Music elicits different gene expression responses in the buccal cavity of age-related cognitive disorders patients and healthy controls

Gomez-Carballa, A.; Navarro, L.; Mallah, N. E. Z.; Bello, X.; Pischedda, S.; Viz-Lasheras, S.; Curras, M. J.; Ferreiros-Vidal, I.; Mallah, N.; Montoto-Louzao, J.; Camino-Mera, A.; Castelo-Martinez, L.; Rey-Vazquez, S.; Redondo, L.; Dacosta-Urbieta, A.; Rivero-Calle, I.; Rodriguez-Tenreiro, C.; Martinon-Torres, F.; Salas, A.

doi:10.1101/2024.05.29.596389

bioRxiv · 10.1101/2024.05.29.596389

Music elicits different gene expression responses in the buccal cavity of age-related cognitive disorders patients and healthy controls

Gomez-Carballa, A.·Navarro, L.·Mallah, N. E. Z.·Bello, X.·Pischedda, S.·Viz-Lasheras, S.·Curras, M. J.·Ferreiros-Vidal, I.·Mallah, N.·Montoto-Louzao, J.·Camino-Mera, A.·Castelo-Martinez, L.·Rey-Vazquez, S.·Redondo, L.·Dacosta-Urbieta, A.·Rivero-Calle, I.·Rodriguez-Tenreiro, C.·Martinon-Torres, F.·Salas, A.

View original source ↗Export metadata ↓

Abstract

Recent evidence suggests that external stimuli can shape transcriptomes (sensogenomics). Specifically, the analysis of capillary blood samples has shown that musical stimuli can modulate gene expression patterns, in healthy individuals but also in those with age-related cognitive disorders (ACD), based on. Here, we present groundbreaking evidence indicating that brief exposure to music can also impact the salivary transcriptome in both healthy donors and ACD patients. Our findings reveal that music has a more pronounced effect on patients compared to controls, inducing global gene expression changes towards upregulation in ACD patients but downregulation in controls. The most significantly dysregulated genes in ACD patients include LGALS3 (downregulated) and CXCL8 (upregulated), whereas in controls, THOP1 was the top significant gene (downregulated). These genes play important roles in normal brain functions and are also altered in neurodegenerative conditions. Weighted Gene Co-expression Network Analysis reveals relevant and significant modules, both positive and negative correlated with music, implicated in neurodegenerative (e.g. autophagy) and immunological processes (e.g. IL-1, MHC). This sheds light on the complex interplay between music and molecular responses in the human body. This study underscores the potential of musical stimuli to influence gene expression patterns outside of systemic circulation, paving the way for further exploration of musics therapeutic effects. Sensogenomics Working GroupAntonio Salas Ellacuriaga - PI; Federico Martinon-Torres - PI; Laura Navarro Ramon - Coordinator GenPoB/GenVip - Instituto de Investigacion Sanitaria (IDIS) (alphabetic order)Alba Camino Mera, Albert Padin Villar, Alberto Gomez Carballa, Alejandro Perez Lopez, Alicia Carballal Fernandez, Ana Cotovad Bellas, Ana Isabel Dacosta Urbieta, Narmeen Mallah, Ana Maria Pastoriza Mourelle, Ana Maria Senin Ferreiro, Andres Muy Perez, Antia Rivas Oural, Antonio Justicia Grande, Antonio Pineiro Garcia, Anxela Cristina Delgado Garcia, Belen Mosquera Perez, Blanca Diaz Esteban, Carlos Duran Suarez, Carmen Curros Novo, Carmen Gomez Vieites, Carmen Rodriguez-Tenreiro Sanchez, Celia Varela Pajaro, Claudia Navarro Gonzalo, Cristina Seren Trasorras, Cristina Talavero Gonzalez, Eines Monteagudo Vilavedra, Estefania Rey Campos, Esther Montero Campos, Fernando Alvez Gonzalez, Fernando Caamano Vinas, Francisco Garcia Iglesias, Gloria Viz Rodriguez, Hugo Alberto Tovar Velasco, Irene Alvarez Rodriguez, Irene Garcia Zuazola, Irene Rivero Calle, Iria Afonso Carrasco, Isabel Ferreiros Vidal, Isabel Lista Garcia, Isabel Rego Lijo, Ivan Prieto Gomez, Ivan Quintana Cepedal, Jacobo Pardo Seco, Jesus Eiris Punal, Jose Gomez Rial, Jose Manuel Fernandez Garcia, Jose Maria Martinon Martinez, Julia Cela Mosquera, Julia Garcia Curras, Julian Montoto Louzao, Lara Martinez Martinez, Laura Navarro Marron, Lidia Pineiro Rodriguez, Lorenzo Redondo Collazo, Lua Castelo Martinez, Lucia Company Arciniegas, Luis Crego Rodriguez, Luisa Garcia Vicente, Manuel Vazquez Donsion, Maria Dolores Martinez Garcia, Maria Elena Gamborino Carames, Maria Elena Sobrino Fernandez, Maria Jose Curras Tuala, Maria Martinez Leis, Maria Soledad Vilas Iglesias, Maria Sol Rodriguez Calvo, Maria Teresa Autran Garcia, Marina Casas Perez, Marta Aldonza Torres, Marta Bouzon Alejandro, Marta Lendoiro Fuentes, Miriam Ben Garcia, Miriam Cebey Lopez, Montserrat Lopez Franco, Nour El Zahraa Mallah, Narmeen Mallah, Natalia Garcia Sanchez, Natalia Vieito Perez, Patricia Regueiro Casuso, Ricardo Suarez Camacho, Rita Garcia Fernandez, Rita Varela Estevez, Rosaura Picans Leis, Ruth Barral Arca, Sandra Carnota Antonio, Sandra Viz Lasheras, Sara Pischedda, Sara Rey Vazquez, Sonia Marcos Alonso, Sonia Seren Fernandez, Susana Rey Garcia, Vanesa Alvarez Iglesias, Victoria Redondo Cervantes, Vanesa Alvarez Iglesias, Wiktor Dominik Nowak, Xabier Bello Paderne, Xabier Mazaira Lopez Nursing volunteers (alphabetic order)Alejandra Fernandez Mendez, Ana Isabel Abadin Campana, Ana Maria Leon Caamano, Ana Maria Buide Illobre, Angeles Mera Cores, Carmen Nieves Vastro, Carolina Suarez Crego, Concepcion Rey Iglesias, Cristina Candal Regueira, Dolores Barreiro Puente, Elvira Rodriguez Rodriguez, Eugenia Gonzalez Budino, Eva Rey Alvarez, Fernando Rodriguez Gerpe, Gemma Albela Silva, Isabel Castro Perez, Isabel Dominguez Rios, Jose Angel Fernandez de la Iglesia, Jose Cruces Vazquez, Jose Luis Cambeiro Quintela, Jose Ramon Magarinos Iglesias, Julia Rey Brandariz, Julio Abel Fernandez Lopez, Luisa Garcia Vicente, Manuel Gonzalez Lito, Manuel Gonzalez Lijo, Manuela Perez Rivas, Margarita Turnes Paredes, Maria Aurora Mendez Lopez, Maria Begona Tome Arufe, Maria Campos Torres, Maria del Carmen Baloira Nogueira, Maria del Carmen Garcia juan, Maria Esther Moricosa Garcia, Maria Luz Chao Jarel, Maria Martinez Leis, Maria Mercedes Jimenez Santos, Maria Salome Buide Illobre, Maria Victoria Lopez Pereira, Mercedes Jorge Gonzalez, Mercedes Isolina Rodriguez Rodriguez, Miren Payo Puente, Natalia Carter Dominguez, Olga Maria Reyes Gonzalez, Pilar Mera Rodriguez, Purificacion Sebio Brandariz, Salome Quintans lago, Yolanda Rodriguez Taboada, Maria Pereira Grau. Other volunteers (alphabetic order)Alba Arias Gomez, Alejandro Moreno Diaz, Ana Arca Maran, Astro Gonzalez Guirado, Brais Garcia Iglesias, Carlos Sanchez Rubin, Carmen Otero de Andres, Clara Perez Errazquin Barrera, Claudia Rey Posse, Cristina Rojas Garcia, Eduardo Xavier Gimenez Bargiela, Elena Gloria Morales Garcia, Fabio Izquierdo Garcia Escribano, Gabriel Guisande Garcia, Jaime Lopez Martin, Lara Pais Ramiro, Lucia Rico Montero, Luis Estevez Martinez, Manuel Estevez Casal, Maria Aranzazu Palomino Cano, Maria Rubio Valdes, Marisol Nogales Benitez, Miryam Tilve Perez, Nuria Villar Muinos, Pablo Del Cerro Rodriguez, Pablo Pozuelo Martinez Cardenoso, Salma Ouahabi El Ouahabi, Santiago Vazquez Calvache

Explore related subjects

genomics Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Gomez-Carballa, A., Navarro, L., Mallah, N. E. Z., Bello, X., Pischedda, S., Viz-Lasheras, S., Curras, M. J., Ferreiros-Vidal, I., Mallah, N., Montoto-Louzao, J., Camino-Mera, A., Castelo-Martinez, L., Rey-Vazquez, S., Redondo, L., Dacosta-Urbieta, A., Rivero-Calle, I., Rodriguez-Tenreiro, C., Martinon-Torres, F., Salas, A.. 2024-06-02. Music elicits different gene expression responses in the buccal cavity of age-related cognitive disorders patients and healthy controls. https://doi.org/10.1101/2024.05.29.596389

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Sequence and epigenetic characterization of chromosome 21 centromeres in a family with recurrent Trisomy 21

Trisomy 21 (T21) is the most common genetic cause of intellectual disability, yet the molecular mechanisms underlying maternal meiosis I errors--responsible for ~70% of free T21 cases--remain poorly understood. In this preliminary study, we used long-read sequencing and genome assembly to investigate the DNA sequence and epigenetic features of chromosome 21 (chr21) centromeres in a family with recurrent free T21 due to maternal meiosis I errors. The mother, who had two affected and three unaffected children, showed no mosaicism or structural rearrangements. One of her two chr21 centromeres lacked a pronounced centromere dip region (CDR), displaying instead a diffuse hypomethylation pattern (dCDR) with much higher methylated CpG levels (55%) compared to its homologue (36%). This dCDR was transmitted to an unaffected child and the affected proband analyzed, suggesting it was present in one of the maternal chr21 since she was at least 32 years of age. Chr21 dCDRs were not observed in seven young mothers with children with T21 or previously described in the literature in 108 population haplotypes. We hypothesize that dCDRs may weaken kinetochore function, increasing nondisjunction risk, and propose two models linking such epigenetic variation to maternal age-related T21 risk. These findings highlight the value of complete centromere characterization in families with children with T21 and suggest centromere methylation status of chr21 as a potential T21 risk factor for future investigation.

genomics↗

bioRxiv2026

Single-Cell Analytics for Dose Response (SCADR) discriminates PTEN missense variants by lipid and protein phosphatase dysfunction

The proliferation of sequencing efforts has revealed a vast and expanding catalog of single nucleotide gene variants, many associated to, but with unclear roles in disease. Fully charactering variant impacts and linking specific protein dysfunctions to disease are challenging due to the multi-functional nature of many proteins and varying degree of variant effects on these functions. Lagging are sensitive approaches to empirically assess the impact of missense variant-induced single amino acid changes on a wide range of protein functions. To address these issues, we have developed an open-source computational analysis tool called SCADR (Single-Cell Analytics for Dose Response) for simultaneously measuring and comparing impacts of exogenously-expressed variants on multiple signaling pathways using multiplex phospho-antibody spectral flow cytometry in human cell lines. SCADR retains and correlates single-cell measures of signal protein activity states along with expression levels of exogenously-expressed variants, providing rich characterization of multiple protein functions, signaling protein interactions, and enhanced discrimination of variant impacts on different signaling pathways, highlighting each variants unique dysfunction profile. Here, we apply SCADR for analyses of the impact of 6 variants of the tumor-suppressor protein PTEN (P38H, C124S, G129E, Y138L, D268E, 4A) expressed in HEK293 cells on the phosphorylation states of the canonical and noncanonical downstream signaling proteins Akt, S6, CREB, ERK, and p38 detected with fluorophore-conjugated phospho-antibodies, along with an antibody detecting an N-terminal HA tag on PTEN variants allowing measures of dose-response effects of each variants expression on signaling cascades. Results identify variant-specific impacts on downstream signaling cascades.

genomics↗

bioRxiv2026

Microsecond molecular dynamics of SOD1 variants suggest a structural basis for divergent ALS clinical outcomes

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by progressive motor neuron degeneration. Mutations in the SOD1 gene represent the second most common genetic cause of ALS (ALS), and distinct SOD1 missense variants present with markedly different clinical profiles. A4V leads to an aggressive form of the disease (median survival [~]1y), H46R confers a mild, slowly progressive course and I113T exhibits an intermediate phenotype. The molecular basis by which these mutations produce divergent clinical outcomes remains poorly understood. We performed extensive classical molecular dynamics simulations of wild-type SOD1 and the three ALS-associated variants in the apo monomeric state to attempt to investigate the mechanisms behind such phenotypic differences. Structural stability, global compactness, and conformational flexibility, as well as analysis of collective motions between residues and estimation of free energy, were assessed. The H46R, A4V, and I113T variants exhibited distinct dynamic behaviours, highlighting differences in structural stability, local flexibility, and intramolecular interactions. These findings suggest that specific structural regions may contribute differently to protein dysfunction and could represent key elements for understanding the relationship between molecular dynamic properties and the differing clinical severity associated with these variants. Most strikingly, H46R exhibited exceptional structural stability across every analytical level, the lowest global deviation, most attenuated local flexibility, strongest internal dynamic coordination, and the deepest, most confined free energy basins of any system examined. This convergent multi-layered evidence of structural restraint provides a compelling mechanistic basis for the mild and slowly progressive clinical course of H46R ALS, suggesting that enhanced conformational rigidity, rather than bulk destabilisation, is the defining biophysical feature of this variant, and that its pathogenic mechanism operates through a route fundamentally decoupled from the aggregation-driven toxicity that characterises the more aggressive SOD1-ALS mutations.

genomics↗