{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:42:29Z","timestamp":1790487749375,"version":"4.1.0"},"reference-count":73,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T00:00:00Z","timestamp":1524009600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T00:00:00Z","timestamp":1524009600000},"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":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To survive in temperate latitudes, species rely on the photoperiod to synchronize their physiological functions, including reproduction, with the predictable changes in the environment. In sheep, exposure to decreasing day length reactivates the hypothalamo-pituitary-gonadal axis, while during increasing day length, animals enter a period of sexual rest. Neural stem cells have been detected in the sheep hypothalamus and hypothalamic neurogenesis was found to respond to the photoperiod. However, the physiological relevance of this seasonal adult neurogenesis is still unexplored. This longitudinal study, therefore aimed to thoroughly characterize photoperiod-stimulated neurogenesis and to investigate whether the hypothalamic adult born-cells were involved in the seasonal timing of reproduction. Results showed that time course of cell proliferation reached a peak in the middle of the period of sexual activity, corresponding to decreasing day length period. This enhancement was suppressed when animals were deprived of seasonal time cues by pinealectomy, suggesting a role of melatonin in the seasonal regulation of cell proliferation. Furthermore, when the mitotic blocker cytosine-b-D-arabinofuranoside was administered centrally, the timing of seasonal reproduction was affected. Overall, our findings link the cyclic increase in hypothalamic neurogenesis to seasonal reproduction and suggest that photoperiod-regulated hypothalamic neurogenesis plays a substantial role in seasonal reproductive physiology.<\/jats:p>","DOI":"10.1038\/s41598-018-24381-4","type":"journal-article","created":{"date-parts":[[2018,4,12]],"date-time":"2018-04-12T12:13:39Z","timestamp":1523535219000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Pineal-dependent increase of hypothalamic neurogenesis contributes to the timing of seasonal reproduction in sheep"],"prefix":"10.1038","volume":"8","author":[{"given":"Martine","family":"Batailler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Chesneau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Derouet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucile","family":"Butruille","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Segura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliette","family":"Cogni\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00eblle","family":"Dupont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Pillon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9496-0517","authenticated-orcid":false,"given":"Martine","family":"Migaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,4,18]]},"reference":[{"key":"24381_CR1","doi-asserted-by":"crossref","unstructured":"Hazlerigg, D. & Simonneaux, V. In Physiology of reproduction Vol. 2 (eds Knobil & Neill) 1575\u20131604 (Academic press, 2014).","DOI":"10.1016\/B978-0-12-397175-3.00034-X"},{"key":"24381_CR2","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1210\/edrv-12-2-151","volume":"12","author":"RJ Reiter","year":"1991","unstructured":"Reiter, R. J. Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocr Rev 12, 151\u2013180, https:\/\/doi.org\/10.1210\/edrv-12-2-151 (1991).","journal-title":"Endocr Rev"},{"key":"24381_CR3","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1111\/j.1600-079X.1993.tb00903.x","volume":"15","author":"TJ Bartness","year":"1993","unstructured":"Bartness, T. J., Powers, J. B., Hastings, M. H., Bittman, E. L. & Goldman, B. D. The timed infusion paradigm for melatonin delivery: what has it taught us about the melatonin signal, its reception, and the photoperiodic control of seasonal responses? Journal of pineal research 15, 161\u2013190 (1993).","journal-title":"Journal of pineal research"},{"key":"24381_CR4","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1177\/074873001129001980","volume":"16","author":"BD Goldman","year":"2001","unstructured":"Goldman, B. D. Mammalian photoperiodic system: formal properties and neuroendocrine mechanisms of photoperiodic time measurement. Journal of biological rhythms 16, 283\u2013301 (2001).","journal-title":"Journal of biological rhythms"},{"key":"24381_CR5","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.ygcen.2005.11.004","volume":"146","author":"SM Hiebert","year":"2006","unstructured":"Hiebert, S. M., Green, S. A. & Yellon, S. M. Daily timed melatonin feedings mimic effects of short days on testis regression and cortisol in circulation in Siberian hamsters. Gen Comp Endocrinol 146, 211\u2013216, https:\/\/doi.org\/10.1016\/j.ygcen.2005.11.004 (2006).","journal-title":"Gen Comp Endocrinol"},{"key":"24381_CR6","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/j.neuroscience.2013.06.020","volume":"248","author":"JC Walton","year":"2013","unstructured":"Walton, J. C., Chen, Z., Travers, J. B. & Nelson, R. J. Exogenous melatonin reproduces the effects of short day lengths on hippocampal function in male white-footed mice, Peromyscus leucopus. Neuroscience 248, 403\u2013413, https:\/\/doi.org\/10.1016\/j.neuroscience.2013.06.020 (2013).","journal-title":"Neuroscience"},{"key":"24381_CR7","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1210\/edrv-1-2-109","volume":"1","author":"RJ Reiter","year":"1980","unstructured":"Reiter, R. J. The pineal and its hormones in the control of reproduction in mammals. Endocr Rev 1, 109\u2013131, https:\/\/doi.org\/10.1210\/edrv-1-2-109 (1980).","journal-title":"Endocr Rev"},{"key":"24381_CR8","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1177\/074873001129002051","volume":"16","author":"B Malpaux","year":"2001","unstructured":"Malpaux, B., Migaud, M., Tricoire, H. & Chemineau, P. Biology of mammalian photoperiodism and the critical role of the pineal gland and melatonin. Journal of biological rhythms 16, 336\u2013347 (2001).","journal-title":"Journal of biological rhythms"},{"key":"24381_CR9","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.cell.2008.01.033","volume":"132","author":"C Zhao","year":"2008","unstructured":"Zhao, C., Deng, W. & Gage, F. H. Mechanisms and functional implications of adult neurogenesis. Cell 132, 645\u2013660, https:\/\/doi.org\/10.1016\/j.cell.2008.01.033 (2008).","journal-title":"Cell"},{"key":"24381_CR10","doi-asserted-by":"publisher","first-page":"2042","DOI":"10.1111\/j.1460-9568.2010.07521.x","volume":"32","author":"M Migaud","year":"2010","unstructured":"Migaud, M. et al. Emerging new sites for adult neurogenesis in the mammalian brain: a comparative study between the hypothalamus and the classical neurogenic zones. The European journal of neuroscience 32, 2042\u20132052, https:\/\/doi.org\/10.1111\/j.1460-9568.2010.07521.x (2010).","journal-title":"The European journal of neuroscience"},{"key":"24381_CR11","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.yfrne.2014.11.004","volume":"37","author":"M Migaud","year":"2015","unstructured":"Migaud, M., Butrille, L. & Batailler, M. Seasonal regulation of structural plasticity and neurogenesis in the adult mammalian brain: focus on the sheep hypothalamus. Frontiers in neuroendocrinology 37, 146\u2013157, https:\/\/doi.org\/10.1016\/j.yfrne.2014.11.004 (2015).","journal-title":"Frontiers in neuroendocrinology"},{"key":"24381_CR12","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/j.ijdevneu.2012.07.003","volume":"30","author":"DA Lee","year":"2012","unstructured":"Lee, D. A. & Blackshaw, S. Functional implications of hypothalamic neurogenesis in the adult mammalian brain. Int J Dev Neurosci 30, 615\u2013621 (2012).","journal-title":"Int J Dev Neurosci"},{"key":"24381_CR13","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1007\/s10571-014-0058-5","volume":"34","author":"E Rojczyk-Golebiewska","year":"2014","unstructured":"Rojczyk-Golebiewska, E., Palasz, A. & Wiaderkiewicz, R. Hypothalamic subependymal niche: a novel site of the adult neurogenesis. Cell Mol Neurobiol 34, 631\u2013642, https:\/\/doi.org\/10.1007\/s10571-014-0058-5 (2014).","journal-title":"Cell Mol Neurobiol"},{"key":"24381_CR14","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1002\/cne.21492","volume":"505","author":"MV Kokoeva","year":"2007","unstructured":"Kokoeva, M. V., Yin, H. & Flier, J. S. Evidence for constitutive neural cell proliferation in the adult murine hypothalamus. The Journal of comparative neurology 505, 209\u2013220, https:\/\/doi.org\/10.1002\/cne.21492 (2007).","journal-title":"The Journal of comparative neurology"},{"key":"24381_CR15","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1172\/JCI43134","volume":"122","author":"DE McNay","year":"2012","unstructured":"McNay, D. E., Brian\u00e7on, N., Kokoeva, M. V., Maratos-Flier, E. & Flier, J. S. Remodeling of the arcuate nucleus energy-balance circuit is inhibited in obese mice. J Clin Invest 122, 142\u2013152 (2012).","journal-title":"J Clin Invest"},{"key":"24381_CR16","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.1002\/cne.23514","volume":"522","author":"M Batailler","year":"2014","unstructured":"Batailler, M. et al. DCX-expressing cells in the vicinity of the hypothalamic neurogenic niche: a comparative study between mouse, sheep, and human tissues. J Comp Neurol 522, 1966\u20131985 (2014).","journal-title":"J Comp Neurol"},{"key":"24381_CR17","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1177\/0748730411420062","volume":"26","author":"M Migaud","year":"2011","unstructured":"Migaud, M., Batailler, M., Pillon, D., Franceschini, I. & Malpaux, B. Seasonal changes in cell proliferation in the adult sheep brain and pars tuberalis. Journal of biological rhythms 26, 486\u2013496, https:\/\/doi.org\/10.1177\/0748730411420062 (2011).","journal-title":"Journal of biological rhythms"},{"key":"24381_CR18","doi-asserted-by":"publisher","first-page":"3301","DOI":"10.1007\/s00429-015-1101-0","volume":"221","author":"M Batailler","year":"2016","unstructured":"Batailler, M., Derouet, L., Butruille, L. & Migaud, M. Sensitivity to the photoperiod and potential migratory features of neuroblasts in the adult sheep hypothalamus. Brain structure & function 221, 3301\u20133314, https:\/\/doi.org\/10.1007\/s00429-015-1101-0 (2016).","journal-title":"Brain structure & function"},{"key":"24381_CR19","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.1017\/S1751731111000668","volume":"5","author":"A Chanvallon","year":"2011","unstructured":"Chanvallon, A. et al. New insights into the influence of breed and time of the year on the response of ewes to the \u2018ram effect\u2019. Animal: an international journal of animal bioscience 5, 1594\u20131604, https:\/\/doi.org\/10.1017\/S1751731111000668 (2011).","journal-title":"Animal: an international journal of animal bioscience"},{"key":"24381_CR20","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1016\/S0306-4522(98)00345-5","volume":"89","author":"LA Galea","year":"1999","unstructured":"Galea, L. A. & McEwen, B. S. Sex and seasonal differences in the rate of cell proliferation in the dentate gyrus of adult wild meadow voles. Neuroscience 89, 955\u2013964 (1999).","journal-title":"Neuroscience"},{"key":"24381_CR21","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/S0304-3940(03)00546-9","volume":"346","author":"BK Ormerod","year":"2003","unstructured":"Ormerod, B. K. & Galea, L. A. Reproductive status influences the survival of new cells in the dentate gyrus of adult male meadow voles. Neuroscience letters 346, 25\u201328 (2003).","journal-title":"Neuroscience letters"},{"key":"24381_CR22","doi-asserted-by":"publisher","first-page":"1710","DOI":"10.1111\/j.1460-9568.2008.06133.x","volume":"27","author":"K Bartkowska","year":"2008","unstructured":"Bartkowska, K., Djavadian, R. L., Taylor, J. R. & Turlejski, K. Generation recruitment and death of brain cells throughout the life cycle of Sorex shrews (Lipotyphla). Eur J Neurosci 27, 1710\u20131721 (2008).","journal-title":"Eur J Neurosci"},{"key":"24381_CR23","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1002\/(SICI)1097-4695(19980905)36:3<410::AID-NEU8>3.0.CO;2-Z","volume":"36","author":"L Huang","year":"1998","unstructured":"Huang, L., DeVries, G. J. & Bittman, E. L. Photoperiod regulates neuronal bromodeoxyuridine labeling in the brain of a seasonally breeding mammal. Journal of neurobiology 36, 410\u2013420 (1998).","journal-title":"Journal of neurobiology"},{"key":"24381_CR24","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1006\/hbeh.2000.1630","volume":"39","author":"MT Smith","year":"2001","unstructured":"Smith, M. T., Pencea, V., Wang, Z., Luskin, M. B. & Insel, T. R. Increased number of BrdU-labeled neurons in the rostral migratory stream of the estrous prairie vole. Hormones and behavior 39, 11\u201321, https:\/\/doi.org\/10.1006\/hbeh.2000.1630 (2001).","journal-title":"Hormones and behavior"},{"key":"24381_CR25","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1016\/S0092-8674(00)80783-7","volume":"97","author":"F Doetsch","year":"1999","unstructured":"Doetsch, F., Caille, I., Lim, D. A., Garcia-Verdugo, J. M. & Alvarez-Buylla, A. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97, 703\u2013716 (1999).","journal-title":"Cell"},{"key":"24381_CR26","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1126\/science.1115360","volume":"310","author":"MV Kokoeva","year":"2005","unstructured":"Kokoeva, M. V., Yin, H. & Flier, J. S. Neurogenesis in the hypothalamus of adult mice: potential role in energy balance. Science 310, 679\u2013683, https:\/\/doi.org\/10.1126\/science.1115360 (2005).","journal-title":"Science"},{"key":"24381_CR27","doi-asserted-by":"publisher","first-page":"15245","DOI":"10.1523\/JNEUROSCI.3606-09.2009","volume":"29","author":"V Breton-Provencher","year":"2009","unstructured":"Breton-Provencher, V., Lemasson, M., Peralta, M. R. III & Saghatelyan, A. Interneurons produced in adulthood are required for the normal functioning of the olfactory bulb network and for the execution of selected olfactory behaviors. J Neurosci 29, 15245\u201315257, https:\/\/doi.org\/10.1523\/JNEUROSCI.3606-09.2009 (2009).","journal-title":"J Neurosci"},{"key":"24381_CR28","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1016\/j.neuroscience.2009.09.048","volume":"164","author":"S Dutheil","year":"2009","unstructured":"Dutheil, S., Brezun, J. M., Leonard, J., Lacour, M. & Tighilet, B. Neurogenesis and astrogenesis contribution to recovery of vestibular functions in the adult cat following unilateral vestibular neurectomy: cellular and behavioral evidence. Neuroscience 164, 1444\u20131456, https:\/\/doi.org\/10.1016\/j.neuroscience.2009.09.048 (2009).","journal-title":"Neuroscience"},{"key":"24381_CR29","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/j.cell.2004.07.025","volume":"118","author":"K Kozar","year":"2004","unstructured":"Kozar, K. et al. Mouse development and cell proliferation in the absence of D-cyclins. Cell 118, 477\u2013491, https:\/\/doi.org\/10.1016\/j.cell.2004.07.025 (2004).","journal-title":"Cell"},{"key":"24381_CR30","doi-asserted-by":"publisher","first-page":"548","DOI":"10.3109\/07420528.2012.754450","volume":"30","author":"DG Hazlerigg","year":"2013","unstructured":"Hazlerigg, D. G., Wyse, C. A., Dardente, H., Hanon, E. A. & Lincoln, G. A. Photoperiodic variation in CD45-positive cells and cell proliferation in the mediobasal hypothalamus of the Soay sheep. Chronobiol Int 30, 548\u2013558 (2013).","journal-title":"Chronobiol Int"},{"key":"24381_CR31","doi-asserted-by":"publisher","first-page":"1368","DOI":"10.1126\/science.7313697","volume":"214","author":"F Nottebohm","year":"1981","unstructured":"Nottebohm, F. A brain for all seasons: cyclical anatomical changes in song control nuclei of the canary brain. Science 214, 1368\u20131370 (1981).","journal-title":"Science"},{"key":"24381_CR32","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1126\/science.6474166","volume":"225","author":"JA Paton","year":"1984","unstructured":"Paton, J. A. & Nottebohm, F. N. Neurons generated in the adult brain are recruited into functional circuits. Science 225, 1046\u20131048 (1984).","journal-title":"Science"},{"key":"24381_CR33","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1098\/rstb.2009.0220","volume":"365","author":"DF Sherry","year":"2010","unstructured":"Sherry, D. F. & Hoshooley, J. S. Seasonal hippocampal plasticity in food-storing birds. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 365, 933\u2013943, https:\/\/doi.org\/10.1098\/rstb.2009.0220 (2010).","journal-title":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences"},{"key":"24381_CR34","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.bbr.2012.08.044","volume":"236","author":"DK Burger","year":"2013","unstructured":"Burger, D. K., Saucier, J. M. & Iwaniuk, A. N. & Saucier DM. Seasonal and sex differences in the hippocampus of a wild rodent. Behav Brain Res 236, 131\u2013138 (2013).","journal-title":"Behav Brain Res"},{"key":"24381_CR35","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1046\/j.1460-9568.2000.00949.x","volume":"12","author":"P Lavenex","year":"2000","unstructured":"Lavenex, P., Steele, M. A. & Jacobs, L. F. The seasonal pattern of cell proliferation and neuron number in the dentate gyrus of wild adult eastern grey squirrels. Eur J Neurosci 12, 643\u2013648 (2000).","journal-title":"Eur J Neurosci"},{"key":"24381_CR36","doi-asserted-by":"publisher","first-page":"e42743","DOI":"10.1371\/journal.pone.0042743","volume":"7","author":"JC Walton","year":"2012","unstructured":"Walton, J. C., Pyter, L. M., Weil, Z. M. & Nelson, R. J. Photoperiod mediated changes in olfactory bulb neurogenesis and olfactory behavior in male white-footed mice (Peromyscus leucopus). PLoS One 7, e42743 (2012).","journal-title":"PLoS One"},{"key":"24381_CR37","first-page":"835","volume":"166","author":"NL Wayne","year":"1990","unstructured":"Wayne, N. L., Malpaux, B. & Karsch, F. J. Photoperiodic requirements for timing onset and duration of the breeding season of the ewe: synchronization of an endogenous rhythm of reproduction. Journal of comparative physiology. A, Sensory, neural, and behavioral physiology 166, 835\u2013842 (1990).","journal-title":"Journal of comparative physiology. A, Sensory, neural, and behavioral physiology"},{"key":"24381_CR38","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1095\/biolreprod50.4.965","volume":"50","author":"CJ Woodfill","year":"1994","unstructured":"Woodfill, C. J., Wayne, N. L., Moenter, S. M. & Karsch, F. J. Photoperiodic synchronization of a circannual reproductive rhythm in sheep: identification of season-specific time cues. Biology of reproduction 50, 965\u2013976 (1994).","journal-title":"Biology of reproduction"},{"key":"24381_CR39","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.mce.2015.10.012","volume":"420","author":"J Chu","year":"2016","unstructured":"Chu, J. et al. Effects of melatonin and its analogues on neural stem cells. Molecular and cellular endocrinology 420, 169\u2013179, https:\/\/doi.org\/10.1016\/j.mce.2015.10.012 (2016).","journal-title":"Molecular and cellular endocrinology"},{"key":"24381_CR40","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1007\/s10571-007-9212-7","volume":"28","author":"X Kong","year":"2008","unstructured":"Kong, X. et al. Melatonin regulates the viability and differentiation of rat midbrain neural stem cells. Cell Mol Neurobiol 28, 569\u2013579, https:\/\/doi.org\/10.1007\/s10571-007-9212-7 (2008).","journal-title":"Cell Mol Neurobiol"},{"key":"24381_CR41","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/j.neuroscience.2014.06.026","volume":"275","author":"C Tocharus","year":"2014","unstructured":"Tocharus, C. et al. Melatonin enhances adult rat hippocampal progenitor cell proliferation via ERK signaling pathway through melatonin receptor. Neuroscience 275, 314\u2013321, https:\/\/doi.org\/10.1016\/j.neuroscience.2014.06.026 (2014).","journal-title":"Neuroscience"},{"key":"24381_CR42","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1111\/j.1600-079X.2010.00794.x","volume":"49","author":"A Sotthibundhu","year":"2010","unstructured":"Sotthibundhu, A., Phansuwan-Pujito, P. & Govitrapong, P. Melatonin increases proliferation of cultured neural stem cells obtained from adult mouse subventricular zone. Journal of pineal research 49, 291\u2013300, https:\/\/doi.org\/10.1111\/j.1600-079X.2010.00794.x (2010).","journal-title":"Journal of pineal research"},{"key":"24381_CR43","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1111\/j.1600-079X.2004.00157.x","volume":"37","author":"MJ Kim","year":"2004","unstructured":"Kim, M. J., Kim, H. K., Kim, B. S. & Yim, S. V. Melatonin increases cell proliferation in the dentate gyrus of maternally separated rats. Journal of pineal research 37, 193\u2013197, https:\/\/doi.org\/10.1111\/j.1600-079X.2004.00157.x (2004).","journal-title":"Journal of pineal research"},{"key":"24381_CR44","doi-asserted-by":"publisher","first-page":"2180","DOI":"10.1038\/npp.2009.46","volume":"34","author":"G Ramirez-Rodriguez","year":"2009","unstructured":"Ramirez-Rodriguez, G., Klempin, F., Babu, H., Benitez-King, G. & Kempermann, G. Melatonin modulates cell survival of new neurons in the hippocampus of adult mice. Neuropsychopharmacology 34, 2180\u20132191, https:\/\/doi.org\/10.1038\/npp.2009.46 (2009).","journal-title":"Neuropsychopharmacology"},{"key":"24381_CR45","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1111\/j.1600-079X.2010.00802.x","volume":"50","author":"G Ramirez-Rodriguez","year":"2011","unstructured":"Ramirez-Rodriguez, G., Ortiz-Lopez, L., Dominguez-Alonso, A., Benitez-King, G. A. & Kempermann, G. Chronic treatment with melatonin stimulates dendrite maturation and complexity in adult hippocampal neurogenesis of mice. Journal of pineal research 50, 29\u201337, https:\/\/doi.org\/10.1111\/j.1600-079X.2010.00802.x (2011).","journal-title":"Journal of pineal research"},{"key":"24381_CR46","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1111\/j.1600-079X.2011.00897.x","volume":"51","author":"R Crupi","year":"2011","unstructured":"Crupi, R. et al. Melatonin\u2019s stimulatory effect on adult hippocampal neurogenesis in mice persists after ovariectomy. Journal of pineal research 51, 353\u2013360, https:\/\/doi.org\/10.1111\/j.1600-079X.2011.00897.x (2011).","journal-title":"Journal of pineal research"},{"key":"24381_CR47","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1016\/j.biopsych.2005.11.025","volume":"59","author":"M Banasr","year":"2006","unstructured":"Banasr, M., Soumier, A., Hery, M., Mocaer, E. & Daszuta, A. Agomelatine, a new antidepressant, induces regional changes in hippocampal neurogenesis. Biol Psychiatry 59, 1087\u20131096, https:\/\/doi.org\/10.1016\/j.biopsych.2005.11.025 (2006).","journal-title":"Biol Psychiatry"},{"key":"24381_CR48","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-5-41","volume":"5","author":"LP Niles","year":"2004","unstructured":"Niles, L. P. et al. Neural stem cells express melatonin receptors and neurotrophic factors: colocalization of the MT1 receptor with neuronal and glial markers. BMC Neurosci 5, 41, https:\/\/doi.org\/10.1186\/1471-2202-5-41 (2004).","journal-title":"BMC Neurosci"},{"key":"24381_CR49","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1111\/j.1460-9568.2010.07220.x","volume":"31","author":"M P\u00e9rez-Mart\u00edn","year":"2010","unstructured":"P\u00e9rez-Mart\u00edn, M. et al. IGF-I stimulates neurogenesis in the hypothalamus of adult rats. Eur J Neurosci 31, 1533\u20131548 (2010).","journal-title":"Eur J Neurosci"},{"key":"24381_CR50","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1002\/cne.21492","volume":"505","author":"MV Kokoeva","year":"2007","unstructured":"Kokoeva, M. V., Yin, H. & Flier, J. S. Evidence for constitutive neural cell proliferation in the adult murine hypothalamus. J Comp Neurol 505, 209\u2013220 (2007).","journal-title":"J Comp Neurol"},{"key":"24381_CR51","doi-asserted-by":"publisher","first-page":"6170","DOI":"10.1523\/JNEUROSCI.2437-12.2013","volume":"33","author":"N Haan","year":"2013","unstructured":"Haan, N. et al. Fgf10-expressing tanycytes add new neurons to the appetite\/energy-balance regulating centers of the postnatal and adult hypothalamus. The Journal of neuroscience: the official journal of the Society for Neuroscience 33, 6170\u20136180, https:\/\/doi.org\/10.1523\/JNEUROSCI.2437-12.2013 (2013).","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"key":"24381_CR52","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.expneurol.2004.12.021","volume":"192","author":"Y Xu","year":"2005","unstructured":"Xu, Y. et al. Neurogenesis in the ependymal layer of the adult rat 3rd ventricle. Experimental neurology 192, 251\u2013264, https:\/\/doi.org\/10.1016\/j.expneurol.2004.12.021 (2005).","journal-title":"Experimental neurology"},{"key":"24381_CR53","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1038\/nn.3079","volume":"15","author":"DA Lee","year":"2012","unstructured":"Lee, D. A. et al. Tanycytes of the hypothalamic median eminence form a diet-responsive neurogenic niche. Nature neuroscience 15, 700\u2013702, https:\/\/doi.org\/10.1038\/nn.3079 (2012).","journal-title":"Nature neuroscience"},{"key":"24381_CR54","doi-asserted-by":"crossref","unstructured":"Robins, S. C. et al. \u03b1-Tanycytes of the adult hypothalamic third ventricle include distinct populations of FGF-responsive neural progenitors. Nat Commun 4 (2013).","DOI":"10.1038\/ncomms3049"},{"key":"24381_CR55","doi-asserted-by":"publisher","first-page":"10434","DOI":"10.1523\/JNEUROSCI.2831-08.2008","volume":"28","author":"L Dimou","year":"2008","unstructured":"Dimou, L., Simon, C., Kirchhoff, F., Takebayashi, H. & Gotz, M. Progeny of Olig2-expressing progenitors in the gray and white matter of the adult mouse cerebral cortex. J Neurosci 28, 10434\u201310442, https:\/\/doi.org\/10.1523\/JNEUROSCI.2831-08.2008 (2008).","journal-title":"J Neurosci"},{"key":"24381_CR56","doi-asserted-by":"publisher","first-page":"1735","DOI":"10.1002\/glia.22554","volume":"61","author":"SC Robins","year":"2013","unstructured":"Robins, S. C. et al. Extensive regenerative plasticity among adult NG2-glia populations is exclusively based on self-renewal. Glia 61, 1735\u20131747, https:\/\/doi.org\/10.1002\/glia.22554 (2013).","journal-title":"Glia"},{"key":"24381_CR57","doi-asserted-by":"publisher","first-page":"e78236","DOI":"10.1371\/journal.pone.0078236","volume":"8","author":"SC Robins","year":"2013","unstructured":"Robins, S. C. et al. Evidence for NG2-glia derived, adult-born functional neurons in the hypothalamus. PLoS One 8, e78236, https:\/\/doi.org\/10.1371\/journal.pone.0078236 (2013).","journal-title":"PLoS One"},{"key":"24381_CR58","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/j.cmet.2016.04.013","volume":"23","author":"T Djogo","year":"2016","unstructured":"Djogo, T. et al. Adult NG2-Glia Are Required for Median Eminence-Mediated Leptin Sensing and Body Weight Control. Cell metabolism 23, 797\u2013810, https:\/\/doi.org\/10.1016\/j.cmet.2016.04.013 (2016).","journal-title":"Cell metabolism"},{"key":"24381_CR59","doi-asserted-by":"publisher","first-page":"157","DOI":"10.3389\/fnins.2014.00157","volume":"8","author":"DA Lee","year":"2014","unstructured":"Lee, D. A. et al. Dietary and sex-specific factors regulate hypothalamic neurogenesis in young adult mice. Front Neurosci 8, 157 (2014).","journal-title":"Front Neurosci"},{"key":"24381_CR60","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1002\/cne.23169","volume":"521","author":"M Brus","year":"2013","unstructured":"Brus, M. et al. Dynamics of olfactory and hippocampal neurogenesis in adult sheep. The Journal of comparative neurology 521, 169\u2013188, https:\/\/doi.org\/10.1002\/cne.23169 (2013).","journal-title":"The Journal of comparative neurology"},{"key":"24381_CR61","doi-asserted-by":"publisher","first-page":"2677","DOI":"10.1096\/fj.13-229559","volume":"27","author":"P Klosen","year":"2013","unstructured":"Klosen, P., Sebert, M. E., Rasri, K., Laran-Chich, M. P. & Simonneaux, V. TSH restores a summer phenotype in photoinhibited mammals via the RF-amides RFRP3 and kisspeptin. FASEB journal: official publication of the Federation of American Societies for Experimental Biology 27, 2677\u20132686, https:\/\/doi.org\/10.1096\/fj.13-229559 (2013).","journal-title":"FASEB journal: official publication of the Federation of American Societies for Experimental Biology"},{"key":"24381_CR62","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1210\/en.2011-1110","volume":"153","author":"T Ubuka","year":"2012","unstructured":"Ubuka, T. et al. Identification, expression, and physiological functions of Siberian hamster gonadotropin-inhibitory hormone. Endocrinology 153, 373\u2013385, https:\/\/doi.org\/10.1210\/en.2011-1110 (2012).","journal-title":"Endocrinology"},{"key":"24381_CR63","doi-asserted-by":"publisher","first-page":"5811","DOI":"10.1210\/en.2008-0575","volume":"149","author":"IJ Clarke","year":"2008","unstructured":"Clarke, I. J. et al. Potent action of RFamide-related peptide-3 on pituitary gonadotropes indicative of a hypophysiotropic role in the negative regulation of gonadotropin secretion. Endocrinology 149, 5811\u20135821, https:\/\/doi.org\/10.1210\/en.2008-0575 (2008).","journal-title":"Endocrinology"},{"key":"24381_CR64","doi-asserted-by":"publisher","first-page":"5770","DOI":"10.1210\/en.2008-0581","volume":"149","author":"JT Smith","year":"2008","unstructured":"Smith, J. T. et al. Variation in kisspeptin and RFamide-related peptide (RFRP) expression and terminal connections to gonadotropin-releasing hormone neurons in the brain: a novel medium for seasonal breeding in the sheep. Endocrinology 149, 5770\u20135782, https:\/\/doi.org\/10.1210\/en.2008-0581 (2008).","journal-title":"Endocrinology"},{"key":"24381_CR65","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1111\/j.1365-2826.2012.02283.x","volume":"24","author":"A Caraty","year":"2012","unstructured":"Caraty, A. et al. RF9 powerfully stimulates gonadotrophin secretion in the ewe: evidence for a seasonal threshold of sensitivity. J Neuroendocrinol 24, 725\u2013736, https:\/\/doi.org\/10.1111\/j.1365-2826.2012.02283.x (2012).","journal-title":"J Neuroendocrinol"},{"key":"24381_CR66","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1196\/annals.1298.027","volume":"1016","author":"F Nottebohm","year":"2004","unstructured":"Nottebohm, F. The road we travelled: discovery, choreography, and significance of brain replaceable neurons. Ann N Y Acad Sci 1016, 628\u2013658, https:\/\/doi.org\/10.1196\/annals.1298.027 (2004).","journal-title":"Ann N Y Acad Sci"},{"key":"24381_CR67","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1111\/j.1600-079X.2006.00370.x","volume":"41","author":"JC Thiery","year":"2006","unstructured":"Thiery, J. C. et al. Concentrations of estradiol in ewe cerebrospinal fluid are modulated by photoperiod through pineal-dependent mechanisms. Journal of pineal research 41, 306\u2013312, https:\/\/doi.org\/10.1111\/j.1600-079X.2006.00370.x (2006).","journal-title":"Journal of pineal research"},{"key":"24381_CR68","unstructured":"Cogni\u00e9, J. & Migaud, M. In Step by step experimental pinealectomy techniques in animals for researchers (ed Turgut, M.) Ch. 7, 137\u2013151 (NOVA Science Publishers, 2013)."},{"key":"24381_CR69","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1530\/jrf.0.1010625","volume":"101","author":"B Malpaux","year":"1994","unstructured":"Malpaux, B., Daveau, A., Maurice, F., Locatelli, A. & Thiery, J. C. Evidence that melatonin binding sites in the pars tuberalis do not mediate the photoperiodic actions of melatonin on LH and prolactin secretion in ewes. Journal of reproduction and fertility 101, 625\u2013632 (1994).","journal-title":"Journal of reproduction and fertility"},{"key":"24381_CR70","doi-asserted-by":"publisher","first-page":"3230","DOI":"10.1210\/endo.136.8.7628356","volume":"136","author":"DC Skinner","year":"1995","unstructured":"Skinner, D. C., Malpaux, B., Delaleu, B. & Caraty, A. Luteinizing hormone (LH)-releasing hormone in third ventricular cerebrospinal fluid of the ewe: correlation with LH pulses and the LH surge. Endocrinology 136, 3230\u20133237, https:\/\/doi.org\/10.1210\/endo.136.8.7628356 (1995).","journal-title":"Endocrinology"},{"key":"24381_CR71","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-5-46","volume":"5","author":"M Batailler","year":"2004","unstructured":"Batailler, M., Caraty, A., Malpaux, B. & Tillet, Y. Neuroanatomical organization of gonadotropin-releasing hormone neurons during the oestrus cycle in the ewe. BMC neuroscience 5, 46, https:\/\/doi.org\/10.1186\/1471-2202-5-46 (2004).","journal-title":"BMC neuroscience"},{"key":"24381_CR72","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1095\/biolreprod.110.087023","volume":"84","author":"L Tosca","year":"2011","unstructured":"Tosca, L. et al. Metformin decreases GnRH- and activin-induced gonadotropin secretion in rat pituitary cells: potential involvement of adenosine 5\u2032 monophosphate-activated protein kinase (PRKA). Biology of reproduction 84, 351\u2013362, https:\/\/doi.org\/10.1095\/biolreprod.110.087023 (2011).","journal-title":"Biology of reproduction"},{"key":"24381_CR73","doi-asserted-by":"publisher","DOI":"10.1186\/1477-5956-10-56","volume":"10","author":"H Guo","year":"2012","unstructured":"Guo, H. et al. An efficient procedure for protein extraction from formalin-fixed, paraffin-embedded tissues for reverse phase protein arrays. Proteome science 10, 56, https:\/\/doi.org\/10.1186\/1477-5956-10-56 (2012).","journal-title":"Proteome science"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-24381-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-24381-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-24381-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T23:14:29Z","timestamp":1720221269000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-24381-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,18]]},"references-count":73,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["24381"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-24381-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,18]]},"assertion":[{"value":"17 November 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 April 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"6188"}}