Auditory stimulation of opera music induced prolongation of murine cardiac allograft survival and maintained generation of regulatory CD4+CD25+ cells

Abstract

BackgroundInteractions between the immune response and brain functions such as olfactory, auditory, and visual sensations are likely. This study investigated the effect of sounds on alloimmune responses in a murine model of cardiac allograft transplantation.MethodsNaïve CBA mice (H2k) underwent transplantation of a C57BL/6 (B6, H2b) heart and were exposed to one of three types of music--opera (La Traviata), classical (Mozart), and New Age (Enya)--or one of six different single sound frequencies, for 7 days. Additionally, we prepared two groups of CBA recipients with tympanic membrane perforation exposed to opera for 7 days and CBA recipients exposed to opera for 7 days before transplantation (pre-treatment). An adoptive transfer study was performed to determine whether regulatory cells were generated in allograft recipients. Immunohistochemical, cell-proliferation, cytokine, and flow cytometry assessments were also performed.ResultsCBA recipients of a B6 cardiac graft that were exposed to opera music and Mozart had significantly prolonged allograft survival (median survival times [MSTs], 26.5 and 20 days, respectively), whereas those exposed to a single sound frequency (100, 500, 1000, 5000, 10,000, or 20,000 Hz) or Enya did not (MSTs, 7.5, 8, 9, 8, 7.5, 8.5 and 11 days, respectively). Untreated, CBA mice with tympanic membrane perforations and CBA recipients exposed to opera for 7 days before transplantation (pre-treatment) rejected B6 cardiac grafts acutely (MSTs, 7, 8 and 8 days, respectively). Adoptive transfer of whole splenocytes, CD4+ cells, or CD4+CD25+ cells from opera-exposed primary allograft recipients resulted in significantly prolonged allograft survival in naive secondary recipients (MSTs, 36, 68, and > 100 days, respectively). Proliferation of splenocytes, interleukin (IL)-2 and interferon (IFN)-γ production was suppressed in opera-exposed mice, and production of IL-4 and IL-10 from opera-exposed transplant recipients increased compared to that from splenocytes of untreated recipients. Flow cytometry studies showed an increased CD4+CD25+ Forkhead box P3 (Foxp3)+ cell population in splenocytes from those mice.ConclusionOur findings indicate that exposure to opera music, such as La traviata, could affect such aspects of the peripheral immune response as generation of regulatory CD4+CD25+ cells and up-regulation of anti-inflammatory cytokines, resulting in prolonged allograft survival.

The effects of auditory enrichment on zebrafish behavior and physiology

“…Furthermore, specific type of auditory enrichment used here also affected the immune genes expression in zebrafish vs. unexposed controls ( Fig. 3A ), similar to music effects reported earlier in rodents ( Lu et al, 2010 ; Uchiyama et al, 2012 ). Here, fish exposed to auditory enrichment showed lower expression of some pro-inflammatory genes (IL-1β and IFN-γ), but without affecting anti-inflammatory genes IL-10 and IL-4 ( Fig.…”

“…The zebrafish (Danio rerio) is a widely used animal model organism in neuroscience research ( Papoutsoglou et al, 2007 ; Sicca et al, 2016 ; Levitas-Djerbi & Appelbaum, 2017 ; Uchiyama et al, 2012 ; Kalueff et al, 2013 ). They are genetically and physiologically similar to others vertebrates, such as rodents and humans ( Howe et al, 2013 ), and possess a well-described behavioral repertoire ( Kalueff et al, 2013 ) and stress neuroendocrine axis ( Stewart et al, 2014 ; Kalueff, Stewart & Gerlai, 2014 ; Alsop & Vijayan, 2009 ).…”

Music Affects Rodents: A Systematic Review of Experimental Research

“…Moreover, several experimental studies in healthy rodents and in rodent disease models found similar effects as reported in humans, such as enhanced spatial ability (Xing et al, 2016c), improved neuroplasticity (Kirste et al, 2015), anxiety reduction (Escribano et al, 2014), blood pressure lowering (Sutoo and Akiyama, 2004), and increasing immune function (Uchiyama et al, 2012; Gao et al, 2016).…”

Graft protective effect and induction of CD4+Foxp3+ cell by Thrombomodulin on allograft arteriosclerosis in mice

“…Moreover, in another study, it was shown to alleviate GVHD via increasing splenic regulatory T cell [ 16 ]. Based on our previous data, it can be reasoned that inducible CD4 + Foxp3 + Treg do not disappear in a short period of time [ 17 , 18 ]. From the findings in this study that demonstrate that the general structure of the allograft was maintained even three weeks after termination of TM administration, it can be concluded that TM may generate CD4 + Foxp3 + regulatory T cells that infiltrate transplanted cardiac allografts and that greater aggregation of these cells around coronary arteries may lead to the prolongation of allograft survival.…”