{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:35:06Z","timestamp":1785198906401,"version":"3.55.0"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T00:00:00Z","timestamp":1613088000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T00:00:00Z","timestamp":1613088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Psychiatry"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We mimicked mild mitochondrial-distress robustly reported in bipolar-disorder (BD) by chronic exposure to uniquely low doses of inhibitors of mitochondrial-respiration complexes in vitro and in vivo. Exposure of the neuronal-originating SH-SY5Y cells to very low dose (10\u2009pM) rotenone, a mitochondrial-respiration complex (Co)I inhibitor, for 72 or 96\u2009h did not affect cell viability and reactive oxygen species (ROS) levels. Yet, it induced a dual effect on mitochondrial-respiration: overshooting statistically significant several-fold increase of most oxygen-consumption-rate (OCR) parameters vs. significantly decreased all OCR parameters, respectively. Chronic low doses of 3-nitropropionic acid (3-NP) (CoII inhibitor) did not induce long-lasting changes in the cells\u2019 mitochondria-related parameters. Intraperitoneal administration of 0.75\u2009mg\/kg\/day rotenone to male mice for 4 or 8 weeks did not affect spontaneous and motor activity, caused behaviors associated with mania and depression following 4 and 8 weeks, respectively, accompanied by relevant changes in mitochondrial basal OCR and in levels of mitochondrial-respiration proteins. Our model is among the very few BD-like animal models exhibiting construct (mild mitochondrial dysfunction), face (decreased\/increased immobility time in the forced-swim test, increased\/decreased consumption of sweet solution, increased\/decreased time spent in the open arms of the elevated plus maze) and predictive (reversal of rotenone-induced behavioral changes by lithium treatment) validity. Our rotenone regime, employing doses that, to the best of our knowledge, have never been used before, differs from those inducing Parkinson\u2019s-like models by not affecting ROS-levels and cell-viability in vitro nor motor activity in vivo.<\/jats:p>","DOI":"10.1038\/s41398-021-01215-y","type":"journal-article","created":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T22:00:19Z","timestamp":1613167219000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Using mitochondrial respiration inhibitors to design a novel model of bipolar disorder-like phenotype with construct, face and predictive validity"],"prefix":"10.1038","volume":"11","author":[{"given":"O.","family":"Damri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Asslih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Shemesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Natour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4825-6278","authenticated-orcid":false,"given":"O.","family":"Noori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Daraushe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7025-5541","authenticated-orcid":false,"given":"H.","family":"Einat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Kara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Las","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Agam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,12]]},"reference":[{"key":"1215_CR1","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1002\/ddrr.115","volume":"16","author":"F Scaglia","year":"2010","unstructured":"Scaglia, F. The role of mitochondrial dysfunction in psychiatric disease. Dev. Disabil. Res. Rev. 16, 136\u2013143 (2010).","journal-title":"Dev. Disabil. Res. Rev."},{"key":"1215_CR2","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/cns.12655","volume":"23","author":"M Golpich","year":"2017","unstructured":"Golpich, M. et al. Mitochondrial dysfunction and biogenesis in neurodegenerative diseases: pathogenesis and treatment. CNS Neurosci. Therapeutics 23, 5\u201322 (2017).","journal-title":"CNS Neurosci. Therapeutics"},{"key":"1215_CR3","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/nrn3229","volume":"13","author":"H Manji","year":"2012","unstructured":"Manji, H. et al. Impaired mitochondrial function in psychiatric disorders. Nat. Rev. Neurosci. 13, 293\u2013307 (2012).","journal-title":"Nat. Rev. Neurosci."},{"key":"1215_CR4","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.molmed.2019.07.002","volume":"26","author":"G Lou","year":"2020","unstructured":"Lou, G. et al. Mitophagy and neuroprotection. Trends Mol. Med. 26, 8\u201320 (2020).","journal-title":"Trends Mol. Med."},{"key":"1215_CR5","doi-asserted-by":"publisher","first-page":"575","DOI":"10.2353\/ajpath.2010.081068","volume":"177","author":"AM Cataldo","year":"2010","unstructured":"Cataldo, A. M. et al. Abnormalities in mitochondrial structure in cells from patients with bipolar disorder. Am. J. Pathol. 177, 575\u2013585 (2010).","journal-title":"Am. J. Pathol."},{"key":"1215_CR6","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1038\/sj.mp.4001711","volume":"10","author":"C Stork","year":"2005","unstructured":"Stork, C. & Renshaw, P. F. Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research. Mol. Psychiatry 10, 900\u2013919 (2005).","journal-title":"Mol. Psychiatry"},{"key":"1215_CR7","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1001\/archpsyc.61.5.450","volume":"61","author":"SR Dager","year":"2004","unstructured":"Dager, S. R. et al. Brain metabolic alterations in medication-free patients with bipolar disorder. Arch. Gen. Psychiatry 61, 450\u2013458 (2004).","journal-title":"Arch. Gen. Psychiatry"},{"key":"1215_CR8","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1034\/j.1399-5618.2000.020305.x","volume":"2","author":"T Kato","year":"2000","unstructured":"Kato, T. & Kato, N. Mitochondrial dysfunction in bipolar disorder. Bipolar Disord. 2, 180\u2013190 (2000).","journal-title":"Bipolar Disord."},{"key":"1215_CR9","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1111\/j.1399-5618.2009.00729.x","volume":"11","author":"IC Maurer","year":"2009","unstructured":"Maurer, I. C., Schippel, P. & Volz, H. P. Lithium-induced enhancement of mitochondrial oxidative phosphorylation in human brain tissue. Bipolar Disord. 11, 515\u2013522 (2009).","journal-title":"Bipolar Disord."},{"key":"1215_CR10","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1093\/ijnp\/pyy018","volume":"21","author":"C Pereira","year":"2018","unstructured":"Pereira, C. et al. Mitochondrial agents for bipolar disorder. Int. J. Neuropsychopharmacol. 21, 550\u2013569 (2018).","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"1215_CR11","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1111\/j.1601-5215.2011.00548.x","volume":"23","author":"G Scaini","year":"2011","unstructured":"Scaini, G. et al. Activity of mitochondrial respiratory chain is increased by chronic administration of antidepressants. Acta Neuropsychiatrica 23, 112\u2013118 (2011).","journal-title":"Acta Neuropsychiatrica"},{"key":"1215_CR12","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.neulet.2010.10.037","volume":"487","author":"FR Agostinho","year":"2011","unstructured":"Agostinho, F. R. et al. Treatment with olanzapine, fluoxetine and olanzapine\/fluoxetine alters citrate synthase activity in rat brain. Neurosci. Lett. 487, 278\u2013281 (2011).","journal-title":"Neurosci. Lett."},{"key":"1215_CR13","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/npp.2013.194","volume":"39","author":"L Toker","year":"2014","unstructured":"Toker, L. et al. Inositol-related gene knockouts mimic lithium\u2019s effect on mitochondrial function. Neuropsychopharmacology 39, 319\u2013328 (2014).","journal-title":"Neuropsychopharmacology"},{"key":"1215_CR14","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1038\/81834","volume":"3","author":"R Betarbet","year":"2000","unstructured":"Betarbet, R. et al. Chronic systemic pesticide exposure reproduces features of Parkinson\u2019s disease. Nat. Neurosci. 3, 1301\u20131306 (2000).","journal-title":"Nat. Neurosci."},{"key":"1215_CR15","doi-asserted-by":"publisher","first-page":"461","DOI":"10.3233\/JPD-130230","volume":"3","author":"V Dias","year":"2013","unstructured":"Dias, V., Junn, E. & Mouradian, M. M. The role of oxidative stress in Parkinson\u2019s disease. J. Parkinson\u2019s Dis. 3, 461\u2013491 (2013).","journal-title":"J. Parkinson\u2019s Dis."},{"key":"1215_CR16","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.biopha.2015.11.009","volume":"77","author":"SB Dhadde","year":"2016","unstructured":"Dhadde, S. B. et al. Effect of embelin against 3-nitropropionic acid-induced Huntington\u2019s disease in rats. Biomed. Pharmacother. 77, 52\u201358 (2016).","journal-title":"Biomed. Pharmacother."},{"key":"1215_CR17","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1111\/j.1471-4159.2007.04996.x","volume":"104","author":"M Pandey","year":"2008","unstructured":"Pandey, M. et al. Mitochondrial NAD+-linked state 3 respiration and complex-I activity are compromised in the cerebral cortex of 3-nitropropionic acid-induced rat model of Huntington\u2019s disease. J. Neurochem. 104, 420\u2013434 (2008).","journal-title":"J. Neurochem."},{"key":"1215_CR18","doi-asserted-by":"crossref","unstructured":"Brouillet, E. The 3-NP model of striatal neurodegeneration. Curr. Protoc. Neurosci. 67, 9.48.1\u20139.48.14 (2014).","DOI":"10.1002\/0471142301.ns0948s67"},{"key":"1215_CR19","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.neuro.2014.12.002","volume":"46","author":"ME Johnson","year":"2015","unstructured":"Johnson, M. E. & Bobrovskaya, L. An update on the rotenone models of Parkinson\u2019s disease: their ability to reproduce the features of clinical disease and model gene-environment interactions. Neurotoxicology 46, 101\u2013116 (2015).","journal-title":"Neurotoxicology"},{"key":"1215_CR20","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1007\/s12035-014-9086-x","volume":"53","author":"D Colle","year":"2016","unstructured":"Colle, D. et al. Succinobucol, a lipid-lowering drug, protects against 3-nitropropionic acid-induced mitochondrial dysfunction and oxidative stress in SH-SY5Y Cells via upregulation of glutathione levels and glutamate cysteine ligase Activity. Mol. Neurobiol. 53, 1280\u20131295 (2016).","journal-title":"Mol. Neurobiol."},{"key":"1215_CR21","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.brainres.2010.03.102","volume":"1337","author":"FM Lopes","year":"2010","unstructured":"Lopes, F. M. et al. Comparison between proliferative and neuron-like SH-SY5Y cells as an in vitro model for Parkinson disease studies. Brain Res. 1337, 85\u201394 (2010).","journal-title":"Brain Res."},{"key":"1215_CR22","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1159\/000492717","volume":"102","author":"G Shemesh","year":"2018","unstructured":"Shemesh, G., Kara, N., Carmi & Einat, H. Chronic stress may not be a Factor in the behavioral response to chronic lithium in ICR mice. Pharmacology 102, 281\u2013286 (2018).","journal-title":"Pharmacology"},{"key":"1215_CR23","doi-asserted-by":"publisher","first-page":"11960","DOI":"10.1073\/pnas.0904875106","volume":"106","author":"K Mitra","year":"2009","unstructured":"Mitra, K., Wunder, C., Roysam, B., Lin, G. & Lippincott-Schwartz, J. A hyperfused mitochondrial state achieved at G1-S regulates cyclin E buildup and entry into S phase. Proc. Natl Acad. Sci. USA 106, 11960\u201311965 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1215_CR24","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/B978-0-12-801415-8.00013-8","volume":"547","author":"BM Polster","year":"2014","unstructured":"Polster, B. M., Nicholls, D. G., Ge, S. X. & Roelofs, B. A. Use of potentiometric fluorophores in the measurement of mitochondrial reactive oxygen species. Methods Enzymol. 547, 225\u2013250 (2014).","journal-title":"Methods Enzymol."},{"key":"1215_CR25","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1111\/j.1399-5618.2004.00162.x","volume":"7","author":"A Shamir","year":"2005","unstructured":"Shamir, A., Elhadad, N., Belmaker, R. H. & Agam, G. Interaction of calbindin D28k and inositol monophosphatase in human postmortem cortex: possible implications for bipolar disorder. Bipolar Disord. 7, 42\u201348 (2005).","journal-title":"Bipolar Disord."},{"key":"1215_CR26","doi-asserted-by":"publisher","first-page":"rs2","DOI":"10.1126\/scisignal.2005966","volume":"8","author":"KA Janes","year":"2015","unstructured":"Janes, K. A. An analysis of critical factors for quantitative immunoblotting. Sci. Signal. 8, rs2 (2015).","journal-title":"Sci. Signal."},{"key":"1215_CR27","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1177\/0269881108097905","volume":"24","author":"S Flaisher-Grinberg","year":"2010","unstructured":"Flaisher-Grinberg, S., Kronfeld-Schor, N. & Einat, H. Models of mania: from facets to domains and from animal models to model animals. J. Psychopharmacol. 24, 437\u2013438 (2010).","journal-title":"J. Psychopharmacol."},{"key":"1215_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-36040-9","volume":"8","author":"S Jang","year":"2018","unstructured":"Jang, S. & Javadov, S. Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria. Sci. Rep. 8, 17732 (2018).","journal-title":"Sci. Rep."},{"key":"1215_CR29","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.ymeth.2008.09.026","volume":"46","author":"DM Medeiros","year":"2008","unstructured":"Medeiros, D. M. Assessing mitochondria biogenesis. Methods 46, 288\u2013294 (2008).","journal-title":"Methods"},{"key":"1215_CR30","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1177\/070674370705201202","volume":"52","author":"JF Wang","year":"2007","unstructured":"Wang, J. F. Defects of mitochondrial electron transport chain in bipolar disorder: implications for mood-stabilizing treatment. Can. J. Psychiatry 52, 753\u2013762 (2007).","journal-title":"Can. J. Psychiatry"},{"key":"1215_CR31","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1007\/7854_2010_108","volume":"7","author":"V Krishnan","year":"2011","unstructured":"Krishnan, V. & Nestler, E. J. Animal models of depression: molecular perspectives. Curr. Top. Behav. Neurosci. 7, 121\u2013147 (2011).","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"1215_CR32","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.neuroscience.2015.08.041","volume":"321","author":"RW Logan","year":"2016","unstructured":"Logan, R. W. & McClung, C. A. Animal models of bipolar mania: The past, present and future. Neuroscience 321, 163\u2013188 (2016).","journal-title":"Neuroscience"},{"key":"1215_CR33","first-page":"35","volume":"54","author":"M Deutsch-Feldman","year":"2015","unstructured":"Deutsch-Feldman, M., Picetti, R., Seip-Cammack, K., Zhou, Y. & Kreek, M. J. Effects of handling and vehicle injections on adrenocorticotropic and corticosterone concentrations in Sprague-Dawley compared with Lewis rats. J. Am. Assoc. Lab Anim. Sci. 54, 35\u201339 (2015).","journal-title":"J. Am. Assoc. Lab Anim. Sci."},{"key":"1215_CR34","first-page":"12","volume":"4","author":"ID Neumann","year":"2010","unstructured":"Neumann, I. D., Veenema, A. H. & Beiderbeck, D. I. Aggression and anxiety: social context and neurobiological links. Front. Behav. Neurosci. 4, 12 (2010).","journal-title":"Front. Behav. Neurosci."},{"key":"1215_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neubiorev.2017.01.014","volume":"74","author":"G Morris","year":"2017","unstructured":"Morris, G. et al. A model of the mitochondrial basis of bipolar disorder. Neurosci. Biobehav. Rev. 74, 1\u201320 (2017).","journal-title":"Neurosci. Biobehav. Rev."},{"key":"1215_CR36","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1001\/archpsyc.61.3.300","volume":"61","author":"C Konradi","year":"2004","unstructured":"Konradi, C. et al. Molecular evidence for mitochondrial dysfunction in bipolar disorder. Arch. Gen. Psychiatry 61, 300\u2013308 (2004).","journal-title":"Arch. Gen. Psychiatry"},{"key":"1215_CR37","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1001\/archgenpsychiatry.2010.22","volume":"67","author":"AC Andreazza","year":"2010","unstructured":"Andreazza, A. C., Shao, L., Wang, J. F. & Young, L. T. Mitochondrial complex I activity and oxidative damage to mitochondrial proteins in the prefrontal cortex of patients with bipolar disorder. Arch. Gen. Psychiatry 67, 360\u2013368 (2010).","journal-title":"Arch. Gen. Psychiatry"},{"key":"1215_CR38","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1016\/j.euroneuro.2010.12.001","volume":"21","author":"MJ Kas","year":"2011","unstructured":"Kas, M. J. et al. Advances in multidisciplinary and cross-species approaches to examine the neurobiology of psychiatric disorders. Eur. Neuropsychopharmacol. 21, 532\u2013544 (2011).","journal-title":"Eur. Neuropsychopharmacol."},{"key":"1215_CR39","first-page":"3680","volume":"16","author":"Y Yang","year":"2018","unstructured":"Yang, Y. et al. MFN2 ameliorates cell apoptosis in a cellular model of Parkinson\u2019s disease induced by rotenone. Exp. Ther. Med. 16, 3680\u20133685 (2018).","journal-title":"Exp. Ther. Med."},{"key":"1215_CR40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0044610","volume":"7","author":"S Giordano","year":"2012","unstructured":"Giordano, S., Lee, J., Darley-Usmar, V. M. & Zhang, J. Distinct effects of rotenone, 1-methyl-4-phenylpyridinium and 6-hydroxydopamine on cellular bioenergetics and cell death. PLoS ONE 7, e44610 (2012).","journal-title":"PLoS ONE"},{"key":"1215_CR41","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1093\/toxsci\/kfh089","volume":"79","author":"K Newhouse","year":"2004","unstructured":"Newhouse, K. et al. Rotenone-induced apoptosis is mediated by p38 and JNK MAP kinases in human dopaminergic SH-SY5Y cells. Toxicol. Sci. 79, 137\u2013146 (2004).","journal-title":"Toxicol. Sci."},{"key":"1215_CR42","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1124\/jpet.107.127597","volume":"323","author":"M Watabe","year":"2007","unstructured":"Watabe, M. & Nakaki, T. Mitochondrial complex I inhibitor rotenone-elicited dopamine redistribution from vesicles to cytosol in human dopaminergic SH-SY5Y cells. J. Pharmacol. Exp. Therapeutics 323, 499\u2013507 (2007).","journal-title":"J. Pharmacol. Exp. Therapeutics"},{"key":"1215_CR43","doi-asserted-by":"publisher","first-page":"270","DOI":"10.2203\/dose-response.12-005.Gao","volume":"11","author":"X Yuyun","year":"2013","unstructured":"Yuyun, X. et al. Effects of low concentrations of rotenone upon mitohormesis in SH-SY5Y Cells. Dose Response 11, 270\u2013280 (2013).","journal-title":"Dose Response"},{"key":"1215_CR44","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1111\/j.1432-1033.1994.tb19985.x","volume":"219","author":"T Friedrich","year":"1994","unstructured":"Friedrich, T. et al. Two binding sites of inhibitors in NADH: ubiquinone oxidoreductase (complex I). Relationship of one site with the ubiquinone-binding site of bacterial glucose:ubiquinone oxidoreductase. Eur. J. Biochem. 219, 691\u2013698 (1994).","journal-title":"Eur. J. Biochem."},{"key":"1215_CR45","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/j.cmet.2014.01.011","volume":"19","author":"J Yun","year":"2014","unstructured":"Yun, J. & Finkel, T. Mitohormesis. Cell Metab. 19, 757\u2013766 (2014).","journal-title":"Cell Metab."},{"key":"1215_CR46","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.cmet.2007.08.011","volume":"6","author":"TJ Schulz","year":"2007","unstructured":"Schulz, T. J. et al. Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell Metab. 6, 280\u2013293 (2007).","journal-title":"Cell Metab."},{"key":"1215_CR47","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1083\/jcb.201008084","volume":"191","author":"SM Jin","year":"2010","unstructured":"Jin, S. M. et al. Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL. J. Cell Biol. 191, 933\u2013942 (2010).","journal-title":"J. Cell Biol."},{"key":"1215_CR48","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/nature12188","volume":"497","author":"RH Houtkooper","year":"2013","unstructured":"Houtkooper, R. H. et al. Mitonuclear protein imbalance as a conserved longevity mechanism. Nature 497, 451\u2013457 (2013).","journal-title":"Nature"},{"key":"1215_CR49","doi-asserted-by":"publisher","first-page":"657","DOI":"10.3389\/fnins.2017.00657","volume":"11","author":"L Yu","year":"2017","unstructured":"Yu, L. et al. Neurochemical and behavior deficits in rats with iron and rotenone co-treatment: role of redox imbalance and neuroprotection by biochanin A. Front. Neurosci. 11, 657 (2017).","journal-title":"Front. Neurosci."},{"key":"1215_CR50","doi-asserted-by":"publisher","first-page":"175","DOI":"10.3389\/fnbeh.2013.00175","volume":"7","author":"FL Campos","year":"2013","unstructured":"Campos, F. L. et al. Rodent models of Parkinson\u2019s disease: beyond the motor symptomatology. Front. Behav. Neurosci. 7, 175 (2013).","journal-title":"Front. Behav. Neurosci."},{"key":"1215_CR51","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.brainres.2018.10.002","volume":"1704","author":"V Walia","year":"2019","unstructured":"Walia, V., Garg, C. & Garg, M. NO-sGC-cGMP signaling influence the anxiolytic like effect of lithium in mice in light and dark box and elevated plus maze. Brain Res. 1704, 114\u2013126 (2019).","journal-title":"Brain Res."},{"key":"1215_CR52","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1016\/j.jad.2013.06.043","volume":"151","author":"E Zeschel","year":"2013","unstructured":"Zeschel, E. et al. The bipolar disorder prodrome revisited: Is there a symptomatic pattern? J. Affect Disord. 151, 551\u2013560 (2013).","journal-title":"J. Affect Disord."},{"key":"1215_CR53","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-019-0494-6","volume":"9","author":"SS Valvassori","year":"2019","unstructured":"Valvassori, S. S. et al. Validation of the animal model of bipolar disorder induced by Ouabain: face, construct and predictive perspectives. Transl. Psychiatry 9, 158 (2019).","journal-title":"Transl. Psychiatry"},{"key":"1215_CR54","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s12868-019-0508-6","volume":"20","author":"C Liu","year":"2019","unstructured":"Liu, C., Pu, W. D., Wu, G. W., Zhao, J. & Xue, Z. M. Abnormal resting-state cerebral-limbic functional connectivity in bipolar depression and unipolar depression. Bmc Neurosci. 20, 30\u201338 (2019).","journal-title":"Bmc Neurosci."},{"key":"1215_CR55","doi-asserted-by":"publisher","first-page":"3440","DOI":"10.1093\/brain\/awv266","volume":"138","author":"C Abe","year":"2015","unstructured":"Abe, C. et al. Manic episodes are related to changes in frontal cortex: a longitudinal neuroimaging study of bipolar disorder 1. Brain 138, 3440\u20133448 (2015).","journal-title":"Brain"},{"key":"1215_CR56","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1038\/mp.2015.69","volume":"21","author":"L Schmaal","year":"2016","unstructured":"Schmaal, L. et al. Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group. Mol. Psychiatry 21, 806\u2013812 (2016).","journal-title":"Mol. Psychiatry"},{"key":"1215_CR57","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.biopsycho.2012.01.008","volume":"90","author":"LG Chepenik","year":"2012","unstructured":"Chepenik, L. G. et al. Structure-function associations in hippocampus in bipolar disorder. Biol. Psychol. 90, 18\u201322 (2012).","journal-title":"Biol. Psychol."},{"key":"1215_CR58","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.1038\/mp.2016.262","volume":"22","author":"B Cao","year":"2017","unstructured":"Cao, B. et al. Hippocampal subfield volumes in mood disorders. Mol. Psychiatry 22, 1352\u20131358 (2017).","journal-title":"Mol. Psychiatry"},{"key":"1215_CR59","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.pbb.2011.01.017","volume":"98","author":"M Moretti","year":"2011","unstructured":"Moretti, M. et al. Tamoxifen effects on respiratory chain complexes and creatine kinase activities in an animal model of mania. Pharm. Biochem. Behav. 98, 304\u2013310 (2011).","journal-title":"Pharm. Biochem. Behav."},{"key":"1215_CR60","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/j.pbb.2012.09.010","volume":"103","author":"G Feier","year":"2013","unstructured":"Feier, G. et al. Lithium and valproate modulate energy metabolism in an animal model of mania induced by methamphetamine. Pharm. Biochem. Behav. 103, 589\u2013596 (2013).","journal-title":"Pharm. Biochem. Behav."},{"key":"1215_CR61","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1111\/j.1399-5618.2010.00882.x","volume":"12","author":"RD Beech","year":"2010","unstructured":"Beech, R. D. et al. Increased peripheral blood expression of electron transport chain genes in bipolar depression. Bipolar Disord. 12, 813\u2013824 (2010).","journal-title":"Bipolar Disord."},{"key":"1215_CR62","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1002\/jnr.23810","volume":"95","author":"CA Orsini","year":"2017","unstructured":"Orsini, C. A. & Setlow, B. Sex differences in animal models of decision making. J. Neurosci. Res. 95, 260\u2013269 (2017).","journal-title":"J. Neurosci. Res."},{"key":"1215_CR63","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1016\/S0140-6736(20)31561-0","volume":"396","author":"F Mauvais-Jarvis","year":"2020","unstructured":"Mauvais-Jarvis, F., Merz, N. B. & Barnes, P. J. Sex and gender: modifiers of health, disease, and medicine (vol 396, pg 565, 2020). Lancet 396, 668\u2013668 (2020).","journal-title":"Lancet"}],"container-title":["Translational Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41398-021-01215-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-021-01215-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-021-01215-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,21]],"date-time":"2023-10-21T03:53:53Z","timestamp":1697860433000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41398-021-01215-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,12]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["1215"],"URL":"https:\/\/doi.org\/10.1038\/s41398-021-01215-y","relation":{},"ISSN":["2158-3188"],"issn-type":[{"value":"2158-3188","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,12]]},"assertion":[{"value":"1 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 December 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 December 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"123"}}