{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:35:30Z","timestamp":1791916530221,"version":"4.3.4"},"reference-count":91,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100013209","name":"Hellenic Foundation for Research and Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013209","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Early life stress exposure exerts detrimental effects in adulthood and is a risk factor for psychiatric disorders. Studies addressing the molecular mechanisms of early life stress have primarily focused on hormones and stress circuits. However, little is known on how mitochondria and mitochondrial dynamics (i.e., the orchestration of mitochondrial fission, fusion, mitophagy, and biogenesis) modulate early life stress responses. Here, we used a maternal separation with early weaning (MSEW) paradigm to investigate the behavioral and molecular early life stress\u2010elicited effects in male and female C57BL\/6 mice in adulthood. We first applied a behavioral test battery to assess MSEW\u2010driven, anxiety\u2010related and stress\u2010coping alterations. We then looked for MSEW\u2010induced, mitochondria\u2010centered changes in cingulate cortex, hippocampus and cerebellum, as well as in plasma by combining protein, mRNA, mitochondrial DNA copy number (mtDNAcn) and metabolomics analyses. We found that MSEW mice are more anxious, show decreased antioxidant capacity in the cingulate cortex and have higher mRNA levels of the fission regulator\n                    <jats:italic>Fis1<\/jats:italic>\n                    and the mitophagy activator\n                    <jats:italic>Pink1<\/jats:italic>\n                    in the hippocampus, indicating a shift towards mitochondrial degradation. Hippocampal mRNA level alterations of apoptotic markers further suggest an MSEW\u2010driven activation of apoptosis accompanied by a dysregulation of purine catabolism in the cerebellum in MSEW mice. Sex\u2010specific analysis revealed distinct MSEW\u2010induced changes in male and female mice at the molecular level. Our work reveals a previously unexplored role of mitochondrial dynamics in regulating early life stress effects and highlights a mitochondria\u2010centered dysregulation as a persistent outcome of early life stress in adulthood.\n                  <\/jats:p>","DOI":"10.1002\/jnr.70023","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T06:48:53Z","timestamp":1744094933000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Early Life Stress Induces Brain Mitochondrial Dynamics Changes and Sex\u2010Specific Adverse Effects in Adulthood"],"prefix":"10.1002","volume":"103","author":[{"given":"Angeliki\u2010Maria","family":"Vlaikou","sequence":"first","affiliation":[{"name":"Laboratory of Biochemistry, Department of Biological Applications and Technology, School of Health Sciences University of Ioannina  Ioannina Greece"},{"name":"Biomedical Research Institute, Foundation for Research and Technology\u2010Hellas (BRI\u2010FORTH)  Ioannina Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Nussbaumer","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Department of Biological Applications and Technology, School of Health Sciences University of Ioannina  Ioannina Greece"},{"name":"Biomedical Research Institute, Foundation for Research and Technology\u2010Hellas (BRI\u2010FORTH)  Ioannina Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aikaterini","family":"Iliou","sequence":"additional","affiliation":[{"name":"Section of Pharmaceutical Chemistry, Department of Pharmacy, School of Health Sciences National and Kapodistrian University of Athens (NKUA)  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria P.","family":"Papageorgiou","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Department of Biological Applications and Technology, School of Health Sciences University of Ioannina  Ioannina Greece"},{"name":"Biomedical Research Institute, Foundation for Research and Technology\u2010Hellas (BRI\u2010FORTH)  Ioannina Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chrysoula","family":"Komini","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Department of Biological Applications and Technology, School of Health Sciences University of Ioannina  Ioannina Greece"},{"name":"Biomedical Research Institute, Foundation for Research and Technology\u2010Hellas (BRI\u2010FORTH)  Ioannina Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5468-0337","authenticated-orcid":false,"given":"Daniela","family":"Theodoridou","sequence":"additional","affiliation":[{"name":"Laboratory of Biology, Faculty of Medicine, School of Health Sciences University of Ioannina  Ioannina Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Benaki","sequence":"additional","affiliation":[{"name":"Section of Pharmaceutical Chemistry, Department of Pharmacy, School of Health Sciences National and Kapodistrian University of Athens (NKUA)  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Mikros","sequence":"additional","affiliation":[{"name":"Section of Pharmaceutical Chemistry, Department of Pharmacy, School of Health Sciences National and Kapodistrian University of Athens (NKUA)  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelos","family":"Gikas","sequence":"additional","affiliation":[{"name":"Section of Analytical Chemistry, Department of Chemistry, School of Science National and Kapodistrian University of Athens (NKUA)  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Syrrou","sequence":"additional","affiliation":[{"name":"Laboratory of Biology, Faculty of Medicine, School of Health Sciences University of Ioannina  Ioannina Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2991-4901","authenticated-orcid":false,"given":"Michaela D.","family":"Filiou","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Department of Biological Applications and Technology, School of Health Sciences University of Ioannina  Ioannina Greece"},{"name":"Biomedical Research Institute, Foundation for Research and Technology\u2010Hellas (BRI\u2010FORTH)  Ioannina Greece"},{"name":"Institute of Biosciences, University Research Center of Ioannina University of Ioannina  Ioannina Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2017.02.022"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s42000-018-0002-z"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20130234"},{"key":"e_1_2_11_5_1","article-title":"Functional Genomic and Proteomic Analysis Reveals Disruption of Myelin\u2010Related Genes and Translation in a Mouse Model of Early Life Neglect","volume":"22","author":"Bordner K. A.","year":"2011","journal-title":"Frontiers in Psychiatry"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2015.10.065"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-022-02830-6"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.4236\/jbise.2017.102007"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C400557200"},{"key":"e_1_2_11_10_1","doi-asserted-by":"crossref","DOI":"10.1002\/brb3.841","article-title":"Maternal Separation Affects Expression of Stress Response Genes and Increases Vulnerability to Ethanol Consumption","volume":"8","author":"Almeida Magalh\u00e3es \u03a4.","year":"2018","journal-title":"Brain and Behavior: A Cognitive Neuroscience Perspective"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2021.09.008"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-011-0350-9"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2022.114099"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2014.07.019"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.200900647"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo11020128"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2019.07.002"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2011.06.009"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2020.12.003"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-11-123"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2015.06.015"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci10070447"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-018-0195-5"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2020.147117"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2022.01.009"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2021.113241"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2019.04.028"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2018.00306"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1512653112"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.660095"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/10253890.2021.1973997"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002143"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2016.06.015"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2006.11.017"},{"key":"e_1_2_11_35_1","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/brb3.69","article-title":"Maternal Separation Is Associated With Strain\u2010Specific Responses to Stress and Epigenetic Alterations to Nr3c1, Avp, and Nr4a1 in Mouse","volume":"2","author":"Kember R. L.","year":"2012","journal-title":"Brain and Behavior: A Cognitive Neuroscience Perspective"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1177\/24705470211067181"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03510-6"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12710"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/10253890701821081"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/neuro.08.027.2009"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2013.00078"},{"key":"e_1_2_11_42_1","first-page":"3923","article-title":"Agarose Gel Electrophoresis for the Separation of DNA Fragments","volume":"62","author":"Lee P. Y.","year":"2012","journal-title":"Journal of Visualized Experiments"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/242709"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2007.05522.x"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_11_46_1","first-page":"2580","article-title":"Tau Deletion Prevents Stress\u2010Induced Dendritic Atrophy in Prefrontal Cortex: Role of Synaptic Mitochondria","volume":"27","author":"Lopes S.","year":"2017","journal-title":"Cerebral Cortex"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e12-10-0721"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.20600"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2014.00073"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200910140"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2015.171"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2006.05.003"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2016.08.010"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2019.100774"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200809125"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21197212"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2014.00166"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2015.341"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-010-2010-9"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020104705"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3513"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2019.00220"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00833"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2024.105837"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X21666230713094843"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep35317"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2019.112049"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.14844"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1097\/PSY.0000000000000545"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1515733112"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2008.06.005"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1177\/1367493519864742"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2021.105346"},{"key":"e_1_2_11_74_1","article-title":"Resistance to Early\u2010Life Stress in Mice: Effects of Genetic Background and Stress Duration","volume":"5","author":"Savignac H. M.","year":"2021","journal-title":"Frontiers in Behavioral Neuroscience"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094850"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2021.661993"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.04.066"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-024-04116-5"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1042\/EBC20170104"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2016.06.021"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23105333"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2443.1998.00223.x"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.202100244"},{"key":"e_1_2_11_84_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-60530-4"},{"key":"e_1_2_11_85_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0911187107"},{"key":"e_1_2_11_86_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-020-0856-0"},{"key":"e_1_2_11_87_1","doi-asserted-by":"publisher","DOI":"10.1093\/scan\/nsm018"},{"key":"e_1_2_11_88_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.01054.x"},{"key":"e_1_2_11_89_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-16183-x"},{"key":"e_1_2_11_90_1","first-page":"10812","article-title":"Early Maternal Separation Promotes Apoptosis in Dentate Gyrus and Alters Neurological Behaviors in Adolescent Rats","volume":"10","author":"Yang S.","year":"2017","journal-title":"International Journal of Clinical and Experimental Pathology"},{"key":"e_1_2_11_91_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M111.008110"},{"key":"e_1_2_11_92_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.15-274258"}],"container-title":["Journal of Neuroscience Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.70023","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T10:07:54Z","timestamp":1754906874000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jnr.70023"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":91,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/jnr.70023"],"URL":"https:\/\/doi.org\/10.1002\/jnr.70023","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/JNR.70023\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70023\/v5\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70023\/v3\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70023\/v4\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70023\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70023\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70023\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70023\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70023\/v1\/review4","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70023\/v1\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70023\/v4\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70023\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70023\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70023\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70023\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70023\/v5\/decision1","asserted-by":"object"}]},"ISSN":["0360-4012","1097-4547"],"issn-type":[{"value":"0360-4012","type":"print"},{"value":"1097-4547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"2023-04-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70023"}}