Music-performance regulates microRNAs in professional musicians

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 (FDRPeer reviewe

Music-listening regulates human microRNA expression

Music-listening and performance have been shown to affect human gene expression. In order to further elucidate the biological basis of the effects of music on the human body, we studied the effects of music-listening on gene regulation by sequencing microRNAs of the listeners (Music Group) and their controls (Control Group) without music exposure. We identified upregulation of six microRNAs (hsa-miR-132-3p, hsa-miR-361-5p, hsa-miR-421, hsa-miR-23a-3p, hsa-miR-23b-3p, hsa-miR-25-3p) and downregulation of two microRNAs (hsa-miR-378a-3p, hsa-miR-16-2-3p) in Music Group with high musical aptitude. Some upregulated microRNAs were reported to be responsive to neuronal activity (miR-132, miR-23a, miR-23b) and modulators of neuronal plasticity, CNS myelination, and cognitive functions like long-term potentiation and memory. miR-132 plays a critical role in regulating TAU protein levels and is important for preventing tau protein aggregation that causes Alzheimer's disease. miR-132 andDICER, upregulated after music-listening, protect dopaminergic neurons and are important for retaining striatal dopamine levels. Some of the transcriptional regulators (FOS, CREB1, JUN, EGR1,andBDNF) of the upregulated microRNAs were immediate early genes and top candidates associated with musical traits.BDNFand SNCA, co-expressed and upregulated in music-listening and music-performance, are both are activated by GATA2, which is associated with musical aptitude. Several miRNAs were associated with song-learning, singing, and seasonal plasticity networks in songbirds. We did not detect any significant changes in microRNA expressions associated with music education or low musical aptitude. Our data thereby show the importance of inherent musical aptitude for music appreciation and for eliciting the human microRNA response to music-listening.Peer reviewe

The effect of music performance on the transcriptome of professional musicians

Music performance by professional musicians involves a wide-spectrum of cognitive and multi-sensory motor skills, whose biological basis is unknown. Several neuroscientific studies have demonstrated that the brains of professional musicians and non-musicians differ structurally and functionally and that musical training enhances cognition. However, the molecules and molecular mechanisms involved in music performance remain largely unexplored. Here, we investigated the effect of music performance on the genome-wide peripheral blood transcriptome of professional musicians by analyzing the transcriptional responses after a 2-hr concert performance and after a 'music-free' control session. The up-regulated genes were found to affect dopaminergic neurotransmission, motor behavior, neuronal plasticity, and neurocognitive functions including learning and memory. Particularly, candidate genes such as SNCA, FOS and DUSP1 that are involved in song perception and production in songbirds, were identified, suggesting an evolutionary conservation in biological processes related to sound perception/production. Additionally, modulation of genes related to calcium ion homeostasis, iron ion homeostasis, glutathione metabolism, and several neuropsychiatric and neurodegenerative diseases implied that music performance may affect the biological pathways that are otherwise essential for the proper maintenance of neuronal function and survival. For the first time, this study provides evidence for the candidate genes and molecular mechanisms underlying music performance.Peer reviewe

The effect of listening to music on human transcriptome

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Maine Campus October 03 1978

X-linked intellectual disability (XLID) is a group of genetically heterogeneous disorders characterized by substantial impairment in cognitive abilities, social and behavioral adaptive skills. Next generation sequencing technologies have become a powerful approach for identifying molecular gene mutations relevant for diagnosis.Methods & objectives: Enrichment of X-chromosome specific exons and massively parallel sequencing was performed for identifying the causative mutations in 14 Finnish families, each of them having several males affected with intellectual disability of unknown cause.status: publishe

X-exome sequencing in Finnish families with Intellectual Disability - four novel mutations and two novel syndromic phenotypes

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Variants in CUL4B are Associated with Cerebral Malformations

Variants in cullin 4B (CUL4B) are a known cause of syndromic X-linked intellectual disability. Here, we describe an additional 25 patients from 11 families with variants in CUL4B. We identified nine different novel variants in these families and confirmed the pathogenicity of all nontruncating variants. Neuroimaging data, available for 15 patients, showed the presence of cerebral malformations in ten patients. The cerebral anomalies comprised malformations of cortical development (MCD), ventriculomegaly, and diminished white matter volume. The phenotypic heterogeneity of the cerebral malformations might result from the involvement of CUL-4B in various cellular pathways essential for normal brain development. Accordingly, we show that CUL-4B interacts with WDR62, a protein in which variants were previously identified in patients with microcephaly and a wide range of MCD. This interaction might contribute to the development of cerebral malformations in patients with variants in CUL4B

Phenotypic spectrum associated with a CRADD founder variant underlying frontotemporal predominant pachygyria in the Finnish population

Intellectual disability (ID), megalencephaly, frontal predominant pachygyria, and seizures, previously called “thin” lissencephaly, are reported to be caused by recessive variants in CRADD. Among five families of different ethnicities identified, one homozygous missense variant, c.509G>A p.(Arg170His), was of Finnish ancestry. Here we report on the phenotypic variability associated for this potential CRADD founder variant in 22 Finnish individuals. Exome sequencing was used to identify candidate genes in Finnish patients presenting with ID. Targeted Sanger sequencing and restriction enzyme analysis were applied to screen for the c.509G>A CRADD variant in cohorts from Finland. Detailed phenotyping and genealogical studies were performed. Twenty two patients were identified with the c.509G>A p.(Arg170His) homozygous variant in CRADD. The majority of the ancestors originated from Northeastern Finland indicating a founder effect. The hallmark of the disease is frontotemporal predominant pachygyria with mild cortical thickening. All patients show ID of variable severity. Aggressive behavior was found in nearly half of the patients, EEG abnormalities in five patients and megalencephaly in three patients. This study provides detailed data about the phenotypic spectrum of patients with lissencephaly due to a CRADD variant that affects function. High inter- and intrafamilial phenotypic heterogeneity was identified in patients with pachygyria caused by the homozygous CRADD founder variant. The phenotype variability suggests that additional genetic and/or environmental factors play a role in the clinical presentation. Since frontotemporal pachygyria is the hallmark of the disease, brain imaging studies are essential to support the molecular diagnosis for individuals with ID and a CRADD variant.SCOPUS: ar.jinfo:eu-repo/semantics/publishe