Music-performance regulates microRNAs in professional musicians

Abstract

Musical training and performance require precise integration of multisensory and motor centres of the human brain and can be regarded as an epigenetic modifier of brain functions. Numerous studies have identified structural and functional differences between the brains of musicians and non-musicians and superior cognitive functions in musicians. Recently, music-listening and performance has also been shown to affect the regulation of several genes, many of which were identified in songbird singing. MicroRNAs affect gene regulation and studying their expression may give new insights into the epigenetic effect of music. Here, we studied the effect of 2 hours of classical music-performance on the peripheral blood microRNA expressions in professional musicians with respect to a control activity without music for the same duration. As detecting transcriptomic changes in the functional human brain remains a challenge for geneticists, we used peripheral blood to study music-performance induced microRNA changes and interpreted the results in terms of potential effects on brain function, based on the current knowledge about the microRNA function in blood and brain. We identified significant (FDR <0.05) up-regulation of five microRNAs; hsa-miR-3909, hsa-miR-30d-5p, hsa-miR-92a-3p, hsa-miR-222-3p and hsa-miR-30a-5p; and down-regulation of two microRNAs; hsa-miR-6803-3p and hsa-miR-1249-3p. hsa-miR-222-3p and hsa-miR-92a-3p putatively target FOXP2, which was found down-regulated by microRNA regulation in songbird singing. miR-30d and miR-222 corroborate microRNA response observed in zebra finch song-listening/learning. miR-222 is induced by ERK cascade, which is important for memory formation, motor neuron functions and neuronal plasticity. miR-222 is also activated by FOSL1, an immediate early gene from the FOS family of transcriptional regulators which are activated by auditory-motor stimuli. miR-222 and miR-92 promote neurite outgrowth by negatively regulating the neuronal growth inhibitor, PTEN, and by activating CREB expression and phosphorylation. The up-regulation of microRNAs previously found to be regulators of auditory and nervous system functions (miR-30d, miR-92a and miR-222) is indicative of the sensory perception processes associated with music-performance. Akt signalling pathway which has roles in cell survival, cell differentiation, activation of CREB signalling and dopamine transmission was one of the functions regulated by the up-regulated microRNAs; in accordance with functions identified from songbird learning. The up-regulated microRNAs were also found to be regulators of apoptosis, suggesting repression of apoptotic mechanisms in connection with music-performance. Furthermore, comparative analyses of the target genes of differentially expressed microRNAs with that of the song-responsive microRNAs in songbirds suggest convergent regulatory mechanisms underlying auditory perception.

How far musicality and perfect pitch are derived from genetic factors?

“…It had been shown by demonstration of upregulation of microRNA fraction in peripheral blood as soon as 2 h after classical music performance. Five of the studied microRNA reached a level of significance: has-miR-3909, has-miR-30d-5p, has-miR-92a-3p, has-miR-222-3p, and has-miR-30a-5p (Nair et al 2019 ). Recently genome-wide linkage and association scanning were employed to identify genes affecting auditory and creative involvement in music.…”

Human Genomics and the Biocultural Origin of Music

“…It has been verified that, for professional musicians, a concert of two hours induces a differential expression of 73 genes, involving both upregulation (51 genes) and downregulation (22 genes) [127]. In an analogous way, listening to music determines the differential expression of several genes and microRNAs, but depending on the degree of musical education and musical aptitude [147,148]. It is interesting to note that some of the genes are regulated both after music performance and listening to music and there is also evidence that some genes are upregulated after music performance but downregulated after listening to music [147,148].…”

“…Of note, there is overlap between the results of microRNAs and those of genes differentially expressed; in particular, some of these genes are target of the miRNAs with differential expression, both regarding the conditions of music performance and listening to music. In this body of research, samples of peripheral whole blood were used, as its transcriptome is shared for more than 80% with other tissues, including the brain which is inaccessible [148][149][150][151]. It has been verified that, for professional musicians, a concert of two hours induces a differential expression of 73 genes, involving both upregulation (51 genes) and downregulation (22 genes) [127].…”

“…In an analogous way, listening to music determines the differential expression of several genes and microRNAs, but depending on the degree of musical education and musical aptitude [147,148]. It is interesting to note that some of the genes are regulated both after music performance and listening to music and there is also evidence that some genes are upregulated after music performance but downregulated after listening to music [147,148]. Both after listening to and playing music, the upregulated genes are involved in comparable functions, such as the neuronal homeostasis of dopamine, cognitive functions, neuronal plasticity, learning and memory [147,148].…”

“…It is interesting to note that some of the genes are regulated both after music performance and listening to music and there is also evidence that some genes are upregulated after music performance but downregulated after listening to music [147,148]. Both after listening to and playing music, the upregulated genes are involved in comparable functions, such as the neuronal homeostasis of dopamine, cognitive functions, neuronal plasticity, learning and memory [147,148]. On the other hand, the downregulated genes include the ones targeted by transcription regulators for proinflammatory cytokines [147] and in neuronal apoptosis [148].…”