{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:34:14Z","timestamp":1787502854117,"version":"build-2736575974"},"reference-count":69,"publisher":"The Royal Society","issue":"5","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004099","name":"Ligue Contre le Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004099","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009879","name":"FACE Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009879","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004794","name":"Centre National de la Recherche Scientifique","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["Open Biol."],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:p>Sound sensitivity is a common sensory complaint for people with autism spectrum disorder (ASD). How and why sounds are perceived as overwhelming by affected people is unknown. To process sound information properly, the brain requires high activity and fast processing, as seen in areas like the medial nucleus of the trapezoid body (MNTB) of the auditory brainstem. Recent work has shown dysfunction in mitochondria in a genetic model of ASD, Fragile X Syndrome (FXS). Whether mitochondrial functions are also altered in sound-processing neurons has not been characterized yet. To address this question, we imaged MNTB in a mouse model of FXS. We stained MNTB brain slices from wild-type and FXS mice with two mitochondrial markers, TOMM20 and PMPCB, located on the outer mitochondrial membrane and in the matrix, respectively. Our imaging reveals significant sex-specific differences between genotypes. Colocalization analyses between TOMM20 and PMPCB show that the integrity of mitochondrial subcompartments is most disrupted in female FXS mice compared with female wild-type mice. We highlight a quantitative fluorescence microscopy pipeline to monitor mitochondrial functions in the MNTB from control or FXS mice and provide four complementary readouts, paving the way to understanding how cellular mechanisms important to sound encoding are altered in ASD.<\/jats:p>","DOI":"10.1098\/rsob.240384","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T19:05:47Z","timestamp":1747163147000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Sex-specific loss of mitochondrial membrane integrity in the auditory brainstem of a mouse model of Fragile X Syndrome"],"prefix":"10.1098","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3069-6108","authenticated-orcid":true,"given":"Claire","family":"Caron","sequence":"first","affiliation":[{"name":"CNRS IGDR (Institute of Genetics and Development of Rennes), University of Rennes, Rennes, F-35000 UMR 6290, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3779-0141","authenticated-orcid":true,"given":"Elizabeth Anne","family":"McCullagh","sequence":"additional","affiliation":[{"name":"Integrative Biology, Oklahoma State University","place":["Stillwater, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7359-5733","authenticated-orcid":true,"given":"Giulia","family":"Bertolin","sequence":"additional","affiliation":[{"name":"CNRS IGDR (Institute of Genetics and Development of Rennes), University of Rennes, Rennes, F-35000 UMR 6290, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2025,5,14]]},"reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.059055"},{"key":"e_1_3_8_3_2","doi-asserted-by":"publisher","DOI":"10.56021\/9780801868436"},{"key":"e_1_3_8_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-021-00432-0"},{"key":"e_1_3_8_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25063421"},{"key":"e_1_3_8_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-019-0338-y"},{"key":"e_1_3_8_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.07.008"},{"key":"e_1_3_8_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.702020"},{"key":"e_1_3_8_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.10.008"},{"key":"e_1_3_8_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-023-00783-1"},{"key":"e_1_3_8_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.103901"},{"key":"e_1_3_8_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature18928"},{"key":"e_1_3_8_13_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00130.2021"},{"key":"e_1_3_8_14_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1913"},{"key":"e_1_3_8_15_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20160485"},{"key":"e_1_3_8_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-002-2010-5"},{"key":"e_1_3_8_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.16091"},{"key":"e_1_3_8_18_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0363-19.2019"},{"key":"e_1_3_8_19_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2014.00116"},{"key":"e_1_3_8_20_2","first-page":"1","article-title":"Mechanisms underlying auditory processing deficits in fragile X syndrome","volume":"00","author":"McCullagh EA","year":"2020","unstructured":"McCullagh EA et al. 2020 Mechanisms underlying auditory processing deficits in fragile X syndrome. FASEB J. 00, 1\u201318. (doi:10.1096\/fj.201902435r)","journal-title":"FASEB J."},{"key":"e_1_3_8_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0117266"},{"key":"e_1_3_8_22_2","first-page":"375","article-title":"Tonotopic alterations in inhibitory input to the medial nucleus of the trapezoid body in a mouse model of Fragile X syndrome","volume":"262","author":"McCullagh EA","year":"2017","unstructured":"McCullagh EA, Salcedo E, Huntsman MM, Klug A. 2017 Tonotopic alterations in inhibitory input to the medial nucleus of the trapezoid body in a mouse model of Fragile X syndrome. J. Comp. Neurol. 262, 375. (doi:10.1002\/cne.24290)","journal-title":"J. Comp. Neurol."},{"key":"e_1_3_8_23_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0839-18.2019"},{"key":"e_1_3_8_24_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0886-19.2019"},{"key":"e_1_3_8_25_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.772943"},{"key":"e_1_3_8_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnint.2021.803483"},{"key":"e_1_3_8_27_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.987939"},{"key":"e_1_3_8_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2022.105767"},{"key":"e_1_3_8_29_2","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0300-19.2019"},{"key":"e_1_3_8_30_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2310-16.2017"},{"key":"e_1_3_8_31_2","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0264-17.2017"},{"key":"e_1_3_8_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2563"},{"key":"e_1_3_8_33_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00234"},{"key":"e_1_3_8_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2019.04.006"},{"key":"e_1_3_8_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.23520"},{"key":"e_1_3_8_36_2","article-title":"Coherent anti-stokes raman spectroscopy (cars) application for imaging myelination in brain slices","volume":"185","author":"McCullagh EA","year":"2022","unstructured":"McCullagh EA, Poleg S, Stich D, Moldovan R, Klug A. 2022 Coherent anti-stokes raman spectroscopy (cars) application for imaging myelination in brain slices. J. Vis. Exp 185, e64013. (doi:10.3791\/64013-v)","journal-title":"J. Vis. Exp"},{"key":"e_1_3_8_37_2","first-page":"23","article-title":"Fmr1 knockout mice: a model to study Fragile X mental retardation","volume":"78","author":"The Dutch-Belgian Fragile X Consorthium","year":"1994","unstructured":"The Dutch-Belgian Fragile X Consorthium. 1994 Fmr1 knockout mice: a model to study Fragile X mental retardation. Cell 78, 23\u201333.","journal-title":"Cell"},{"key":"e_1_3_8_38_2","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2022.0878"},{"key":"e_1_3_8_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2012.14"},{"key":"e_1_3_8_40_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.38111"},{"key":"e_1_3_8_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.09.034"},{"key":"e_1_3_8_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2016.12.015"},{"key":"e_1_3_8_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.20198"},{"key":"e_1_3_8_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2818.2006.01706.x"},{"key":"e_1_3_8_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2014.05.012"},{"key":"e_1_3_8_46_2","unstructured":"R Core Team. 2013 R: a language and environment for statistical computing. Vienna Austria: R foundation for statistical computing. See http:\/\/www.R-project.org\/."},{"key":"e_1_3_8_47_2","unstructured":"Wickham H. 2016 ggplot2: Elegant graphics for data analysis. New York NY: Springer-Verlag. (doi:10.1007\/978-3-319-24277-4_9)"},{"key":"e_1_3_8_48_2","doi-asserted-by":"publisher","DOI":"10.1121\/10.0024357"},{"key":"e_1_3_8_49_2","article-title":"Fitting linear mixed-effects models using lme4","author":"Bates D","year":"2014","unstructured":"Bates D, M\u00e4chler M, Bolker B, Walker S. 2014 Fitting linear mixed-effects models using lme4. arXiv. (doi:10.18637\/jss.v067.i01)","journal-title":"arXiv."},{"key":"e_1_3_8_50_2","unstructured":"Lenth RV. 2019 emmeans: Estimated marginal means aka least-squares means. See https:\/\/CRAN.R-project.org\/package=emmeans."},{"key":"e_1_3_8_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2023.03.002"},{"key":"e_1_3_8_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2013.10.015"},{"key":"e_1_3_8_53_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00272.2006"},{"key":"e_1_3_8_54_2","first-page":"209","volume-title":"Biological basis of sex differences in psychopharmacology","author":"Rinehart NJ","year":"2011","unstructured":"Rinehart NJ, Cornish KM, Tonge BJ. 2011 Gender differences in neurodevelopmental disorders: autism and Fragile X syndrome. In Biological basis of sex differences in psychopharmacology (eds JC Neill, J Kulkarni), pp. 209\u2013229, vol. 8. Berlin, Heidelberg: Springer. (doi:10.1007\/7854_2010_96)"},{"key":"e_1_3_8_55_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10863-014-9583-7"},{"key":"e_1_3_8_56_2","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13105"},{"key":"e_1_3_8_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.02.002"},{"key":"e_1_3_8_58_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr048"},{"key":"e_1_3_8_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.12.007"},{"key":"e_1_3_8_60_2","first-page":"1","article-title":"The mitophagy pathway and its implications in human diseases","volume":"8","author":"Wang S","year":"2023","unstructured":"Wang S et al. 2023 The mitophagy pathway and its implications in human diseases. Signal Transduct. Target. Ther. 8, 1\u201328. (doi:10.1038\/s41392-023-01503-7)","journal-title":"Signal Transduct. Target. Ther."},{"key":"e_1_3_8_61_2","first-page":"93","article-title":"Analyse factorielle de donn\u00e9es mixtes","volume":"52","author":"Pag\u00e8s J","year":"2004","unstructured":"Pag\u00e8s J. 2004 Analyse factorielle de donn\u00e9es mixtes. Rev. Stat. Appliqu\u00e9e 52, 93\u2013111.","journal-title":"Rev. Stat. Appliqu\u00e9e"},{"key":"e_1_3_8_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114068"},{"key":"e_1_3_8_63_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067351"},{"key":"e_1_3_8_64_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00629.2016"},{"key":"e_1_3_8_65_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00333.2021"},{"key":"e_1_3_8_66_2","doi-asserted-by":"publisher","DOI":"10.1113\/JP275107"},{"key":"e_1_3_8_67_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1125-10.2010"},{"key":"e_1_3_8_68_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0603-18.2018"},{"key":"e_1_3_8_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2023.08.021"},{"key":"e_1_3_8_70_2","unstructured":"Bertolin G. 2024 Caron et al PMPCB_TOMM20 raw images. Zenodo. (doi:10.5281\/zenodo.14274136)"}],"updated-by":[{"DOI":"10.1098\/rsob.250374","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000}}],"container-title":["Open Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rsob.240384","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/full-xml\/10.1098\/rsob.240384","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rsob.240384","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T19:05:55Z","timestamp":1747163155000},"score":1,"resource":{"primary":{"URL":"https:\/\/royalsocietypublishing.org\/doi\/10.1098\/rsob.240384"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5]]},"references-count":69,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1098\/rsob.240384"],"URL":"https:\/\/doi.org\/10.1098\/rsob.240384","relation":{"has-review":[{"id-type":"doi","id":"10.1098\/RSOB.240384\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOB.240384\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOB.240384\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOB.240384\/v1\/decision1","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.07.02.601649","asserted-by":"object"}]},"ISSN":["2046-2441"],"issn-type":[{"value":"2046-2441","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5]]},"assertion":[{"value":"2024-12-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-13","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"240384"}}