{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T10:41:32Z","timestamp":1762252892805,"version":"build-2065373602"},"reference-count":72,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2018,12,25]],"date-time":"2018-12-25T00:00:00Z","timestamp":1545696000000},"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>Melatonin, the main product synthesized by the pineal gland, acts as a regulator of the generation of new neurons in the dentate gyrus (DG). Newborn neurons buffer the deleterious effects of stress and are involved in learning and memory processes. Furthermore, melatonin, through the regulation of the cytoskeleton, favors dendrite maturation of newborn neurons. Moreover, newborn neurons send their axons via the mossy fiber tract to Cornu Ammonis 3 (CA3) region to form synapses with pyramidal neurons. Thus, axons of newborn cells contribute to the mossy fiber projection and their plasticity correlates with better performance in several behavioral tasks. Thus, in this study, we analyzed the impact of exogenous melatonin (8 mg\/kg) administered daily for one- or six-months on the structural plasticity of infrapyramidal- and suprapyramidal mossy fiber projection of granule cells in the DG in male Balb\/C mice. We analyzed the mossy fiber projection through the staining of calbindin, that is a calcium-binding protein localized in dendrites and axons. We first found an increase in the number of calbindin-positive cells in the granular cell layer in the DG (11%, 33%) after treatment. Futhermore, we found an increase in the volume of suprapyramidal (&gt;135%, 59%) and infrapyramidal (&gt;128%, 36%) mossy fiber projection of granule neurons in the DG after treatment. We also found an increase in the volume of CA3 region (&gt;146%, 33%) after treatment, suggesting that melatonin modulates the structural plasticity of the mossy fiber projection to establish functional synapses in the hippocampus. Together, the data suggest that, in addition to the previously reported effects of melatonin on the generation of new neurons and its antidepressant like effects, melatonin also modulates the structural plasticity of axons in granule cells in the DG.<\/jats:p>","DOI":"10.3390\/ijms20010073","type":"journal-article","created":{"date-parts":[[2018,12,26]],"date-time":"2018-12-26T04:29:54Z","timestamp":1545798594000},"page":"73","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Melatonin Influences Structural Plasticity in the Axons of Granule Cells in the Dentate Gyrus of Balb\/C Mice"],"prefix":"10.3390","volume":"20","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":"Laboratorio de Neurogenesis, Subidrecci\u00f3n de Investigaciones Cl\u00ednicas, Instituto Nacional de Psiquiatr\u00eda \u201cRam\u00f3n de la Fuente Mu\u00f1iz\u201d, Calzada M\u00e9xico-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, M\u00e9xico City C.P. 14370, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0188-902X","authenticated-orcid":false,"given":"Sandra","family":"Olvera-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurogenesis, Subidrecci\u00f3n de Investigaciones Cl\u00ednicas, Instituto Nacional de Psiquiatr\u00eda \u201cRam\u00f3n de la Fuente Mu\u00f1iz\u201d, Calzada M\u00e9xico-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, M\u00e9xico City C.P. 14370, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelly Maritza","family":"Vega-Rivera","sequence":"additional","affiliation":[{"name":"Laboratorio de Neuropsicofarmacolog\u00eda, Direcci\u00f3n de Neurociencias, Instituto Nacional de Psiquiatr\u00eda \u201cRam\u00f3n de la Fuente Mu\u00f1iz\u201d, Calzada M\u00e9xico-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, M\u00e9xico City C.P. 14370, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo","family":"Ortiz-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurogenesis, Subidrecci\u00f3n de Investigaciones Cl\u00ednicas, Instituto Nacional de Psiquiatr\u00eda \u201cRam\u00f3n de la Fuente Mu\u00f1iz\u201d, Calzada M\u00e9xico-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, M\u00e9xico City C.P. 14370, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.sleep.2007.10.007","article-title":"Melatonin receptors: Role on sleep and circadian rhythm regulation","volume":"8","author":"Dubocovich","year":"2007","journal-title":"Sleep Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1385\/ENDO:27:2:101","article-title":"Functional MT1 and MT2 melatonin receptors in mammals","volume":"27","author":"Dubocovich","year":"2005","journal-title":"Endocrine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/BF01923944","article-title":"Calmodulin mediates melatonin cytoskeletal effects","volume":"49","year":"1993","journal-title":"Experientia"},{"key":"ref_4","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. 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