{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:15:52Z","timestamp":1790140552047,"version":"4.0.1"},"reference-count":78,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,2,4]],"date-time":"2019-02-04T00:00:00Z","timestamp":1549238400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,2,4]],"date-time":"2019-02-04T00:00:00Z","timestamp":1549238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001843","name":"DST | Science and Engineering Research Board","doi-asserted-by":"publisher","award":["PDF\/2016\/000670"],"award-info":[{"award-number":["PDF\/2016\/000670"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001843","name":"DST | Science and Engineering Research Board","doi-asserted-by":"publisher","award":["PDF\/2016\/000670"],"award-info":[{"award-number":["PDF\/2016\/000670"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology","doi-asserted-by":"publisher","award":["BT\/PR16164\/NER\/95\/88\/2015"],"award-info":[{"award-number":["BT\/PR16164\/NER\/95\/88\/2015"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"name":"DST PURSE-II, UGC RN, UGC-SAP at the level of DRS-I, (UPE-II, JNU- Project Id No. 247) to Dr. A. C. Mondal,"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Prenatal stress (PNS) has gained attention with regard to its impact on hippocampal neurogenesis in neonates which serves as a risk factor for postnatal neurodevelopmental deficits. Evidences from animal models have suggested that depression responsive hypothalamic-pituitary-adrenal (HPA) axis and its hormonal response via cortisol, is responsible for critical neurodevelopmental deficits in the offspring which is transduced due to gestational stress. But knowledge in the area of assessing the effects of maternal chronic unpredictable mild stress (CUMS) on neurogenesis and expression of some key signaling molecules in the offsprings are limited. We have used Wistar rats to induce PNS in offsprings by maternal CUMS during pregnancy. Prefrontal cortex (PFC) and hippocampus were assessed for biomarkers of oxidative stress, neurogenesis, neurodevelopmental signaling molecules and DNA damage in the male Wister offsprings. Our investigations resulted in sufficient evidences which prove how maternal psychological stress has widespread effect on the fetal outcomes via major physiological alteration in the antioxidant levels, neurogenesis, signaling molecules and DNA damage. PNS leads to the upregulation of GSK-3\u03b2 which in turn inhibited mRNA and protein expressions of sonic hedgehog (SHH), \u03b2-catenin, Notch and brain derived neurotrophic factor (BDNF). The study explored multifaceted signaling molecules especially, GSK-3\u03b2 responsible for crosstalks between different neurodevelopmental molecules like SHH, Notch, BDNF and \u03b2-catenin affecting neurodevelopment of the offsprings due to PNS.<\/jats:p>","DOI":"10.1038\/s41598-018-38085-2","type":"journal-article","created":{"date-parts":[[2019,2,4]],"date-time":"2019-02-04T11:04:09Z","timestamp":1549278249000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Effects of chronic unpredictable mild stress induced prenatal stress on neurodevelopment of neonates: Role of GSK-3\u03b2"],"prefix":"10.1038","volume":"9","author":[{"given":"Mahino","family":"Fatima","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurabh","family":"Srivastav","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mir Hilal","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0491-7804","authenticated-orcid":false,"given":"Amal Chandra","family":"Mondal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,2,4]]},"reference":[{"key":"38085_CR1","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1016\/S0193-953X(03)00044-3","volume":"26","author":"DME Sloan","year":"2003","unstructured":"Sloan, D. M. E. & Kornstein, S. G. Gender differences in depression and response to antidepressant treatment. Psychiatric Clinics of North America 26, 581\u2013594 (2003).","journal-title":"Psychiatric Clinics of North America"},{"key":"38085_CR2","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.pop.2008.10.011","volume":"36","author":"SM Marcus","year":"2009","unstructured":"Marcus, S. M. & Heringhausen, J. E. Depression in childbearing women: when depression complicates pregnancy. Primary Care: Clinics in Office Practice 36, 151\u2013165 (2009).","journal-title":"Primary Care: Clinics in Office Practice"},{"key":"38085_CR3","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.brainresrev.2010.06.002","volume":"65","author":"A Charil","year":"2010","unstructured":"Charil, A., Laplante, D. P., Vaillancourt, C. & King, S. Prenatal stress and brain development. Brain research reviews 65, 56\u201379 (2010).","journal-title":"Brain research reviews"},{"key":"38085_CR4","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1097\/01.wnr.0000236849.53682.6d","volume":"17","author":"T Kawamura","year":"2006","unstructured":"Kawamura, T., Chen, J., Takahashi, T., Ichitani, Y. & Nakahara, D. Prenatal stress suppresses cell proliferation in the early developing brain. Neuroreport 17, 1515\u20131518 (2006).","journal-title":"Neuroreport"},{"key":"38085_CR5","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.neulet.2008.09.028","volume":"446","author":"K Odagiri","year":"2008","unstructured":"Odagiri, K. et al. Psychological prenatal stress reduced the number of BrdU immunopositive cells in the dorsal hippocampus without affecting the open field behavior of male and female rats at one month of age. Neuroscience letters 446, 25\u201329 (2008).","journal-title":"Neuroscience letters"},{"key":"38085_CR6","doi-asserted-by":"publisher","first-page":"e24003","DOI":"10.1371\/journal.pone.0024003","volume":"6","author":"I Rayen","year":"2011","unstructured":"Rayen, I. et al. Fluoxetine during development reverses the effects of prenatal stress on depressive-like behavior and hippocampal neurogenesis in adolescence. PloS one 6, e24003 (2011).","journal-title":"PloS one"},{"key":"38085_CR7","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/0149-7634(81)90005-1","volume":"5","author":"RJ Katz","year":"1981","unstructured":"Katz, R. J., Roth, K. A. & Carroll, B. J. Acute and chronic stress effects on open field activity in the rat: implications for a model of depression. Neuroscience & Biobehavioral Reviews 5, 247\u2013251 (1981).","journal-title":"Neuroscience & Biobehavioral Reviews"},{"key":"38085_CR8","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1016\/S0006-3223(99)00253-X","volume":"47","author":"M-C Pardon","year":"2000","unstructured":"Pardon, M.-C., G\u00e9rardin, P., Joubert, C., P\u00e9rez-Diaz, F. & Cohen-Salmon, C. Influence of prepartum chronic ultramild stress on maternal pup care behavior in mice. Biological psychiatry 47, 858\u2013863 (2000).","journal-title":"Biological psychiatry"},{"key":"38085_CR9","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1093\/aje\/kwf176","volume":"157","author":"N Dole","year":"2003","unstructured":"Dole, N. et al. Maternal stress and preterm birth. American journal of epidemiology 157, 14\u201324 (2003).","journal-title":"American journal of epidemiology"},{"key":"38085_CR10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ijdevneu.2017.04.001","volume":"60","author":"M Fatima","year":"2017","unstructured":"Fatima, M., Srivastav, S. & Mondal, A. C. Prenatal stress and depression associated neuronal development in neonates. International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 60, 1\u20137, https:\/\/doi.org\/10.1016\/j.ijdevneu.2017.04.001 (2017).","journal-title":"International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience"},{"key":"38085_CR11","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/S0165-0327(00)00199-3","volume":"64","author":"M Bilici","year":"2001","unstructured":"Bilici, M. et al. Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments. Journal of affective disorders 64, 43\u201351 (2001).","journal-title":"Journal of affective disorders"},{"key":"38085_CR12","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/j.neuint.2009.01.001","volume":"54","author":"G Lucca","year":"2009","unstructured":"Lucca, G. et al. Effects of chronic mild stress on the oxidative parameters in the rat brain. Neurochemistry international 54, 358\u2013362 (2009).","journal-title":"Neurochemistry international"},{"key":"38085_CR13","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.pnpbp.2013.12.012","volume":"50","author":"AE Freitas","year":"2014","unstructured":"Freitas, A. E. et al. Agmatine abolishes restraint stress-induced depressive-like behavior and hippocampal antioxidant imbalance in mice. Progress in Neuro-Psychopharmacology and Biological Psychiatry 50, 143\u2013150 (2014).","journal-title":"Progress in Neuro-Psychopharmacology and Biological Psychiatry"},{"key":"38085_CR14","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1016\/j.pnpbp.2010.05.004","volume":"35","author":"M Maes","year":"2011","unstructured":"Maes, M., Galecki, P., Chang, Y. S. & Berk, M. 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. Progress in Neuro-Psychopharmacology and Biological Psychiatry 35, 676\u2013692 (2011).","journal-title":"Progress in Neuro-Psychopharmacology and Biological Psychiatry"},{"key":"38085_CR15","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.tins.2011.11.004","volume":"35","author":"RS Duman","year":"2012","unstructured":"Duman, R. S. & Voleti, B. Signaling pathways underlying the pathophysiology and treatment of depression: novel mechanisms for rapid-acting agents. Trends in neurosciences 35, 47\u201356 (2012).","journal-title":"Trends in neurosciences"},{"key":"38085_CR16","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/j.ijdevneu.2005.07.005","volume":"23","author":"KL Jaako-Movits","year":"2005","unstructured":"Jaako-Movits, K. L. et al. Developmental lead exposure impairs contextual fear conditioning and reduces adult hippocampal neurogenesis in the rat brain. International Journal of Developmental Neuroscience 23, 627\u2013635 (2005).","journal-title":"International Journal of Developmental Neuroscience"},{"key":"38085_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2165\/11530010-000000000-00000","volume":"24","author":"E Castren","year":"2010","unstructured":"Castren, E. & Rantamuki, T. Role of brain-derived neurotrophic factor in the aetiology of depression. CNS drugs 24, 1\u20137 (2010).","journal-title":"CNS drugs"},{"key":"38085_CR18","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1111\/j.1471-4159.2008.05715.x","volume":"107","author":"JD Lathia","year":"2008","unstructured":"Lathia, J. D., Mattson, M. P. & Cheng, A. Notch: from neural development to neurological disorders. Journal of neurochemistry 107, 1471\u20131481 (2008).","journal-title":"Journal of neurochemistry"},{"key":"38085_CR19","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.tem.2013.10.006","volume":"25","author":"K Marosi","year":"2014","unstructured":"Marosi, K. & Mattson, M. P. BDNF mediates adaptive brain and body responses to energetic challenges. Trends in Endocrinology & Metabolism 25, 89\u201398 (2014).","journal-title":"Trends in Endocrinology & Metabolism"},{"key":"38085_CR20","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/S0925-4773(02)00043-6","volume":"114","author":"G Stump","year":"2002","unstructured":"Stump, G. et al. Notch1 and its ligands Delta-like and Jagged are expressed and active in distinct cell populations in the postnatal mouse brain. Mechanisms of development 114, 153\u2013159 (2002).","journal-title":". Mechanisms of development"},{"key":"38085_CR21","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1001\/archgenpsychiatry.2009.70","volume":"66","author":"B Inkster","year":"2009","unstructured":"Inkster, B. et al. Association of GSK3\u03b2 polymorphisms with brain structural changes in major depressive disorder. Archives of General Psychiatry 66, 721\u2013728 (2009).","journal-title":"Archives of General Psychiatry"},{"key":"38085_CR22","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1111\/j.1601-183X.2010.00617.x","volume":"9","author":"E Saus","year":"2010","unstructured":"Saus, E. et al. A haplotype of glycogen synthase kinase 3\u03b2 is associated with early onset of unipolar major depression. Genes, Brain and Behavior 9, 799\u2013807 (2010).","journal-title":"Genes, Brain and Behavior"},{"key":"38085_CR23","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1093\/embo-reports\/kvf181","volume":"3","author":"BR Henderson","year":"2002","unstructured":"Henderson, B. R. & Fagotto, F. The ins and outs of APC and \u03b2- catenin nuclear transport. EMBO reports 3, 834\u2013839 (2002).","journal-title":"EMBO reports"},{"key":"38085_CR24","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.nbd.2012.05.022","volume":"57","author":"KT Ota","year":"2013","unstructured":"Ota, K. T. & Duman, R. S. Environmental and pharmacological modulations of cellular plasticity: role in the pathophysiology and treatment of depression. Neurobiology of disease 57, 28\u201337 (2013).","journal-title":"Neurobiology of disease"},{"key":"38085_CR25","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1111\/j.1460-9568.2005.04317.x","volume":"22","author":"SB Banerjee","year":"2005","unstructured":"Banerjee, S. B. et al. Recruitment of the Sonic hedgehog signalling cascade in electroconvulsive seizure\u2019 mediated regulation of adult rat hippocampal neurogenesis. European journal of Neuroscience 22, 1570\u20131580 (2005).","journal-title":"European journal of Neuroscience"},{"key":"38085_CR26","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/S0149-7634(03)00014-9","volume":"27","author":"S Maccari","year":"2003","unstructured":"Maccari, S. et al. Prenatal stress and long-term consequences: implications of glucocorticoid hormones. Neuroscience & Biobehavioral Reviews 27, 119\u2013127 (2003).","journal-title":"Neuroscience & Biobehavioral Reviews"},{"key":"38085_CR27","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1016\/j.neubiorev.2005.03.019","volume":"29","author":"FA Henn","year":"2005","unstructured":"Henn, F. A. & Vollmayr, B. Stress models of depression: forming genetically vulnerable strains. Neuroscience & Biobehavioral Reviews 29, 799\u2013804 (2005).","journal-title":"Neuroscience & Biobehavioral Reviews"},{"key":"38085_CR28","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/S1566-2772(03)00086-0","volume":"3","author":"B Vollmayr","year":"2003","unstructured":"Vollmayr, B. & Henn, F. A. Stress models of depression. Clinical Neuroscience Research 3, 245\u2013251 (2003).","journal-title":"Clinical Neuroscience Research"},{"key":"38085_CR29","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/j.ntt.2005.01.015","volume":"27","author":"E Ulupinar","year":"2005","unstructured":"Ulupinar, E. & Yucel, F. Prenatal stress reduces interneuronal connectivity in the rat cerebellar granular layer. Neurotoxicology and teratology 27, 475\u2013484 (2005).","journal-title":"Neurotoxicology and teratology"},{"key":"38085_CR30","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.neuroscience.2005.08.060","volume":"137","author":"DLA Van den Hove","year":"2006","unstructured":"Van den Hove, D. L. A. et al. Prenatal stress and neonatal rat brain development. Neuroscience 137, 145\u2013155 (2006).","journal-title":"Neuroscience"},{"key":"38085_CR31","doi-asserted-by":"publisher","first-page":"297","DOI":"10.4306\/pi.2014.11.3.297","volume":"11","author":"R Banerjee","year":"2014","unstructured":"Banerjee, R., Hazra, S., Ghosh, A. K. & Mondal, A. C. Chronic administration of bacopa monniera increases BDNF protein and mRNA expressions: a study in chronic unpredictable stress induced animal model of depression. Psychiatry Investigation 11, 297\u2013306 (2014).","journal-title":"Psychiatry Investigation"},{"key":"38085_CR32","doi-asserted-by":"publisher","first-page":"74","DOI":"10.4306\/pi.2017.14.1.74","volume":"14","author":"S Hazra","year":"2017","unstructured":"Hazra, S., Kumar, S., Saha, G. K. & Mondal, A. C. Reversion of BDNF, Akt and CREB in Hippocampus of Chronic Unpredictable Stress Induced Rats: Effects of Phytochemical, Bacopa Monnieri. Psychiatry Investigation 14, 74\u201380 (2017).","journal-title":"Psychiatry Investigation"},{"key":"38085_CR33","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1016\/j.leukres.2008.10.026","volume":"33","author":"D Guo","year":"2009","unstructured":"Guo, D. et al. Notch-1 regulates Akt signaling pathway and the expression of cell cycle regulatory proteins cyclin D1, CDK2 and p21 in T-ALL cell lines. Leukemia research 33, 678\u2013685 (2009).","journal-title":"Leukemia research"},{"key":"38085_CR34","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.bbr.2013.12.020","volume":"261","author":"Q-Q Mao","year":"2014","unstructured":"Mao, Q.-Q., Huang, Z., Zhong, X.-M., Xian, Y.-F. & Ip, S.-P. Brain-derived neurotrophic factor signalling mediates the antidepressant-like effect of piperine in chronically stressed mice. Behavioural brain research 261, 140\u2013145 (2014).","journal-title":"Behavioural brain research"},{"key":"38085_CR35","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1007\/s00213-010-2094-2","volume":"214","author":"B Kumar","year":"2011","unstructured":"Kumar, B., Kuhad, A. & Chopra, K. Neuropsychopharmacological effect of sesamol in unpredictable chronic mild stress model of depression: behavioral and biochemical evidences. Psychopharmacology 214, 819\u2013828 (2011).","journal-title":"Psychopharmacology"},{"key":"38085_CR36","doi-asserted-by":"publisher","first-page":"S53","DOI":"10.1016\/S0197-4580(03)00050-2","volume":"24","author":"JK Buitelaar","year":"2003","unstructured":"Buitelaar, J. K., Huizink, A. C., Mulder, E. J., de Medina, P. G. R. & Visser, G. H. Prenatal stress and cognitive development and temperament in infants. Neurobiology of aging 24, S53\u2013S60 (2003).","journal-title":"Neurobiology of aging"},{"key":"38085_CR37","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.neuroscience.2014.12.048","volume":"289","author":"C Borges Filho","year":"2015","unstructured":"Borges Filho, C. et al. Chronic unpredictable mild stress decreases BDNF and NGF levels and NA+, K+-ATPase activity in the hippocampus and prefrontal cortex of mice: antidepressant effect of chrysin. Neuroscience 289, 367\u2013380 (2015).","journal-title":"Neuroscience"},{"key":"38085_CR38","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.neubiorev.2014.05.007","volume":"45","author":"S Moylan","year":"2014","unstructured":"Moylan, S. et al. Oxidative & nitrosative stress in depression: Why so much stress? Neuroscience & Biobehavioral Reviews 45, 46\u201362, https:\/\/doi.org\/10.1016\/j.neubiorev.2014.05.007 (2014).","journal-title":"Neuroscience & Biobehavioral Reviews"},{"key":"38085_CR39","doi-asserted-by":"publisher","first-page":"11032","DOI":"10.1073\/pnas.97.20.11032","volume":"97","author":"V Lemaire","year":"2000","unstructured":"Lemaire, V., Koehl, M., Le Moal, M. & Abrous, D. N. Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocampus. Proceedings of the National Academy of Sciences 97, 11032\u201311037 (2000).","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"38085_CR40","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1016\/S0006-3223(03)00698-X","volume":"54","author":"CL Coe","year":"2003","unstructured":"Coe, C. L. et al. Prenatal stress diminishes neurogenesis in the dentate gyrus of juvenile rhesus monkeys. Biological psychiatry 54, 1025\u20131034 (2003).","journal-title":"Biological psychiatry"},{"key":"38085_CR41","doi-asserted-by":"publisher","unstructured":"Cole, A. GSK3 as a Sensor Determining Cell Fate in theBrain. Frontiers in Molecular Neuroscience 5, https:\/\/doi.org\/10.3389\/fnmol.2012.00004 (2012).","DOI":"10.3389\/fnmol.2012.00004"},{"key":"38085_CR42","doi-asserted-by":"publisher","first-page":"44","DOI":"10.3389\/fendo.2016.00044","volume":"7","author":"J-F Ge","year":"2016","unstructured":"Ge, J.-F., Xu, Y.-Y., Qin, G., Cheng, J.-Q. & Chen, F.-H. Resveratrol ameliorates the anxiety-and depression-like behavior of subclinical hypothyroidism rat: possible involvement of the HPT axis, HPA axis, and Wnt\/\u03b2-catenin pathway. Frontiers in endocrinology 7, 44 (2016).","journal-title":"Frontiers in endocrinology"},{"key":"38085_CR43","doi-asserted-by":"publisher","first-page":"3996","DOI":"10.1242\/dev.129452","volume":"142","author":"J Briscoe","year":"2015","unstructured":"Briscoe, J. & Small, S. Morphogen rules: design principles of gradient-mediated embryo patterning. Development 142, 3996\u20134009 (2015).","journal-title":"Development"},{"key":"38085_CR44","first-page":"75","volume":"97","author":"MP Matise","year":"2011","unstructured":"Matise, M. P. & Wang, H. 4 Sonic Hedgehog Signaling in the Developing CNS: Where It Has Been and Where It Is Going. Current topics in developmentalbiology 97, 75 (2011).","journal-title":"Current topics in developmentalbiology"},{"key":"38085_CR45","doi-asserted-by":"publisher","first-page":"2717","DOI":"10.1242\/dev.015891","volume":"135","author":"M Komada","year":"2008","unstructured":"Komada, M. et al. Hedgehog signaling is involved in development of the neocortex. Development 135, 2717\u20132727 (2008).","journal-title":"Development"},{"key":"38085_CR46","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1177\/1073858414543151","volume":"20","author":"C Metin","year":"2014","unstructured":"Metin, C. & Pedraza, M. Cilia: traffic directors along the road of cortical development. The Neuroscientist 20, 468\u2013482 (2014).","journal-title":"The Neuroscientist"},{"key":"38085_CR47","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1038\/nn2059","volume":"11","author":"Y-G Han","year":"2008","unstructured":"Han, Y.-G. et al. Hedgehog signaling and primary cilia are required for the formation of adult neural stem cells. Nature neuroscience 11, 277\u2013284 (2008).","journal-title":"Nature neuroscience"},{"key":"38085_CR48","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/nn983","volume":"6","author":"K Lai","year":"2003","unstructured":"Lai, K., Kaspar, B. K., Gage, F. H. & Schaffer, D. V. Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo. Nature neuroscience 6, 21\u201327 (2003).","journal-title":"Nature neuroscience"},{"key":"38085_CR49","doi-asserted-by":"publisher","first-page":"4207","DOI":"10.1242\/jcs.105080","volume":"125","author":"N Mitchell","year":"2012","unstructured":"Mitchell, N. et al. Sonic hedgehog regulates presynaptic terminal size, ultrastructure and function in hippocampal neurons. J Cell Sci 125, 4207\u20134213 (2012).","journal-title":"J Cell Sci"},{"key":"38085_CR50","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1038\/35096075","volume":"2","author":"P Cohen","year":"2001","unstructured":"Cohen, P. & Frame, S. The renaissance of GSK3. Nature reviews Molecular cell biology 2, 769\u2013776 (2001).","journal-title":"Nature reviews Molecular cell biology"},{"key":"38085_CR51","doi-asserted-by":"crossref","unstructured":"Kaidanovich-Beilin, O. & Woodgett, J. R. GSK-3: functional insights from cell biology and animal models. Frontiers in Molecular Neuroscience 4 (2011).","DOI":"10.3389\/fnmol.2011.00040"},{"key":"38085_CR52","doi-asserted-by":"publisher","first-page":"1390","DOI":"10.1038\/nn.2408","volume":"12","author":"W-Y Kim","year":"2009","unstructured":"Kim, W.-Y. et al. GSK-3 is a master regulator of neural progenitor homeostasis. Nature neuroscience 12, 1390\u20131397 (2009).","journal-title":"Nature neuroscience"},{"key":"38085_CR53","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.bcp.2013.04.022","volume":"86","author":"F Takahashi-Yanaga","year":"2013","unstructured":"Takahashi-Yanaga, F. Activator or inhibitor? GSK-3 as a new drug target. Biochemical pharmacology 86, 191\u2013199 (2013).","journal-title":"Biochemical pharmacology"},{"key":"38085_CR54","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/emboj\/20.1.27","volume":"20","author":"JJ Lucas","year":"2001","unstructured":"Lucas, J. J. et al. Decreased nuclear \u03b2 catenin, tau hyperphosphorylation and neurodegeneration in GSK -3\u03b2 conditional transgenic mice. The EMBO journal 20, 27\u201339 (2001).","journal-title":"The EMBO journal"},{"key":"38085_CR55","first-page":"82","volume":"85","author":"CM Hedgepeth","year":"1997","unstructured":"Hedgepeth, C. M. et al. Activation of the Wnt signaling pathway: a molecular mechanism for lithium action. Developmentalbiology1 85, 82\u201391 (1997).","journal-title":"Developmentalbiology1"},{"key":"38085_CR56","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1111\/j.1460-9568.2006.05245.x","volume":"25","author":"C Hooper","year":"2007","unstructured":"Hooper, C. et al. Glycogen synthase kinase-3 inhibition is integral to long-term potentiation. European journal of Neuroscience 25, 81\u201386 (2007).","journal-title":"European journal of Neuroscience"},{"key":"38085_CR57","doi-asserted-by":"publisher","first-page":"13502","DOI":"10.1074\/jbc.M110.217604","volume":"286","author":"Y Chen","year":"2011","unstructured":"Chen, Y. et al. Dual Phosphorylation of suppressor of fused (Sufu) by PKA and GSK3\u03b2 regulates its stability and localization in the primary cilium. Journal of Biological Chemistry 286, 13502\u201313511 (2011).","journal-title":"Journal of Biological Chemistry"},{"key":"38085_CR58","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1016\/S0960-9822(02)00888-6","volume":"12","author":"DR Foltz","year":"2002","unstructured":"Foltz, D. R., Santiago, M. C., Berechid, B. E. & Nye, J. S. Glycogen synthase kinase-3\u03b2 modulates notch signaling and stability. Current Biology 12, 1006\u20131011 (2002).","journal-title":"Current Biology"},{"key":"38085_CR59","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.bbamcr.2008.10.002","volume":"1793","author":"YH Jin","year":"2009","unstructured":"Jin, Y. H. et al. Beta-catenin modulates the level and transcriptional activity of Notch1\/NICD through its direct interaction. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research 1793, 290\u2013299 (2009).","journal-title":"Biochimica et Biophysica Acta (BBA)-Molecular Cell Research"},{"key":"38085_CR60","doi-asserted-by":"publisher","first-page":"12620","DOI":"10.1523\/JNEUROSCI.3180-06.2006","volume":"26","author":"GJ Woodhead","year":"2006","unstructured":"Woodhead, G. J., Mutch, C. A., Olson, E. C. & Chenn, A. Cell-autonomous \u03b2-catenin signaling regulates cortical precursor proliferation. Journal of Neuroscience 26, 12620\u201312630 (2006).","journal-title":"Journal of Neuroscience"},{"key":"38085_CR61","doi-asserted-by":"crossref","unstructured":"Hui, J. et al. Modulation of GSK-3\u03b2\/\u03b2-Catenin Signaling Contributes to Learning and Memory Impairment in a Rat Model of Depression. International Journal of Neuropsychopharmacology (2018).","DOI":"10.1093\/ijnp\/pyy040"},{"key":"38085_CR62","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1590\/S0100-879X1999001000009","volume":"32","author":"RJ Cabrera","year":"1999","unstructured":"Cabrera, R. J., Rodriguez-Echandia, E. L., Jatuff, A. S. G. & Foscolo, M. Effects of prenatal exposure to a mild chronic variable stress on body weight, preweaning mortality and rat behavior. Brazilian journal of medical and biological research 32, 1229\u20131237 (1999).","journal-title":"Brazilian journal of medical and biological research"},{"key":"38085_CR63","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1002\/hipo.20825","volume":"21","author":"YAN Biala","year":"2011","unstructured":"Biala, Y. A. N., Bogoch, Y., Bejar, C., Linial, M. & Weinstock, M. Prenatal stress diminishes gender differences in behavior and in expression of hippocampal synaptic genes and proteins in rats. Hippocampus 21, 1114\u20131125 (2011).","journal-title":"Hippocampus"},{"key":"38085_CR64","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1037\/h0077509","volume":"92","author":"RH Chapman","year":"1978","unstructured":"Chapman, R. H. & Stern, J. M. Maternal stress and pituitary-adrenal manipulations during pregnancy in rats: Effects on morphology and sexual behavior of male offspring. Journal of comparative and physiological psychology 92, 1074 (1978).","journal-title":"Journal of comparative and physiological psychology"},{"key":"38085_CR65","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/S1043-2760(02)00690-2","volume":"13","author":"SG Matthews","year":"2002","unstructured":"Matthews, S. G. Early programming of the hypothalamo-pituitary-adrenal axis. Trends in Endocrinology & Metabolism 13, 373\u2013380 (2002).","journal-title":"Trends in Endocrinology & Metabolism"},{"key":"38085_CR66","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1016\/j.psyneuen.2007.07.004","volume":"32","author":"AJ Grippo","year":"2007","unstructured":"Grippo, A. J. et al. Social isolation induces behavioral and neuroendocrine disturbances relevant to depression in female and male prairie voles. Psychoneuroendocrinology 32, 966\u2013980 (2007).","journal-title":"Psychoneuroendocrinology"},{"key":"38085_CR67","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1038\/266730a0","volume":"266","author":"RD Porsolt","year":"1977","unstructured":"Porsolt, R. D., Le Pichon, M. & Jalfre, M. L. Depression: a new animal model sensitive to antidepressant treatments. Nature 266, 730\u2013732 (1977).","journal-title":"Nature"},{"key":"38085_CR68","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.nbd.2014.04.008","volume":"68","author":"Q Zhao","year":"2014","unstructured":"Zhao, Q. et al. Maternal sleep deprivation inhibits hippocampal neurogenesis associated with inflammatory response in young offspring rats. Neurobiology of disease 68, 57\u201365 (2014).","journal-title":"Neurobiology of disease"},{"key":"38085_CR69","unstructured":"Paxinos, G. Watson C1998 The rat brain in stereotaxic coordinates. Academic, San Diego (1998)."},{"key":"38085_CR70","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","volume":"193","author":"OH Lowry","year":"1951","unstructured":"Lowry, O. H., Rosebrough, N. J., Farr, A. L. & Randall, R. J. Protein measurement with the Folin phenol reagent. J biol chem 193, 265\u2013275 (1951).","journal-title":"J biol chem"},{"key":"38085_CR71","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/0003-2697(78)90342-1","volume":"86","author":"M Uchiyama","year":"1978","unstructured":"Uchiyama, M. & Mihara, M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Analytical biochemistry 86, 271\u2013278 (1978).","journal-title":"Analytical biochemistry"},{"key":"38085_CR72","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1159\/000136485","volume":"11","author":"DJ Jollow","year":"1974","unstructured":"Jollow, D. J., Mitchell, J. R., Zampaglione, N. & Gillette, J. R. Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology 11, 151\u2013169 (1974).","journal-title":"Pharmacology"},{"key":"38085_CR73","doi-asserted-by":"crossref","first-page":"3170","DOI":"10.1016\/S0021-9258(19)45228-9","volume":"247","author":"HP Misra","year":"1972","unstructured":"Misra, H. P. & Fridovich, I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. Journal of Biological Chemistry 247, 3170\u20133175 (1972).","journal-title":"Journal of Biological Chemistry"},{"key":"38085_CR74","unstructured":"Clairborne, A. Catalase activity. In Grenwald, R.A. (Ed),Handbook of Methods of Oxigen Radical Research, pp. 283\u2013284, Boca Raton, FL: CRC Press., (1985)."},{"key":"38085_CR75","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1038\/ng1094","volume":"33","author":"VG Cheung","year":"2003","unstructured":"Cheung, V. G. et al. Natural variation in human gene expression assessed in lymphoblastoid cells. Nature genetics 33, 422\u2013425 (2003).","journal-title":"Nature genetics"},{"key":"38085_CR76","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/0014-4827(88)90265-0","volume":"175","author":"NP Singh","year":"1988","unstructured":"Singh, N. P., McCoy, M. T., Tice, R. R. & Schneider, E. L. A simple technique for quantitation of low levels of DNA damage in individual cells. Experimental cell research 175, 184\u2013191 (1988).","journal-title":"Experimental cell research"},{"key":"38085_CR77","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1007\/s00244-014-0024-8","volume":"67","author":"M Fatima","year":"2014","unstructured":"Fatima, M. et al. Assessment of genotoxic induction and deterioration of fish quality in commercial species due to heavy-metal exposure in an urban reservoir. Archives of environmental contamination and toxicology 67, 203\u2013213 (2014).","journal-title":"Archives of environmental contamination and toxicology"},{"key":"38085_CR78","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1289\/ehp.94102s129","volume":"102","author":"SL Anderson","year":"1994","unstructured":"Anderson, S. L. & Wild, G. C. Linking genotoxic responses and reproductive success in ecotoxicology. Environmental Health Perspectives 102, 9 (1994).","journal-title":"Environmental Health Perspectives"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-38085-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-38085-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-38085-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T05:30:32Z","timestamp":1671255032000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-38085-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,4]]},"references-count":78,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["38085"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-38085-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,4]]},"assertion":[{"value":"20 February 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 December 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 February 2019","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":"1305"}}