Illuminating the Function of the Hydroxyl Radical in the Brains of Mice with Depression Phenotypes by Two-Photon Fluorescence Imaging.

Depression is intimately linked with oxidative stress. As one of the most reactive and oxidative reactive oxygen species that is overproduced during oxidative stress, the hydroxyl radical (. OH) can cause macromolecular damage and subsequent neurological diseases. However, due to the high reactivity and low concentration of . OH, precise exploration of . OH in brains remains a challenge. The two-photon fluorescence probe MD-B was developed for in situ . OH imaging in living systems. This probe achieves exceptional selectivity towards . OH through the one-electron oxidation of 3-methyl-pyrazolone as a new specific recognition site. MD-B can be used to map . OH in mouse brain, thereby revealing that increased . OH is positively correlated with the severity of depression phenotypes. Furthermore, . OH has been shown to inactivate deacetylase SIRT1, thereby leading to the occurrence and development of depression phenotypes. This work provides a new strategy for the future treatment of depression.

[1]  J. Sessler,et al.  An ESIPT Probe for the Ratiometric Imaging of Peroxynitrite Facilitated by Binding to Aβ-Aggregates. , 2018, Journal of the American Chemical Society.

[2]  H. Tian,et al.  Photocontrolled Fluorescence "Double-Check" Bioimaging Enabled by a Glycoprobe-Protein Hybrid. , 2018, Journal of the American Chemical Society.

[3]  Juyoung Yoon,et al.  Recent progress in the development of fluorescent, luminescent and colorimetric probes for detection of reactive oxygen and nitrogen species. , 2016, Chemical Society reviews.

[4]  Zhongpin Zhang,et al.  Real-Time Discrimination and Versatile Profiling of Spontaneous Reactive Oxygen Species in Living Organisms with a Single Fluorescent Probe. , 2016, Journal of the American Chemical Society.

[5]  Zhihong Liu,et al.  A Rationally Designed Upconversion Nanoprobe for in Vivo Detection of Hydroxyl Radical. , 2015, Journal of the American Chemical Society.

[6]  Warren W. Kretzschmar,et al.  Sparse whole genome sequencing identifies two loci for major depressive disorder , 2015, Nature.

[7]  Hwan Myung Kim,et al.  Small-molecule two-photon probes for bioimaging applications. , 2015, Chemical reviews.

[8]  Li Zhang,et al.  DNA-templated Ag nanoclusters as fluorescent probes for sensing and intracellular imaging of hydroxyl radicals. , 2014, Talanta.

[9]  Changqin Ding,et al.  Ratiometric fluorescence probe for monitoring hydroxyl radical in live cells based on gold nanoclusters. , 2014, Analytical chemistry.

[10]  Sung-Kyun Ko,et al.  Rhodamine cyclic hydrazide as a fluorescent probe for the detection of hydroxyl radicals. , 2013, Chemical communications.

[11]  M. Weyand,et al.  Ex-527 inhibits Sirtuins by exploiting their unique NAD+-dependent deacetylation mechanism , 2013, Proceedings of the National Academy of Sciences.

[12]  Srinivasa R. Mandalapu,et al.  New rhodamine nitroxide based fluorescent probes for intracellular hydroxyl radical identification in living cells. , 2012, Organic letters.

[13]  M. Berk,et al.  A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness , 2011, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[14]  I. Warner,et al.  Ratiometric coumarin-neutral red (CONER) nanoprobe for detection of hydroxyl radicals. , 2011, Analytical chemistry.

[15]  Lin Yuan,et al.  Ratiometric fluorescent detection of intracellular hydroxyl radicals based on a hybrid coumarin-cyanine platform. , 2010, Chemical communications.

[16]  B. Tang,et al.  A new highly selective and sensitive assay for fluorescence imaging of *OH in living cells: effectively avoiding the interference of peroxynitrite. , 2010, Chemistry.

[17]  David J. Begley,et al.  Structure and function of the blood–brain barrier , 2010, Neurobiology of Disease.

[18]  M. Araie,et al.  Edaravone, a Free Radical Scavenger, Protects against Retinal Damage in Vitro and in Vivo , 2009, Journal of Pharmacology and Experimental Therapeutics.

[19]  B. Cho,et al.  Two-photon probes for intracellular free metal ions, acidic vesicles, and lipid rafts in live tissues. , 2009, Accounts of chemical research.

[20]  Eric J. Nestler,et al.  The molecular neurobiology of depression , 2008, Nature.

[21]  A. Borst,et al.  A genetically encoded calcium indicator for chronic in vivo two-photon imaging , 2008, Nature Methods.

[22]  Guozhong Xu,et al.  Hydroxyl radical-mediated modification of proteins as probes for structural proteomics. , 2007, Chemical reviews.

[23]  P. Puigserver,et al.  Resveratrol Improves Mitochondrial Function and Protects against Metabolic Disease by Activating SIRT1 and PGC-1α , 2006, Cell.

[24]  Takayoshi Suzuki,et al.  Hydroxyl radical scavenging by edaravone derivatives: Efficient scavenging by 3-methyl-1-(pyridin-2-yl)-5-pyrazolone with an intramolecular base. , 2006, Bioorganic & medicinal chemistry letters.

[25]  A. Frazer,et al.  Leptin: A potential novel antidepressant , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[26]  W. Denk,et al.  Deep tissue two-photon microscopy , 2005, Nature Methods.

[27]  S. Khanzode,et al.  Oxidative damage and major depression: the potential antioxidant action of selective serotonin re-uptake inhibitors , 2003, Redox report : communications in free radical research.

[28]  R. Waterhouse,et al.  Determination of lipophilicity and its use as a predictor of blood-brain barrier penetration of molecular imaging agents. , 2003, Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging.

[29]  C. Stosiek,et al.  In vivo two-photon calcium imaging of neuronal networks , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[30]  M. Barrot,et al.  Neurobiology of Depression , 2002, Neuron.

[31]  M. Bekaroǧlu,et al.  Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments. , 2001, Journal of affective disorders.

[32]  F. Hsu,et al.  Mass Spectrometric Quantification of Markers for Protein Oxidation by Tyrosyl Radical, Copper, and Hydroxyl Radical in Low Density Lipoprotein Isolated from Human Atherosclerotic Plaques* , 1997, The Journal of Biological Chemistry.

[33]  M. Beal.  Mitochondria, free radicals, and neurodegeneration , 1996, Current Opinion in Neurobiology.

[34]  N. Polissar,et al.  Progression of human breast cancers to the metastatic state is linked to hydroxyl radical-induced DNA damage. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[35]  B. Freeman,et al.  Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[36]  M Danhof,et al.  Characterization of an "in vitro" blood-brain barrier: effects of molecular size and lipophilicity on cerebrovascular endothelial transport rates of drugs. , 1988, The Journal of pharmacology and experimental therapeutics.

[37]  D. Choi,et al.  Glutamate neurotoxicity and diseases of the nervous system , 1988, Neuron.

[38]  D. Gerlier,et al.  Use of MTT colorimetric assay to measure cell activation. , 1986, Journal of immunological methods.

[39]  L. Nowak,et al.  Magnesium gates glutamate-activated channels in mouse central neurones , 1984, Nature.

[40]  George A. Reynolds,et al.  New coumarin dyes with rigidized structure for flashlamp-pumped dye lasers , 1975 .

[41]  S. Goldstein,et al.  Mannitol as an OH. scavenger in aqueous solutions and in biological systems. , 1984, International journal of radiation biology and related studies in physics, chemistry, and medicine.