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This process links neurotransmitter imbalance with mitochondrial oxidative stress; however, the spatiotemporal dynamics of mitochondrial MAO-A activity in vivo remain poorly understood due to the lack of effective imaging tools. Herein, we report a mitochondria-targeted small-molecule fluorescent probe, BAT, for real-time imaging of MAO-A activity in living systems. BAT integrates a propylamine recognition unit with a 2\u2032-hydroxychalcone fluorophore featuring aggregation-induced emission (AIE) and excited-state intramolecular proton transfer (ESIPT), enabling low-background fluorescence activation upon MAO-A-catalyzed oxidative deamination. BAT enables sensitive visualization of MAO-A activity in SH-SY5Y cells, primary neurons, and mouse brains. In vivo imaging further reveals elevated MAO-A activity accompanied by increased H2O2 levels in stress-susceptible mice, highlighting mitochondrial oxidative stress associated with MAO-A dysregulation. Collectively, this work provides a robust chemical imaging tool for investigating MAO-A-related pathological process.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c03441","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:01:53Z","timestamp":1789477313000},"page":"28229-28237","source":"Crossref","is-referenced-by-count":0,"title":["A Mitochondria-Targeted\nAIE-ESIPT Fluorescent Probe\nfor Imaging Monoamine Oxidase A Dynamics in Depression Models"],"prefix":"10.1021","volume":"98","author":[{"given":"Xin","family":"Wang","sequence":"first","affiliation":[{"name":"Shandong Normal University , , ,","place":["Jinan, People\u2019s Republic of China, 250014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozhe","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shandong Normal University , , ,","place":["Jinan, People\u2019s Republic of China, 250014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shandong Normal University , , ,","place":["Jinan, People\u2019s Republic of China, 250014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Ding","sequence":"additional","affiliation":[{"name":"Shandong Normal University , , ,","place":["Jinan, People\u2019s Republic of China, 250014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feida","family":"Che","sequence":"additional","affiliation":[{"name":"Shandong Normal University , , ,","place":["Jinan, People\u2019s Republic of China, 250014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shandong Normal University , , ,","place":["Jinan, People\u2019s Republic of China, 250014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhen","family":"Li","sequence":"additional","affiliation":[{"name":"Northwest Normal University , , ,","place":["Lanzhou, People\u2019s Republic China, 730070"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2356-0962","authenticated-orcid":true,"given":"Ping","family":"Li","sequence":"additional","affiliation":[{"name":"Shandong Normal University , , ,","place":["Jinan, People\u2019s Republic of China, 250014"]},{"name":"Northwest Normal University , , ,","place":["Lanzhou, People\u2019s Republic China, 730070"]},{"name":"Shandong University of Traditional Chinese Medicine , 655 Daxue Road , ,","place":["Jinan, People\u2019s Republic China, 250355"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"2026092909091790200_cit1","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/s41392-024-01738-y","article-title":"Major depressive\ndisorder: hypothesis, mechanism, prevention and treatment","volume":"9","author":"Cui","year":"2024","journal-title":"Signal Transduct. 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Neurobiol."},{"key":"2026092909091790200_cit5","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1038\/281692a0","article-title":"Differences\nin A and B forms of monoamine oxidase revealed\nby limited proteolysis and peptide mapping","volume":"281","author":"Cawthon","year":"1979","journal-title":"Nature"},{"key":"2026092909091790200_cit6","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/j.biopsych.2018.09.031","article-title":"The Impact\nof Stress and Major Depressive\nDisorder on Hippocampal and Medial Prefrontal Cortex Morphology","volume":"85","author":"Belleau","year":"2019","journal-title":"Biol. 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Soc."},{"key":"2026092909091790200_cit10","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1006\/abio.1996.0041","article-title":"Direct continuous\nfluorometric assay\nfor monoamine oxidase B","volume":"234","author":"Zhou","year":"1996","journal-title":"Anal. Biochem."},{"key":"2026092909091790200_cit11","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1006\/abio.1997.2392","article-title":"A one-step fluorometric method for\nthe continuous measurement\nof monoamine oxidase activity","volume":"253","author":"Zhou","year":"1997","journal-title":"Anal. Biochem."},{"key":"2026092909091790200_cit12","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1021\/acs.accounts.5b00512","article-title":"Two-Photon Small Molecule\nEnzymatic Probes","volume":"49","author":"Qian","year":"2016","journal-title":"Acc. Chem. 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Biol."},{"key":"2026092909091790200_cit21","doi-asserted-by":"publisher","first-page":"1907","DOI":"10.1038\/s41418-019-0470-y","article-title":"Mitochondrial\n4-HNE derived from MAO-A promotes mitoCa2+ overload in\nchronic postischemic cardiac remodeling","volume":"27","author":"Santin","year":"2020","journal-title":"Cell\nDeath Differ."},{"key":"2026092909091790200_cit22","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.jad.2017.12.073","article-title":"Chronic corticosterone-induced\ndepression mediates premature aging\nin rats","volume":"229","author":"Xie","year":"2018","journal-title":"J. Affect. Disord."},{"key":"2026092909091790200_cit23","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.1007\/s11011-024-01393-w","article-title":"hypothalamic-pituitary-adrenal axis,\nhypothalamic-pituitary-gonadal\naxis, and aggression","volume":"39","author":"Mbiydzenyuy","year":"2024","journal-title":"Metab. Brain Dis."},{"key":"2026092909091790200_cit24","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.psyneuen.2016.11.031","article-title":"Oxidative stress, inflammation and\ntreatment response\nin major depression","volume":"76","author":"Lindqvist","year":"2017","journal-title":"Psychoneuroendocrino"},{"key":"2026092909091790200_cit25","doi-asserted-by":"publisher","first-page":"2061","DOI":"10.1021\/jacs.8b11414","article-title":"Observation\nof Acetylcholinesterase in Stress-Induced Depression Phenotypes by\nTwo-Photon Fluorescence Imaging in the Mouse Brain","volume":"141","author":"Wang","year":"2019","journal-title":"J. Am. Chem. Soc."},{"key":"2026092909091790200_cit26","doi-asserted-by":"publisher","first-page":"20735","DOI":"10.1021\/jacs.0c09576","article-title":"Oxidative Damage of Tryptophan Hydroxylase-2\nMediated by Peroxisomal Superoxide Anion Radical in Brains of Mouse\nwith Depression","volume":"142","author":"Ding","year":"2020","journal-title":"J. Am. Chem. Soc."},{"key":"2026092909091790200_cit27","doi-asserted-by":"publisher","first-page":"4674","DOI":"10.1002\/anie.201901318","article-title":"Illuminating\nthe Function of the Hydroxyl Radical in the Brains of Mice with Depression\nPhenotypes by Two-Photon Fluorescence Imaging","volume":"58","author":"Wang","year":"2019","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026092909091790200_cit28","doi-asserted-by":"publisher","first-page":"11239","DOI":"10.1021\/jacs.4c18046","article-title":"Restoring\nthe Redox and Norepinephrine Homeostasis in Mouse Brains Promotes\nan Antidepressant Response","volume":"147","author":"Ding","year":"2025","journal-title":"J. Am. Chem. Soc."},{"key":"2026092909091790200_cit29","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.3390\/life12101645","article-title":"Serotonin\nType 3 Receptor Is Potentially Involved in Cellular Stress Induced\nby Hydrogen Peroxide","volume":"12","author":"Correia","year":"2022","journal-title":"Life"},{"key":"2026092909091790200_cit30","doi-asserted-by":"publisher","first-page":"10241","DOI":"10.1039\/D4TB01828A","article-title":"A versatile fluorescent probe for\nhydrogen peroxide in serotonergic neurons of living brains of mice\nwith depression","volume":"12","author":"Che","year":"2024","journal-title":"J. Mater. Chem. B"},{"key":"2026092909091790200_cit31","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1126\/science.3875898","article-title":"Distinct\nMonoamine Oxidase A and B Populations in Primate Brain","volume":"230","author":"Westlund","year":"1985","journal-title":"Science"},{"key":"2026092909091790200_cit32","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/s0896-6273(00)80048-3","article-title":"Lack of Barrels in\nthe Somatosensory\nCortex of Monoamine Oxidase A-Deficient Mice: Role of a Serotonin\nExcess during the Critical Period","volume":"16","author":"Cases","year":"1996","journal-title":"Neuron"},{"key":"2026092909091790200_cit33","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1001\/archpsyc.63.11.1209","article-title":"Elevated Monoamine\nOxidase A Levels\nin the Brain: An Explanation for the Monoamine Imbalance of Major\nDepression","volume":"63","author":"Meyer","year":"2006","journal-title":"Arch. Gen. Psychiatry"},{"key":"2026092909091790200_cit34","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1001\/archgenpsychiatry.2009.156","article-title":"Brain monoamine oxidase A binding in major depressive disorder: relationship\nto selective serotonin reuptake inhibitor treatment, recovery, and\nrecurrence","volume":"66","author":"Meyer","year":"2009","journal-title":"Arch. Gen. Psychiatry"},{"key":"2026092909091790200_cit35","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1038\/npp.2013.297","article-title":"Elevated Monoamine Oxidase A Binding\nDuring Major Depressive Episodes Is Associated with Greater Severity\nand Reversed Neurovegetative Symptoms","volume":"39","author":"Chiuccariello","year":"2014","journal-title":"Neuropsychopharmacol"}],"container-title":["Analytical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.analchem.6c03441","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/38\/28229\/68510342\/acs.analchem.6c03441.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/38\/28229\/68510342\/acs.analchem.6c03441.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:28:24Z","timestamp":1790688504000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancham\/article\/98\/38\/28229\/5429931\/A-Mitochondria-Targeted-AIE-ESIPT-Fluorescent"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":35,"journal-issue":{"issue":"38","published-online":{"date-parts":[[2026,9,15]]},"published-print":{"date-parts":[[2026,9,29]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.analchem.6c03441","relation":{},"ISSN":["0003-2700","1520-6882"],"issn-type":[{"value":"0003-2700","type":"print"},{"value":"1520-6882","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]}}}