{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T05:48:29Z","timestamp":1774072109583,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondos Federales","award":["HIM\/2018-046"],"award-info":[{"award-number":["HIM\/2018-046"]}]},{"name":"Fondos Federales","award":["HIM\/2016-037"],"award-info":[{"award-number":["HIM\/2016-037"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Learning alterations in the child population may be linked to gestational diabetes as a causal factor, though this remains an open and highly controversial question. In that sense, it has been reported that maternal hyperglycemia generates a threatening condition that affects hippocampal development in offspring. The pyramidal cells of the CA3 subfield, a key structure in learning and memory processes, are particularly important in cognitive deficiencies. We evaluate the effect of the hyperglycemic intrauterine environment on hippocampal histomorphometry in offspring, correlating it with spatial learning and memory, as well as the morphology of dendrites and spines in 30-day-old pups (P30). The maternal hyperglycemia affected the body weight, height, and brain size of fetuses at 21 days of gestation (F21), newborn pups (P0) and P30 pups from diabetic rats, which were smaller compared to the control group. Consequently, this resulted in a decrease in hippocampal size, lower neuronal density and cytoarchitectural disorganization in the CA3 region of the hippocampus in the offspring at the three ages studied. The behavioral tests performed showed a direct relationship between morpho-histological alterations and deficiencies in learning and memory, as well as alterations in the morphology of the dendrites and spines. Therefore, knowing the harmful effects caused by gestational diabetes can be of great help to establish therapeutic and educational strategies that can help to improve learning and memory in children.<\/jats:p>","DOI":"10.3390\/ijms252111335","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T04:10:14Z","timestamp":1729570214000},"page":"11335","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Harmful Effects on the Hippocampal Morpho-Histology and on Learning and Memory in the Offspring of Rats with Streptozotocin-Induced Diabetes"],"prefix":"10.3390","volume":"25","author":[{"given":"Marcela","family":"Salazar-Garc\u00eda","sequence":"first","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en Biolog\u00eda del Desarrollo y Teratog\u00e9nesis Experimental, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Mexico City 06720, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Villavicencio-Guzm\u00e1n","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en Biolog\u00eda del Desarrollo y Teratog\u00e9nesis Experimental, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Mexico City 06720, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Revilla-Monsalve","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n en Enfermedades Metab\u00f3licas, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06725, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1995-0308","authenticated-orcid":false,"given":"Carlos C\u00e9sar","family":"Pati\u00f1o-Morales","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en Biolog\u00eda del Desarrollo y Teratog\u00e9nesis Experimental, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Mexico City 06720, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0403-537X","authenticated-orcid":false,"given":"Ricardo","family":"Jaime-Cruz","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias de la Salud, Universidad Tecnol\u00f3gica de M\u00e9xico-UNITEC M\u00e9xico-Campus Sur, Mexico City 09810, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4317-0942","authenticated-orcid":false,"given":"Tania Cristina","family":"Ram\u00edrez-Fuentes","sequence":"additional","affiliation":[{"name":"Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Escuela Superior de Medicina del Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4907-437X","authenticated-orcid":false,"given":"Juan Carlos","family":"Corona","sequence":"additional","affiliation":[{"name":"Laboratory of Neurosciences, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Mexico City 06720, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rodolaki, K., Pergialiotis, V., Iakovidou, N., Boutsikou, T., Iliodromiti, Z., and Kanaka-Gantenbein, C. (2023). The impact of maternal diabetes on the future health and neurodevelopment of the offspring: A review of the evidence. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1125628"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1093\/ije\/dyaa212","article-title":"Association of maternal diabetes with neurodevelopmental disorders: Autism spectrum disorders, attention-deficit\/hyperactivity disorder and intellectual disability","volume":"50","author":"Chen","year":"2021","journal-title":"Int. J. Epidemiol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Rowland, J., and Wilson, C.A. (2021). The association between gestational diabetes and ASD and ADHD: A systematic review and meta-analysis. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-84573-3"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"John, C.M., Mohamed Yusof, N.I.S., Abdul Aziz, S.H., and Mohd Fauzi, F. (2018). Maternal Cognitive Impairment Associated with Gestational Diabetes Mellitus-A Review of Potential Contributing Mechanisms. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123894"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1001\/archpediatrics.2011.784","article-title":"Exposure to gestational diabetes mellitus and low socioeconomic status: Effects on neurocognitive development and risk of attention-deficit\/hyperactivity disorder in offspring","volume":"166","author":"Nomura","year":"2012","journal-title":"Arch. Pediatr. Adolesc. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"963735","DOI":"10.1155\/2012\/963735","article-title":"Associations of existing diabetes, gestational diabetes, and glycosuria with offspring IQ and educational attainment: The Avon Longitudinal Study of Parents and Children","volume":"2012","author":"Fraser","year":"2012","journal-title":"Exp. Diabetes Res."},{"key":"ref_7","first-page":"231","article-title":"Hyperglycaemia in pregnancy: Effects on the offspring behaviour with special reference to anxiety paradigms","volume":"38","author":"Ramanathan","year":"2000","journal-title":"Indian J. Exp. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1177\/153537020322800204","article-title":"Maternal hyperglycemia leads to gender-dependent deficits in learning and memory in offspring","volume":"228","author":"Kinney","year":"2003","journal-title":"Exp. Biol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.neuroscience.2016.01.025","article-title":"The impacts of diabetes in pregnancy on hippocampal synaptogenesis in rat neonates","volume":"318","author":"Hami","year":"2016","journal-title":"Neuroscience"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"239","DOI":"10.4103\/0972-2327.104323","article-title":"Hippocampus in health and disease: An overview","volume":"15","author":"Anand","year":"2012","journal-title":"Ann. Indian Acad. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"412","DOI":"10.4239\/wjd.v6.i3.412","article-title":"Some of the experimental and clinical aspects of the effects of the maternal diabetes on developing hippocampus","volume":"6","author":"Hami","year":"2015","journal-title":"World J. Diabetes"},{"key":"ref_12","first-page":"354265","article-title":"Importance of maternal diabetes on the chronological deregulation of the intrauterine development: An experimental study in rat","volume":"2015","year":"2015","journal-title":"J. Diabetes Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Salazar-Garcia, M., and Corona, J.C. (2021). The Use of Natural Compounds as a Strategy to Counteract Oxidative Stress in Animal Models of Diabetes Mellitus. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22137009"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1210\/er.2009-0038","article-title":"Animal models in diabetes and pregnancy","volume":"31","author":"Jawerbaum","year":"2010","journal-title":"Endocr. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1758-5996-1-21","article-title":"Animal models for clinical and gestational diabetes: Maternal and fetal outcomes","volume":"1","author":"Kiss","year":"2009","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1037\/a0040455","article-title":"Neurocognitive consequences of diabetes","volume":"71","author":"Ryan","year":"2016","journal-title":"Am. Psychol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s11892-016-0775-x","article-title":"Diabetes and Cognitive Impairment","volume":"16","author":"Zilliox","year":"2016","journal-title":"Curr. Diabetes Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.3923\/jbs.2008.1027.1032","article-title":"Effect of Maternal Diabetes on Hippocampus Neuronal Density in Neonatal Rats","volume":"8","author":"Tehranipour","year":"2008","journal-title":"J. Biol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.jnutbio.2014.04.012","article-title":"Hippocampal apoptosis involved in learning deficits in the offspring exposed to maternal high sucrose diets","volume":"25","author":"Kuang","year":"2014","journal-title":"J. Nutr. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ijdevneu.2016.04.009","article-title":"Diabetes during pregnancy enhanced neuronal death in the hippocampus of rat offspring","volume":"51","author":"Lotfi","year":"2016","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wu, J., Fang, Y., Tan, X., Kang, S., Yue, X., Rao, Y., Huang, H., Liu, M., Qiu, S., and Yap, P.T. (2023). Detecting type 2 diabetes mellitus cognitive impairment using whole-brain functional connectivity. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-28163-5"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s10571-019-00658-8","article-title":"Severe Uncontrolled Maternal Hyperglycemia Induces Microsomia and Neurodevelopment Delay Accompanied by Apoptosis, Cellular Survival, and Neuroinflammatory Deregulation in Rat Offspring Hippocampus","volume":"39","author":"Piazza","year":"2019","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Huerta-Cervantes, M., Pena-Montes, D.J., Montoya-Perez, R., Trujillo, X., Huerta, M., Lopez-Vazquez, M.A., Olvera-Cortes, M.E., and Saavedra-Molina, A. (2020). Gestational Diabetes Triggers Oxidative Stress in Hippocampus and Cerebral Cortex and Cognitive Behavior Modifications in Rat Offspring: Age- and Sex-Dependent Effects. Nutrients, 12.","DOI":"10.3390\/nu12020376"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1002\/bdra.23057","article-title":"Association between weight gain during pregnancy and neural tube defects and gastroschisis in offspring","volume":"94","author":"Yang","year":"2012","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"key":"ref_25","unstructured":"Misirliyan, S.S., Boehning, A.P., and Shah, M. (2023). Development Milestones. StatPearls, StatPearls Publishing."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1038\/nn.4661","article-title":"Viewpoints: How the hippocampus contributes to memory, navigation and cognition","volume":"20","author":"Lisman","year":"2017","journal-title":"Nat. Neurosci."},{"key":"ref_27","first-page":"71","article-title":"Gestational diabetes induced neuronal loss in CA1 and CA3 subfields of rat hippocampus in early postnatal life","volume":"71","author":"Golalipour","year":"2012","journal-title":"Folia Morphol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"101669","DOI":"10.1016\/j.jchemneu.2019.101669","article-title":"Volumetric investigation of the hippocampus in rat offspring due to diabetes in pregnancy-A stereological study","volume":"101","author":"Sadeghi","year":"2019","journal-title":"J. Chem. Neuroanat."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.neuroscience.2015.06.063","article-title":"Chronic maternal hyperglycemia induced during mid-pregnancy in rats increases RAGE expression, augments hippocampal excitability, and alters behavior of the offspring","volume":"303","author":"Chandna","year":"2015","journal-title":"Neuroscience"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s12974-017-0859-9","article-title":"Exposure to gestational diabetes mellitus induces neuroinflammation, derangement of hippocampal neurons, and cognitive changes in rat offspring","volume":"14","author":"Vuong","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/s41398-020-01096-7","article-title":"Gestational diabetes induces behavioral and brain gene transcription dysregulation in adult offspring","volume":"10","author":"Hamshawi","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Valle-Bautista, R., Marquez-Valadez, B., Fragoso-Cabrera, A.D., Garcia-Lopez, G., Diaz, N.F., Herrera-Lopez, G., Griego, E., Galvan, E.J., Arias-Montano, J.A., and Molina-Hernandez, A. (2020). Impaired Cortical Cytoarchitecture and Reduced Excitability of Deep-Layer Neurons in the Offspring of Diabetic Rats. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.564561"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.brainres.2005.04.048","article-title":"Alteration in dendritic morphology of cortical neurons in rats with diabetes mellitus induced by streptozotocin","volume":"1048","author":"Flores","year":"2005","journal-title":"Brain Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1111\/j.1399-5448.2008.00431.x","article-title":"Hyperglycemia not hypoglycemia alters neuronal dendrites and impairs spatial memory","volume":"9","author":"Malone","year":"2008","journal-title":"Pediatr. Diabetes"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Luo, S.S., Zou, K.X., Zhu, H., Cheng, Y., Yan, Y.S., Sheng, J.Z., Huang, H.F., and Ding, G.L. (2022). Integrated Multi-Omics Analysis Reveals the Effect of Maternal Gestational Diabetes on Fetal Mouse Hippocampi. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.748862"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2583","DOI":"10.1002\/hbm.25390","article-title":"Selective morphological and volumetric alterations in the hippocampus of children exposed in utero to gestational diabetes mellitus","volume":"42","author":"Lynch","year":"2021","journal-title":"Hum. Brain Mapp."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Camuso, S., La Rosa, P., Fiorenza, M.T., and Canterini, S. (2022). Pleiotropic effects of BDNF on the cerebellum and hippocampus: Implications for neurodevelopmental disorders. Neurobiol. Dis., 163.","DOI":"10.1016\/j.nbd.2021.105606"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"101946","DOI":"10.1016\/j.jchemneu.2021.101946","article-title":"Maternal diabetes-induced alterations in the expression of brain-derived neurotrophic factor in the developing rat hippocampus","volume":"114","author":"Sardar","year":"2021","journal-title":"J. Chem. Neuroanat."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Wu, K.L.H., Liu, W.C., Wu, C.W., Fu, M.H., Huang, H.M., Tain, Y.L., Liang, C.K., Hung, C.Y., Chen, I.C., and Hung, P.L. (2024). Butyrate reduction and HDAC4 increase underlie maternal high fructose-induced metabolic dysfunction in hippocampal astrocytes in female rats. J. Nutr. Biochem., 126.","DOI":"10.1016\/j.jnutbio.2024.109571"},{"key":"ref_40","unstructured":"(2001). Norma Oficial Mexicana, Especificaciones Tecnicas para la Produccion, Cuidado y Uso de los Animales de Laboratorio (Standard No. NOM-062-200-1999)."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7754","DOI":"10.1007\/s12035-019-1624-0","article-title":"Late Cognitive Consequences of Gestational Diabetes to the Offspring, in a New Mouse Model","volume":"56","author":"Figueiredo","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"39","DOI":"10.31083\/j.jin2302039","article-title":"No Effects of Decanoic Acid on Locomotor Activity and Antioxidant Defences in an Experimental Animal Model of Attention-Deficit\/Hyperactivity Disorder","volume":"23","author":"Corona","year":"2024","journal-title":"J. Integr. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1038\/nprot.2006.116","article-title":"Morris water maze: Procedures for assessing spatial and related forms of learning and memory","volume":"1","author":"Vorhees","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1002\/1098-1063(2000)10:5<501::AID-HIPO1>3.0.CO;2-T","article-title":"Overview on the structure, composition, function, development, and plasticity of hippocampal dendritic spines","volume":"10","author":"Sorra","year":"2000","journal-title":"Hippocampus"},{"key":"ref_45","first-page":"387","article-title":"Dendritic organization in the neurons of the visual and motor cortices of the cat","volume":"87","author":"Sholl","year":"1953","journal-title":"J. Anat."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1002\/syn.20837","article-title":"Dendritic morphology of neurons in medial prefrontal cortex, hippocampus, and nucleus accumbens in adult SH rats","volume":"65","author":"Sanchez","year":"2011","journal-title":"Synapse"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/21\/11335\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:17:48Z","timestamp":1760113068000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/21\/11335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,22]]},"references-count":46,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["ijms252111335"],"URL":"https:\/\/doi.org\/10.3390\/ijms252111335","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,22]]}}}