (ENU2) mice were analyzed throughout lifespan (14-60-180-270-360-540 post-natal days, PND). The results confirmed low at first PND times, while revealed an unprecedented progressive recovery aged ENU2 mice. Unexpectedly, unaltered between WT was always observed. Additionally, for same time intervals, a significant decrease phenylalanine concentration peripheral blood brain detected, to date, time. scenario, translational hindrance during initial late development hypothesized, leading execution microRNA microarray analysis 60 brains, followed proteomic assay 360 order validate silico miRNA-target predictions. Taken together, miR-218-1-3p, miR-1231-3p miR-217-5p considered as most impactful microRNAs, since downregulation their potential targets (MAG, CNTNAP2 ANLN, respectively) can indirectly lead expression. These miRNAs, addition, follow opposite trend compared adulthood, target proteins complete normalization conclusion, these provide new perspective pathophysiology understanding possible treatment, emphasizing modulating role differentially expressed microRNAs mouse lifespan.