{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T05:04:44Z","timestamp":1782968684971,"version":"3.54.5"},"reference-count":90,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,7]],"date-time":"2023-01-07T00:00:00Z","timestamp":1673049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MIUR \u201cProgetto Eccellenza\u201d","award":["ARS01_01226"],"award-info":[{"award-number":["ARS01_01226"]}]},{"name":"MIUR \u201cProgetto Eccellenza\u201d","award":["2017ZFJCS3"],"award-info":[{"award-number":["2017ZFJCS3"]}]},{"DOI":"10.13039\/501100003407","name":"PON \u201cRicerca e Innovazione\u201d","doi-asserted-by":"publisher","award":["ARS01_01226"],"award-info":[{"award-number":["ARS01_01226"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"PON \u201cRicerca e Innovazione\u201d","doi-asserted-by":"publisher","award":["2017ZFJCS3"],"award-info":[{"award-number":["2017ZFJCS3"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"name":"PRIN","award":["ARS01_01226"],"award-info":[{"award-number":["ARS01_01226"]}]},{"name":"PRIN","award":["2017ZFJCS3"],"award-info":[{"award-number":["2017ZFJCS3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Patients affected by diabetes mellitus (DM) show diabetic encephalopathy with an increased risk of cognitive deficits, dementia and Alzheimer\u2019s disease, but the mechanisms are not fully explored. In the male animal models of DM, the development of cognitive impairment seems to be the result of the concomitance of different processes such as neuroinflammation, oxidative stress, mitochondrial dysfunction, and aberrant synaptogenesis. However, even if diabetic encephalopathy shows some sex-dimorphic features, no observations in female rats have been so far reported on these aspects. Therefore, in an experimental model of type 1 DM (T1DM), we explored the impact of one month of pathology on memory abilities by the novel object recognition test and on neuroinflammation, synaptogenesis and mitochondrial functionality. Moreover, given that steroids are involved in memory and learning, we also analysed their levels and receptors. We reported that memory dysfunction can be associated with different features in the female hippocampus and cerebral cortex. Indeed, in the hippocampus, we observed aberrant synaptogenesis and neuroinflammation but not mitochondrial dysfunction and oxidative stress, possibly due to the results of locally increased levels of progesterone metabolites (i.e., dihydroprogesterone and allopregnanolone). These observations suggest specific brain-area effects of T1DM since different alterations are observed in the cerebral cortex.<\/jats:p>","DOI":"10.3390\/ijms24021196","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T02:09:39Z","timestamp":1673230179000},"page":"1196","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Diabetic Encephalopathy in a Preclinical Experimental Model of Type 1 Diabetes Mellitus: Observations in Adult Female Rat"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4112-8361","authenticated-orcid":false,"given":"Eva","family":"Falvo","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze Farmacologiche e Biomolecolari, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7741-826X","authenticated-orcid":false,"given":"Silvia","family":"Giatti","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmacologiche e Biomolecolari, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1454-2196","authenticated-orcid":false,"given":"Silvia","family":"Diviccaro","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmacologiche e Biomolecolari, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5935-3597","authenticated-orcid":false,"given":"Lucia","family":"Cioffi","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmacologiche e Biomolecolari, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7247-0322","authenticated-orcid":false,"given":"Monika","family":"Herian","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmacologiche e Biomolecolari, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Brivio","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmacologiche e Biomolecolari, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7946-2424","authenticated-orcid":false,"given":"Francesca","family":"Calabrese","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmacologiche e Biomolecolari, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2115-778X","authenticated-orcid":false,"given":"Donatella","family":"Caruso","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmacologiche e Biomolecolari, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0861-8967","authenticated-orcid":false,"given":"Roberto Cosimo","family":"Melcangi","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmacologiche e Biomolecolari, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.2337\/db14-0348","article-title":"Brain changes underlying cognitive dysfunction in diabetes: What can we learn from MRI?","volume":"63","author":"Biessels","year":"2014","journal-title":"Diabetes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/S0166-2236(00)01656-8","article-title":"Cognition and synaptic plasticity in diabetes mellitus","volume":"23","author":"Gispen","year":"2000","journal-title":"Trends Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1007\/s00702-017-1763-2","article-title":"The diabetic brain and cognition","volume":"124","author":"Riederer","year":"2017","journal-title":"J. Neural. Transm."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.physbeh.2016.05.041","article-title":"Alzheimer\u2019s disease: Is this a brain specific diabetic condition?","volume":"164","author":"Rani","year":"2016","journal-title":"Physiol. Behav."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.neubiorev.2016.03.005","article-title":"Diabetes and Alzheimer\u2019s disease crosstalk","volume":"64","author":"Shi","year":"2016","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1080\/13803390490514875","article-title":"The relationship between impaired glucose tolerance, type 2 diabetes, and cognitive function","volume":"26","author":"Awad","year":"2004","journal-title":"J. Clin. Exp. Neuropsychol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.neurobiolaging.2005.08.017","article-title":"High-fat diets, insulin resistance and declining cognitive function","volume":"26","author":"Greenwood","year":"2005","journal-title":"Neurobiol. Aging"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.neurobiolaging.2005.09.014","article-title":"Impact of impaired glucose tolerance and type 2 diabetes on cognitive aging","volume":"26","author":"Messier","year":"2005","journal-title":"Neurobiol. Aging"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.neurobiolaging.2005.09.003","article-title":"Studies of the effects of high fat diets on cognitive function in a rat model","volume":"26","author":"Winocur","year":"2005","journal-title":"Neurobiol. Aging"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1007\/s00125-015-3515-x","article-title":"Risk of dementia in patients hospitalised with type 1 and type 2 diabetes in England, 1998-2011: A retrospective national record linkage cohort study","volume":"58","author":"Smolina","year":"2015","journal-title":"Diabetologia"},{"key":"ref_11","first-page":"329632","article-title":"Structural and ultrastructural analysis of cerebral cortex, cerebellum, and hypothalamus from diabetic rats","volume":"2009","author":"Rincon","year":"2009","journal-title":"Exp. Diabetes Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"937","DOI":"10.3233\/JAD-121762","article-title":"Axonal and dendritic changes are associated with diabetic encephalopathy in rats: An important risk factor for Alzheimer\u2019s disease","volume":"34","author":"Zhou","year":"2013","journal-title":"J. Alzheimers Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s12031-010-9344-y","article-title":"Dihydroprogesterone increases the gene expression of myelin basic protein in spinal cord of diabetic rats","volume":"42","author":"Pesaresi","year":"2010","journal-title":"J. Mol. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1007\/s11064-006-9260-2","article-title":"Alterations in mRNA expression of myelin proteins in the sciatic nerves and brains of streptozotocin-induced diabetic rats","volume":"32","author":"Kawashima","year":"2007","journal-title":"Neurochem. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.jsbmb.2017.02.002","article-title":"Diabetes alters myelin lipid profile in rat cerebral cortex: Protective effects of dihydroprogesterone","volume":"168","author":"Cermenati","year":"2017","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Baptista, F.I., Pinto, M.J., Elvas, F., Almeida, R.D., and Ambrosio, A.F. (2013). Diabetes alters KIF1A and KIF5B motor proteins in the hippocampus. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065515"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0006-8993(98)00510-1","article-title":"Water maze learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats: Effects of insulin treatment","volume":"800","author":"Biessels","year":"1998","journal-title":"Brain Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.2337\/diab.45.9.1259","article-title":"Place learning and hippocampal synaptic plasticity in streptozotocin-induced diabetic rats","volume":"45","author":"Biessels","year":"1996","journal-title":"Diabetes"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.brainres.2005.12.070","article-title":"Synaptic transmission changes in the pyramidal cells of the hippocampus in streptozotocin-induced diabetes mellitus in rats","volume":"1073\u20131074","author":"Kamal","year":"2006","journal-title":"Brain Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.biopha.2018.02.115","article-title":"Centella asiatica ameliorates diabetes-induced stress in rat tissues via influences on antioxidants and inflammatory cytokines","volume":"101","author":"Masola","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.prostaglandins.2018.05.004","article-title":"An inhibitor of soluble epoxide hydrolase ameliorates diabetes-induced learning and memory impairment in rats","volume":"136","author":"Minaz","year":"2018","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.3233\/JAD-150820","article-title":"Region-Specific Vulnerability to Oxidative Stress, Neuroinflammation, and Tau Hyperphosphorylation in Experimental Diabetes Mellitus Mice","volume":"51","author":"Elahi","year":"2016","journal-title":"J. Alzheimers Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.freeradbiomed.2020.09.017","article-title":"Hyperglycemia in a type 1 Diabetes Mellitus model causes a shift in mitochondria coupled-glucose phosphorylation and redox metabolism in rat brain","volume":"160","author":"Machado","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.bbadis.2010.07.001","article-title":"Cortical and hippocampal mitochondria bioenergetics and oxidative status during hyperglycemia and\/or insulin-induced hypoglycemia","volume":"1802","author":"Cardoso","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nbd.2012.08.008","article-title":"Insulin-induced recurrent hypoglycemia exacerbates diabetic brain mitochondrial dysfunction and oxidative imbalance","volume":"49","author":"Cardoso","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jneuroim.2017.11.006","article-title":"Pinocembrin alleviates cognition deficits by inhibiting inflammation in diabetic mice","volume":"314","author":"Pei","year":"2018","journal-title":"J. Neuroimmunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3848","DOI":"10.1007\/s12035-021-02390-1","article-title":"The mTOR\/NF-kappaB Pathway Mediates Neuroinflammation and Synaptic Plasticity in Diabetic Encephalopathy","volume":"58","author":"Xu","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.phymed.2016.04.008","article-title":"Reversal of diabetes-induced behavioral and neurochemical deficits by cinnamaldehyde","volume":"23","author":"Jawale","year":"2016","journal-title":"Phytomedicine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.neuro.2016.09.009","article-title":"Protective effect of betulin on cognitive decline in streptozotocin (STZ)-induced diabetic rats","volume":"57","author":"Ma","year":"2016","journal-title":"Neurotoxicology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.neuropharm.2015.12.007","article-title":"Salidroside ameliorates arthritis-induced brain cognition deficits by regulating Rho\/ROCK\/NF-kappaB pathway","volume":"103","author":"Zhu","year":"2016","journal-title":"Neuropharmacology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ejphar.2016.11.033","article-title":"S-allyl cysteine ameliorates cognitive deficits in streptozotocin-diabetic rats via suppression of oxidative stress, inflammation, and acetylcholinesterase","volume":"794","author":"Baluchnejadmojarad","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.pbb.2008.12.012","article-title":"Suppression of NF-kappabeta signaling pathway by tocotrienol can prevent diabetes associated cognitive deficits","volume":"92","author":"Kuhad","year":"2009","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1021\/acschemneuro.5b00240","article-title":"Inside the Diabetic Brain: Role of Different Players Involved in Cognitive Decline","volume":"7","author":"Gaspar","year":"2016","journal-title":"ACS Chem. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1007\/s00018-007-7403-5","article-title":"Neuroactive steroids: State of the art and new perspectives","volume":"65","author":"Melcangi","year":"2008","journal-title":"Cell Mol. Life Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.neubiorev.2015.09.023","article-title":"Levels and actions of neuroactive steroids in the nervous system under physiological and pathological conditions: Sex-specific features","volume":"67","author":"Melcangi","year":"2016","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e12996","DOI":"10.1111\/jne.12996","article-title":"Allopregnanolone: An overview on its synthesis and effects","volume":"34","author":"Diviccaro","year":"2021","journal-title":"J. Neuroendocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"R125","DOI":"10.1530\/JME-12-0127","article-title":"Neuroactive steroids, their metabolites and neuroinflammation","volume":"49","author":"Giatti","year":"2012","journal-title":"J. Mol. Endocrinol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pneurobio.2018.06.007","article-title":"Neuroactive steroids, neurosteroidogenesis and sex","volume":"176","author":"Giatti","year":"2019","journal-title":"Prog. Neurobiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.pneurobio.2013.07.006","article-title":"Levels and actions of progesterone and its metabolites in the nervous system during physiological and pathological conditions","volume":"113","author":"Melcangi","year":"2014","journal-title":"Prog. Neurobiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1007\/s11886-014-0467-6","article-title":"Endogenous sex hormones, metabolic syndrome, and diabetes in men and women","volume":"16","author":"Kim","year":"2014","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1093\/humupd\/dms024","article-title":"Female reproduction and type 1 diabetes: From mechanisms to clinical findings","volume":"18","author":"Codner","year":"2012","journal-title":"Hum. Reprod Update"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1007\/s00441-012-1387-7","article-title":"The effects of type 1 diabetes on the hypothalamic, pituitary and testes axis","volume":"349","author":"Schoeller","year":"2012","journal-title":"Cell Tissue Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.neuint.2007.06.004","article-title":"Evaluation of neuroactive steroid levels by liquid chromatography-tandem mass spectrometry in central and peripheral nervous system: Effect of diabetes","volume":"52","author":"Caruso","year":"2008","journal-title":"Neurochem. Int."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.yhbeh.2009.04.008","article-title":"Sex differences in neuroactive steroid levels in the nervous system of diabetic and non-diabetic rats","volume":"57","author":"Pesaresi","year":"2010","journal-title":"Horm. Behav."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.yfrne.2017.07.006","article-title":"Neuroactive steroids and diabetic complications in the nervous system","volume":"48","author":"Giatti","year":"2018","journal-title":"Front. Neuroendocrinol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.jsbmb.2016.11.019","article-title":"Short-term effects of diabetes on neurosteroidogenesis in the rat hippocampus","volume":"167","author":"Romano","year":"2017","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1007\/s125-002-8250-6","article-title":"Impaired intellectual development in children with Type I diabetes: Association with HbA(1c), age at diagnosis and sex","volume":"45","author":"Schoenle","year":"2002","journal-title":"Diabetologia"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/S0074-7742(02)51013-8","article-title":"Diabetes, the brain, and behavior: Is there a biological mechanism underlying the association between diabetes and depression?","volume":"51","author":"Jacobson","year":"2002","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0014-2999(02)01486-3","article-title":"Ageing and diabetes: Implications for brain function","volume":"441","author":"Biessels","year":"2002","journal-title":"Eur. J. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1210\/er.2007-0034","article-title":"Cognitive dysfunction and diabetes mellitus","volume":"29","author":"Kodl","year":"2008","journal-title":"Endocr. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/S1474-4422(08)70021-8","article-title":"Cognition and diabetes: A lifespan perspective","volume":"7","author":"Biessels","year":"2008","journal-title":"Lancet Neurol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1212\/WNL.53.9.1992","article-title":"Gender differences in the incidence of AD and vascular dementia: The EURODEM Studies. EURODEM Incidence Research Group","volume":"53","author":"Andersen","year":"1999","journal-title":"Neurology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1212\/WNL.48.1.132","article-title":"Very old women at highest risk of dementia and Alzheimer\u2019s disease: Incidence data from the Kungsholmen Project, Stockholm","volume":"48","author":"Fratiglioni","year":"1997","journal-title":"Neurology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"539","DOI":"10.3171\/jns.2000.93.4.0539","article-title":"Do women fare worse: A metaanalysis of gender differences in traumatic brain injury outcome","volume":"93","author":"Farace","year":"2000","journal-title":"J. Neurosurg."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1080\/09602010600814729","article-title":"Gender differences in executive functions following traumatic brain injury","volume":"17","author":"Niemeier","year":"2007","journal-title":"Neuropsychol. Rehabil."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.comppsych.2007.06.012","article-title":"Sex differences in depression symptoms in treatment-seeking adults: Confirmatory analyses from the Sequenced Treatment Alternatives to Relieve Depression study","volume":"49","author":"Marcus","year":"2008","journal-title":"Compr. Psychiatry"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0165-0327(02)00113-1","article-title":"Are gender differences in depression explained by gender differences in co-morbid anxiety?","volume":"77","author":"Simonds","year":"2003","journal-title":"J. Affect. Disord"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.physbeh.2007.11.037","article-title":"Neurobiology of anorexia and bulimia nervosa","volume":"94","author":"Kaye","year":"2008","journal-title":"Physiol. Behav."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.jdiacomp.2014.12.008","article-title":"Gender difference in diabetes-associated risk of first-ever and recurrent ischemic stroke","volume":"29","author":"Policardo","year":"2015","journal-title":"J. Diabetes Complicat."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"104855","DOI":"10.1016\/j.neubiorev.2022.104855","article-title":"Neuronal circuitry for recognition memory of object and place in rodent models","volume":"141","author":"Chao","year":"2022","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1016\/j.psyneuen.2013.04.016","article-title":"Comparison of plasma and cerebrospinal fluid levels of neuroactive steroids with their brain, spinal cord and peripheral nerve levels in male and female rats","volume":"38","author":"Caruso","year":"2013","journal-title":"Psychoneuroendocrinology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.neuroscience.2003.09.023","article-title":"Allopregnanolone and progesterone decrease cell death and cognitive deficits after a contusion of the rat pre-frontal cortex","volume":"123","author":"Djebaili","year":"2004","journal-title":"Neuroscience"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.annemergmed.2005.12.011","article-title":"Allopregnanolone, a progesterone metabolite, is more effective than progesterone in reducing cortical infarct volume after transient middle cerebral artery occlusion","volume":"47","author":"Sayeed","year":"2006","journal-title":"Ann. Emerg. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.brainres.2009.01.045","article-title":"Direct inhibition of the mitochondrial permeability transition pore: A possible mechanism for better neuroprotective effects of allopregnanolone over progesterone","volume":"1263","author":"Sayeed","year":"2009","journal-title":"Brain Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1002\/neu.20293","article-title":"Reduced metabolites mediate neuroprotective effects of progesterone in the adult rat hippocampus. The synthetic progestin medroxyprogesterone acetate (Provera) is not neuroprotective","volume":"66","author":"Ciriza","year":"2006","journal-title":"J. Neurobiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"100836","DOI":"10.1016\/j.yfrne.2020.100836","article-title":"Physiopathological role of the enzymatic complex 5alpha-reductase and 3alpha\/beta-hydroxysteroid oxidoreductase in the generation of progesterone and testosterone neuroactive metabolites","volume":"57","author":"Giatti","year":"2020","journal-title":"Front. Neuroendocrinol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/nrn1703","article-title":"Neurosteroids: Endogenous regulators of the GABA(A) receptor","volume":"6","author":"Belelli","year":"2005","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.pharmthera.2007.03.011","article-title":"Neurosteroid binding sites on GABA(A) receptors","volume":"116","author":"Hosie","year":"2007","journal-title":"Pharmacol. Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.jsbmb.2014.09.001","article-title":"Progesterone and allopregnanolone in the central nervous system: Response to injury and implication for neuroprotection","volume":"146","author":"Guennoun","year":"2015","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.pneurobio.2013.09.004","article-title":"Revisiting the roles of progesterone and allopregnanolone in the nervous system: Resurgence of the progesterone receptors","volume":"113","author":"Schumacher","year":"2014","journal-title":"Prog. Neurobiol."},{"key":"ref_71","first-page":"1262","article-title":"Allopregnanolone synthesis in cerebellar granule cells: Roles in regulation of GABA(A) receptor expression and function during progesterone treatment and withdrawal","volume":"57","author":"Follesa","year":"2000","journal-title":"Mol. Pharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.pbb.2006.07.002","article-title":"Plastic neuronal changes in GABA(A) receptor gene expression induced by progesterone metabolites: In vitro molecular and functional studies","volume":"84","author":"Biggio","year":"2006","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"9695412","DOI":"10.1155\/2019\/9695412","article-title":"Mitochondria- and Oxidative Stress-Targeting Substances in Cognitive Decline-Related Disorders: From Molecular Mechanisms to Clinical Evidence","volume":"2019","author":"Lejri","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1007\/s11064-018-2561-4","article-title":"Increased Superoxide Dismutase 2 by Allopregnanolone Ameliorates ROS-Mediated Neuronal Death in Mice with Pilocarpine-Induced Status Epilepticus","volume":"43","author":"Cho","year":"2018","journal-title":"Neurochem. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.bbadis.2016.12.007","article-title":"Allopregnanolone and its analog BR 297 rescue neuronal cells from oxidative stress-induced death through bioenergetic improvement","volume":"1863","author":"Lejri","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3786","DOI":"10.1111\/j.1582-4934.2008.00493.x","article-title":"Oxidative stress in NPC1 deficient cells: Protective effect of allopregnanolone","volume":"13","author":"Zampieri","year":"2009","journal-title":"J. Cell Mol. Med."},{"key":"ref_77","first-page":"13610","article-title":"Allopregnanolone attenuates Abeta25-35-induced neurotoxicity in PC12 cells by reducing oxidative stress","volume":"8","author":"Qian","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/S0892-0362(02)00220-9","article-title":"Diabetic neuropathies in brain are induced by deficiency of BDNF","volume":"24","author":"Nitta","year":"2002","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"102160","DOI":"10.1016\/j.jchemneu.2022.102160","article-title":"Microglia activation and inflammation in hippocampus attenuates memory and mood functions during experimentally induced diabetes in rat","volume":"125","author":"Nagayach","year":"2022","journal-title":"J. Chem. Neuroanat."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"611","DOI":"10.14336\/AD.2018.0707","article-title":"BDNF Alleviates Neuroinflammation in the Hippocampus of Type 1 Diabetic Mice via Blocking the Aberrant HMGB1\/RAGE\/NF-kappaB Pathway","volume":"10","author":"Han","year":"2019","journal-title":"Aging Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1016\/j.biopha.2018.07.063","article-title":"The protective effect of formononetin on cognitive impairment in streptozotocin (STZ)-induced diabetic mice","volume":"106","author":"Wang","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.brainresbull.2017.07.013","article-title":"The antidepressant effect of melatonin and fluoxetine in diabetic rats is associated with a reduction of the oxidative stress in the prefrontal and hippocampal cortices","volume":"134","author":"Rebai","year":"2017","journal-title":"Brain Res. Bull."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1007\/s11011-018-0264-9","article-title":"The antioxidant gallic acid induces anxiolytic-, but not antidepressant-like effect, in streptozotocin-induced diabetes","volume":"33","author":"Pereira","year":"2018","journal-title":"Metab. Brain Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1080\/17512433.2017.1293521","article-title":"Brain injury with diabetes mellitus: Evidence, mechanisms and treatment implications","volume":"10","author":"Hamed","year":"2017","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"57","DOI":"10.4103\/2008-7802.178531","article-title":"The Effect of Diabetes Mellitus on Apoptosis in Hippocampus: Cellular and Molecular Aspects","volume":"7","author":"Sadeghi","year":"2016","journal-title":"Int. J. Prev Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.jsbmb.2017.11.009","article-title":"Diabetes induces mitochondrial dysfunction and alters cholesterol homeostasis and neurosteroidogenesis in the rat cerebral cortex","volume":"178","author":"Romano","year":"2018","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"100804","DOI":"10.1016\/j.yfrne.2019.100804","article-title":"Sex differences in steroid levels and steroidogenesis in the nervous system: Physiopathological role","volume":"56","author":"Giatti","year":"2019","journal-title":"Front. Neuroendocrinol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e12736","DOI":"10.1111\/jne.12736","article-title":"Sex differences in the brain expression of steroidogenic molecules under basal conditions and after gonadectomy","volume":"31","author":"Giatti","year":"2019","journal-title":"J. Neuroendocrinol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"105364","DOI":"10.1016\/j.psyneuen.2021.105364","article-title":"Effects of paroxetine treatment and its withdrawal on neurosteroidogenesis","volume":"132","author":"Giatti","year":"2021","journal-title":"Psychoneuroendocrinology"},{"key":"ref_90","first-page":"F201","article-title":"Lipid peroxidation in isolated rat nephron segments","volume":"263","author":"Ha","year":"1992","journal-title":"Am. J. Physiol"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/2\/1196\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:02:49Z","timestamp":1760119369000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/2\/1196"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,7]]},"references-count":90,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["ijms24021196"],"URL":"https:\/\/doi.org\/10.3390\/ijms24021196","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,7]]}}}