{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T23:23:08Z","timestamp":1768778588893,"version":"3.49.0"},"reference-count":65,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T00:00:00Z","timestamp":1583193600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009347","name":"Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz","doi-asserted-by":"publisher","award":["2000"],"award-info":[{"award-number":["2000"]}],"id":[{"id":"10.13039\/501100009347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Adult neurogenesis occurs in the dentate gyrus (DG) of the hippocampus. New neurons help to counteract the effects of stress and several interventions including antidepressant drugs, environmental modifications and internal factors act pro-neurogenic with consequences in the dorsal and ventral DG. Melatonin, the main product synthesized by the pineal gland, induces antidepressant-like effects and modulates several events of the neurogenic process. However, the information related to the capability of melatonin to modulate dendrite maturation and complexity in the dorsal and ventral regions of the DG and their correlation with its antidepressant-like effect is absent. Thus, in this study, we analyzed the impact of melatonin (0, 0.5, 1, 2.5, 5 or 10 mg\/kg) administered daily for fourteen days on the number, dendrite complexity and distribution of doublecortin (DCX)-cells in the dorsal-ventral regions of the DG in male Balb\/C mice. Doublecortin is a microtubule-associated protein that is expressed during the course of dendritic maturation of newborn neurons. Also, we analyzed the impact of melatonin on despair-like behavior in the forced swim test. We first found a significant increase in the number and higher dendrite complexity, mainly with the doses of 2.5, 5 and 10 mg\/kg of melatonin (81%, 122%, 78%). These cells showed more complex dendritic trees in the ventral- and the dorsal- DG. Concomitantly, the doses of 5 and 10 mg\/kg of melatonin decreased depressant-like behavior (76%, 82%). Finally, the data corroborate the antidepressant-like effect of melatonin and the increasing number of doublecortin-associated cells. Besides, the data indicate that melatonin favors the number and dendrite complexity of DCX-cells in the dorsal- and ventral- region of the DG, which may explain part of the antidepressant-like effect of melatonin.<\/jats:p>","DOI":"10.3390\/ijms21051724","type":"journal-article","created":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T13:06:23Z","timestamp":1583240783000},"page":"1724","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Melatonin Modulates Dendrite Maturation and Complexity in the Dorsal- and Ventral- Dentate Gyrus Concomitantly with Its Antidepressant-Like Effect in Male Balb\/C Mice"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3243-1588","authenticated-orcid":false,"given":"Gerardo Bernab\u00e9","family":"Ram\u00edrez-Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Laboratory of Neurogenesis, Division of Clinical Investigations, National Institute of Psychiatry \u201cRam\u00f3n de la Fuente Mu\u00f1iz\u201d, Calzada Mexico-Xochimilco No. 101, Mexico City C.P. 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana Montserrat","family":"Palacios-Cabriales","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenesis, Division of Clinical Investigations, National Institute of Psychiatry \u201cRam\u00f3n de la Fuente Mu\u00f1iz\u201d, Calzada Mexico-Xochimilco No. 101, Mexico City C.P. 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo","family":"Ortiz-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenesis, Division of Clinical Investigations, National Institute of Psychiatry \u201cRam\u00f3n de la Fuente Mu\u00f1iz\u201d, Calzada Mexico-Xochimilco No. 101, Mexico City C.P. 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6634-7494","authenticated-orcid":false,"given":"Erika Montserrat","family":"Estrada-Camarena","sequence":"additional","affiliation":[{"name":"Laboratory of Neuropsychopharmacology, Division of Neurosciences, National Institute of Psychiatry \u201cRam\u00f3n de la Fuente Mu\u00f1iz\u201d, Calzada Mexico-Xochimilco No. 101, Mexico City C.P. 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelly Maritza","family":"Vega-Rivera","sequence":"additional","affiliation":[{"name":"Laboratory of Neuropsychopharmacology, Division of Neurosciences, National Institute of Psychiatry \u201cRam\u00f3n de la Fuente Mu\u00f1iz\u201d, Calzada Mexico-Xochimilco No. 101, Mexico City C.P. 14370, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1111\/j.1460-9568.2011.07599.x","article-title":"Seven principles in the regulation of adult neurogenesis","volume":"33","author":"Kempermann","year":"2011","journal-title":"Eur. J. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1002\/9780470751251.ch12","article-title":"Hippocampal neurogenesis and depression","volume":"289","author":"Sahay","year":"2008","journal-title":"Novartis Found. Symp."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/nature10287","article-title":"Adult hippocampal neurogenesis buffers stress responses and depressive behaviour","volume":"476","author":"Snyder","year":"2011","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/npp.2009.130","article-title":"Antidepressants, age, and neuroprogenitors","volume":"35","author":"Boldrini","year":"2010","journal-title":"Neuropsychopharmacology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2376","DOI":"10.1038\/npp.2009.75","article-title":"Antidepressants increase neural progenitor cells in the human hippocampus","volume":"34","author":"Boldrini","year":"2009","journal-title":"Neuropsychopharmacology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1176\/appi.ajp.161.4.598","article-title":"Lower hippocampal volume in patients suffering from depression: A meta-analysis","volume":"161","author":"Campbell","year":"2004","journal-title":"Am. J. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1073\/pnas.0337481100","article-title":"Course of illness, hippocampal function, and hippocampal volume in major depression","volume":"100","author":"MacQueen","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","first-page":"196","article-title":"Implications of adult hippocampal neurogenesis in antidepressant action","volume":"29","author":"Malberg","year":"2004","journal-title":"J. Psychiatry Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1177\/1073858408317242","article-title":"Cognitive role of neurogenesis in depression and antidepressant treatment","volume":"14","author":"Perera","year":"2008","journal-title":"Neuroscientist"},{"key":"ref_10","first-page":"94","article-title":"Increase in neurogenesis and behavioural benefit after chronic fluoxetine treatment in Wistar rats","volume":"117","author":"Marcussen","year":"2008","journal-title":"Acta Neurol. Scand."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1523\/JNEUROSCI.3632-07.2008","article-title":"Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells","volume":"28","author":"Wang","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1038\/nn1969","article-title":"Adult hippocampal neurogenesis in depression","volume":"10","author":"Sahay","year":"2007","journal-title":"Nat. Neurosci."},{"key":"ref_13","first-page":"84","article-title":"Antidepressant effects of exercise: Evidence for an adult-neurogenesis hypothesis?","volume":"31","author":"Ernst","year":"2006","journal-title":"J. Psychiatry Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.bbr.2015.12.028","article-title":"The neurogenic effects of an enriched environment and its protection against the behavioral consequences of chronic mild stress persistent after enrichment cessation in six-month-old female Balb\/C mice","volume":"301","year":"2016","journal-title":"Behav. Brain Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1038\/npp.2009.46","article-title":"Melatonin modulates cell survival of new neurons in the hippocampus of adult mice","volume":"34","author":"Klempin","year":"2009","journal-title":"Neuropsychopharmacology"},{"key":"ref_16","first-page":"123","article-title":"Melatonin treatment mimics the antidepressant action in chronic corticosterone-treated mice","volume":"49","author":"Crupi","year":"2010","journal-title":"J. Pineal Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1111\/j.1600-079X.2011.00897.x","article-title":"Melatonin\u2019s stimulatory effect on adult hippocampal neurogenesis in mice persists after ovariectomy","volume":"51","author":"Crupi","year":"2011","journal-title":"J. Pineal Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s00213-011-2280-x","article-title":"Chronic agomelatine treatment corrects behavioral, cellular, and biochemical abnormalities induced by prenatal stress in rats","volume":"217","author":"Mairesse","year":"2011","journal-title":"Psychopharmacology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.physbeh.2013.06.015","article-title":"Melatonin ameliorates chronic mild stress induced behavioral dysfunctions in mice","volume":"119","author":"Haridas","year":"2013","journal-title":"Physiol. Behav."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.neulet.2017.01.015","article-title":"Melatonin produces a rapid onset and prolonged efficacy in reducing depression-like behaviors in adult rats exposed to chronic unpredictable mild stress","volume":"642","author":"Sun","year":"2017","journal-title":"Neurosci. Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/j.pharep.2016.04.003","article-title":"Melatonin and neurotrophins NT-3, BDNF, NGF in patients with varying levels of depression severity","volume":"68","author":"Just","year":"2016","journal-title":"Pharmacol. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.comppsych.2016.03.005","article-title":"Differential melatonin alterations in cerebrospinal fluid and serum of patients with major depressive disorder and bipolar disorder","volume":"68","author":"Bumb","year":"2016","journal-title":"Compr. Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Sundberg, I., Ramklint, M., Stridsberg, M., Papadopoulos, F.C., Ekselius, L., and Cunningham, J.L. (2016). Salivary Melatonin in Relation to Depressive Symptom Severity in Young Adults. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0152814"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/j.1600-079X.2010.00802.x","article-title":"Chronic treatment with melatonin stimulates dendrite maturation and complexity in adult hippocampal neurogenesis of mice","volume":"50","author":"Kempermann","year":"2011","journal-title":"J. Pineal Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.neulet.2012.09.045","article-title":"Melatonin supplementation delays the decline of adult hippocampal neurogenesis during normal aging of mice","volume":"530","year":"2012","journal-title":"Neurosci. Lett."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ramirez-Rodriguez, G.B., Olvera-Hernandez, S., Vega-Rivera, N.M., and Ortiz-Lopez, L. (2018). Melatonin Influences Structural Plasticity in the Axons of Granule Cells in the Dentate Gyrus of Balb\/C Mice. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20010073"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1460-9568.2004.03813.x","article-title":"Doublecortin expression levels in adult brain reflect neurogenesis","volume":"21","author":"Winner","year":"2005","journal-title":"Eur. J. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3376","DOI":"10.1523\/JNEUROSCI.4248-11.2012","article-title":"Gene expression profiling of neural stem cells and their neuronal progeny reveals IGF2 as a regulator of adult hippocampal neurogenesis","volume":"32","author":"Bracko","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Plumpe, T., Ehninger, D., Steiner, B., Klempin, F., Jessberger, S., Brandt, M., Romer, B., Rodriguez, G.R., Kronenberg, G., and Kempermann, G. (2006). Variability of doublecortin-associated dendrite maturation in adult hippocampal neurogenesis is independent of the regulation of precursor cell proliferation. BMC Neurosci., 7.","DOI":"10.1186\/1471-2202-7-77"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1038\/mp.2008.147","article-title":"Ageing abolishes the effects of fluoxetine on neurogenesis","volume":"14","author":"Wuertinger","year":"2009","journal-title":"Mol. Psychiatry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.ejphar.2008.06.070","article-title":"Combination therapy of imipramine and melatonin: Additive antidepressant effect in mouse forced swimming test","volume":"591","author":"Ergun","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.2174\/138161209788168056","article-title":"Melatonin receptor agonist agomelatine: A new drug for treating unipolar depression","volume":"15","author":"Bourin","year":"2009","journal-title":"Curr. Pharm. Des."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1016\/j.jpsychires.2012.08.013","article-title":"An exploratory study of combination buspirone and melatonin SR in major depressive disorder (MDD): A possible role for neurogenesis in drug discovery","volume":"46","author":"Fava","year":"2013","journal-title":"J. Psychiatr. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1111\/jpi.12136","article-title":"Melatonin synergizes with citalopram to induce antidepressant-like behavior and to promote hippocampal neurogenesis in adult mice","volume":"56","year":"2014","journal-title":"J. Pineal Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1002\/(SICI)1098-1063(1998)8:6<608::AID-HIPO3>3.0.CO;2-7","article-title":"Functional differentiation in the hippocampus","volume":"8","author":"Moser","year":"1998","journal-title":"Hippocampus"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9697","DOI":"10.1073\/pnas.92.21.9697","article-title":"Spatial learning with a minislab in the dorsal hippocampus","volume":"92","author":"Moser","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"10825","DOI":"10.1073\/pnas.152112399","article-title":"Reduced fear expression after lesions of the ventral hippocampus","volume":"99","author":"Kjelstrup","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.neubiorev.2004.03.004","article-title":"Regional dissociations within the hippocampus\u2014Memory and anxiety","volume":"28","author":"Bannerman","year":"2004","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1037\/0735-7044.118.1.63","article-title":"Amygdala and ventral hippocampus contribute differentially to mechanisms of fear and anxiety","volume":"118","author":"McHugh","year":"2004","journal-title":"Behav. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1111\/j.1460-9568.2006.04754.x","article-title":"Effects of lesions to the dorsal and ventral hippocampus on defensive behaviors in rats","volume":"23","author":"Pentkowski","year":"2006","journal-title":"Eur. J. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1002\/hipo.22134","article-title":"Region-dependent and stage-specific effects of stress, environmental enrichment, and antidepressant treatment on hippocampal neurogenesis","volume":"23","author":"Tanti","year":"2013","journal-title":"Hippocampus"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/j.1600-079X.2008.00568.x","article-title":"Delayed melatonin administration promotes neuronal survival, neurogenesis and motor recovery, and attenuates hyperactivity and anxiety after mild focal cerebral ischemia in mice","volume":"45","author":"Kilic","year":"2008","journal-title":"J. Pineal Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/j.1600-079X.2008.00632.x","article-title":"Cranial irradiation-induced inhibition of neurogenesis in hippocampal dentate gyrus of adult mice: Attenuation by melatonin pretreatment","volume":"46","author":"Manda","year":"2009","journal-title":"J. Pineal Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.neuroscience.2007.04.054","article-title":"Both increases in immature dentate neuron number and decreases of immobility time in the forced swim test occurred in parallel after environmental enrichment of mice","volume":"147","author":"Rueda","year":"2007","journal-title":"Neuroscience"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.psyneuen.2015.03.022","article-title":"Effect of sub-optimal doses of fluoxetine plus estradiol on antidepressant-like behavior and hippocampal neurogenesis in ovariectomized rats","volume":"57","year":"2015","journal-title":"Psychoneuroendocrinology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1139\/cjpp-2018-0612","article-title":"Melatonin treatment affects changes in adrenal gene expression of catecholamine biosynthesizing enzymes and norepinephrine transporter in the rat model of chronic-stress-induced depression","volume":"97","author":"Stefanovic","year":"2019","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1111\/j.1600-079X.2008.00611.x","article-title":"Space radiation-induced inhibition of neurogenesis in the hippocampal dentate gyrus and memory impairment in mice: Ameliorative potential of the melatonin metabolite, AFMK","volume":"45","author":"Manda","year":"2008","journal-title":"J. Pineal Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.1097\/01.yic.0000277958.83475.d5","article-title":"Evidence of agomelatine\u2019s antidepressant efficacy: The key points","volume":"22","author":"Eser","year":"2007","journal-title":"Int. Clin. Psychopharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1017\/S1461145711000356","article-title":"Beneficial behavioural and neurogenic effects of agomelatine in a model of depression\/anxiety","volume":"15","author":"Rainer","year":"2012","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/jpi.12023","article-title":"Melatonin potentiates running wheel-induced neurogenesis in the dentate gyrus of adult C3H\/HeN mice hippocampus","volume":"54","author":"Liu","year":"2013","journal-title":"J. Pineal Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e1101","DOI":"10.1038\/tp.2017.68","article-title":"Depletion of adult neurogenesis using the chemotherapy drug temozolomide in mice induces behavioural and biological changes relevant to depression","volume":"7","author":"Egeland","year":"2017","journal-title":"Transl. Psychiatry"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"10409","DOI":"10.1073\/pnas.94.19.10409","article-title":"Genetic influence on neurogenesis in the dentate gyrus of adult mice","volume":"94","author":"Kempermann","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1111\/j.1601-183X.2010.00674.x","article-title":"Genetic influences on exercise-induced adult hippocampal neurogenesis across 12 divergent mouse strains","volume":"10","author":"Clark","year":"2011","journal-title":"Genes Brain Behav."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1177\/074873098129000228","article-title":"Daily variations in pineal melatonin concentrations in inbred and outbred mice","volume":"13","author":"Malan","year":"1998","journal-title":"J. Biol. Rhythm."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/j.1600-079X.2006.00408.x","article-title":"Melatonin induces neuritogenesis at early stages in N1E-115 cells through actin rearrangements via activation of protein kinase C and Rho-associated kinase","volume":"42","author":"Bellon","year":"2007","journal-title":"J. Pineal Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0197-0186(01)00021-3","article-title":"Melatonin activates PKC-alpha but not PKC-epsilon in N1E-115 cells","volume":"39","author":"Hernandez","year":"2001","journal-title":"Neurochem. Int."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1111\/j.1600-079X.2006.00404.x","article-title":"Melatonin increases stress fibers and focal adhesions in MDCK cells: Participation of Rho-associated kinase and protein kinase C","volume":"42","year":"2007","journal-title":"J. Pineal Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1007\/s00702-008-0066-z","article-title":"Role of melatonin receptors in the effects of melatonin on BDNF and neuroprotection in mouse cerebellar neurons","volume":"115","author":"Imbesi","year":"2008","journal-title":"J. Neural Transm."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/jpi.12248","article-title":"Melatonin attenuates impairments of structural hippocampal neuroplasticity in OXYS rats during active progression of Alzheimer\u2019s disease-like pathology","volume":"59","author":"Stefanova","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1007\/s10571-016-0450-4","article-title":"Melatonin Increases Oligodendrocyte Differentiation in Cultured Neural Stem Cells","volume":"37","author":"Ghareghani","year":"2017","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1159\/000014636","article-title":"Pharmacology and physiology of melatonin in the reduction of oxidative stress in vivo","volume":"9","author":"Reiter","year":"2000","journal-title":"Biol. Signals Recept."},{"key":"ref_62","first-page":"327","article-title":"Behavioral despair in mice: A primary screening test for antidepressants","volume":"229","author":"Porsolt","year":"1977","journal-title":"Arch. Int. Pharmacodyn. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/266730a0","article-title":"Depression: A new animal model sensitive to antidepressant treatments","volume":"266","author":"Porsolt","year":"1977","journal-title":"Nature"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/0014-2999(78)90118-8","article-title":"Behavioural despair in rats: A new model sensitive to antidepressant treatments","volume":"47","author":"Porsolt","year":"1978","journal-title":"Eur. J. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1242\/dev.00203","article-title":"Early determination and long-term persistence of adult-generated new neurons in the hippocampus of mice","volume":"130","author":"Kempermann","year":"2003","journal-title":"Development"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/5\/1724\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:03:46Z","timestamp":1760173426000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/5\/1724"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,3]]},"references-count":65,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["ijms21051724"],"URL":"https:\/\/doi.org\/10.3390\/ijms21051724","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,3]]}}}