{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T13:10:47Z","timestamp":1792761047299,"version":"4.5.0"},"reference-count":134,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T00:00:00Z","timestamp":1665446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011019","name":"Nemzeti Kutat\u00e1si Fejleszt\u00e9si \u00e9s Innov\u00e1ci\u00f3s Hivatal","doi-asserted-by":"publisher","award":["K141934,  K138763 , K 120311"],"award-info":[{"award-number":["K141934,  K138763 , K 120311"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015498","name":"Innov\u00e1ci\u00f3s \u00e9s Technol\u00f3giai Miniszt\u00e9rium","doi-asserted-by":"publisher","award":["TKP2021-EGA-16"],"award-info":[{"award-number":["TKP2021-EGA-16"]}],"id":[{"id":"10.13039\/501100015498","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Alzheimer\u2019s disease is the most common type of dementia, being highly prevalent in elderly women. The advanced progression may be due to decreased hormone synthesis during post-menopause as estradiol and progesterone both have neuroprotective potentials. We aimed to confirm that female hormone depletion aggravates the progression of dementia in a triple transgenic mouse model of Alzheimer\u2019s disease (3xTg-AD). As pathological hallmarks are known to appear in 6-month-old animals, we expected to see disease-like changes in the 4-month-old 3xTg-AD mice only after hormone depletion. Three-month-old female 3xTg-AD mice were compared with their age-matched controls. As a menopause model, ovaries were removed (OVX or Sham surgery). After 1-month recovery, the body composition of the animals was measured by an MRI scan. The cognitive and anxiety parameters were evaluated by different behavioral tests, modeling different aspects (Y-maze, Morris water maze, open-field, social discrimination, elevated plus maze, light\u2013dark box, fox odor, operant conditioning, and conditioned fear test). At the end of the experiment, uterus was collected, amyloid-\u03b2 accumulation, and the cholinergic system in the brain was examined by immunohistochemistry. The uterus weight decreased, and the body weight increased significantly in the OVX animals. The MRI data showed that the body weight change can be due to fat accumulation. Moreover, OVX increased anxiety in control, but decreased in 3xTg-AD animals, the later genotype being more anxious by default based on the anxiety z-score. In general, 3xTg-AD mice moved less. In relation to cognition, neither the 3xTg-AD genotype nor OVX surgery impaired learning and memory in general. Despite no progression of dementia-like behavior after OVX, at the\u00a0histological level, OVX aggravated the amyloid-\u03b2 plaque deposition in the basolateral amygdala and induced early cholinergic neuronal fiber loss in the somatosensory cortex of the transgenic animals. We confirmed that OVX induced menopausal symptoms. Removal of the sexual steroids aggravated the appearance of AD-related alterations in the brain without significantly affecting the behavior. Thus, the OVX in young, 3-month-old 3xTg-AD mice might be a suitable model for testing the effect of new treatment options on structural changes; however, to reveal any beneficial effect on behavior, a later time point might be needed.<\/jats:p>","DOI":"10.3389\/fendo.2022.985424","type":"journal-article","created":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T09:53:21Z","timestamp":1665482001000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["Ovariectomy-induced hormone deprivation aggravates A\u03b21-42 deposition in the basolateral amygdala and cholinergic fiber loss in the cortex but not cognitive behavioral symptoms in a triple transgenic mouse model of Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"13","author":[{"given":"Szid\u00f3nia","family":"Farkas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienn","family":"Szab\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bibi\u00e1na","family":"T\u00f6r\u00f6k","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Csenge","family":"S\u00f3lyomv\u00e1ri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Csilla Lea","family":"Fazekas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krisztina","family":"B\u00e1nr\u00e9vi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Correia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiago","family":"Chaves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00f3ra","family":"Zelena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1002\/alz.12068","article-title":"2020 alzheimer\u2019s disease facts and figures","volume":"16","year":"2020","journal-title":"Alzheimer\u2019s Dement"},{"key":"B2","unstructured":"The top 10 causes of death2020"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.05.2410","article-title":"Neuropsychiatric symptoms in alzheimer\u2019s disease","volume":"7","author":"Lyketsos","year":"2011","journal-title":"Alzheimers Dement"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)01124-1","article-title":"Alzheimer\u2019s disease","volume":"388","author":"Scheltens","year":"2016","journal-title":"Lancet (London England)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2005.02.009","article-title":"Alzheimer\u2019s disease: Abeta, tau and synaptic dysfunction","volume":"11","author":"LaFerla","year":"2005","journal-title":"Trends Mol Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0909142","article-title":"Alzheimer\u2019s disease","volume":"362","author":"Querfurth","year":"2010","journal-title":"N Engl J Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.04.008","article-title":"Understanding the impact of sex and gender in alzheimer\u2019s disease: A call to action","volume":"14","author":"Nebel","year":"2018","journal-title":"Alzheimers Dement"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.01.012","article-title":"Molecular genetics of early-onset alzheimer\u2019s disease revisited","volume":"12","author":"Cacace","year":"2016","journal-title":"Alzheimers Dement"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2016.01.011","article-title":"Identifying postmenopausal women at risk for cognitive decline within a healthy cohort using a panel of clinical metabolic indicators: potential for detecting an at-alzheimer\u2019s risk metabolic phenotype","volume":"40","author":"Rettberg","year":"2016","journal-title":"Neurobiol Aging"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.04.004","article-title":"Sexual dimorphism in predisposition to alzheimer\u2019s disease","volume":"70","author":"Fisher","year":"2018","journal-title":"Neurobiol Aging"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23827","article-title":"Sex and the development of alzheimer\u2019s disease","volume":"95","author":"Pike","year":"2017","journal-title":"J Neurosci Res"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2000.17.367","article-title":"Gender differences in acute CNS trauma and stroke: neuroprotective effects of estrogen and progesterone","volume":"17","author":"Roof","year":"2000","journal-title":"J Neurotrauma"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2011.03.001","article-title":"Ovarian hormone loss induces bioenergetic deficits and mitochondrial \u03b2-amyloid","volume":"33","author":"Yao","year":"2012","journal-title":"Neurobiol Aging"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001776","article-title":"Estrogen actions in the nervous system: Complexity and clinical implications","volume":"85","author":"Cersosimo","year":"2015","journal-title":"Neurology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.neuroscience.2012.10.038","article-title":"Estrogen promotes learning-related plasticity by modifying the synaptic cytoskeleton","volume":"239","author":"Kram\u00e1r","year":"2013","journal-title":"Neuroscience"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00137","article-title":"Rapid modulation of synaptogenesis and spinogenesis by 17\u03b2-estradiol in primary cortical neurons","volume":"9","author":"Sellers","year":"2015","journal-title":"Front Cell Neurosci"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/srep21101","article-title":"Treatment of beta amyloid 1-42 (Abeta(1-42))-induced basal forebrain cholinergic damage by a non-classical estrogen signaling activator in vivo","volume":"6","author":"Kwakowsky","year":"2016","journal-title":"Sci Rep"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00489.2020","article-title":"Examining the effects of ovarian hormone loss and diet-induced obesity on alzheimer\u2019s disease markers of amyloid-\u03b2 production and degradation","volume":"125","author":"Hayward","year":"2021","journal-title":"J Neurophysiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.00240","article-title":"Estradiol replacement at the critical period protects hippocampal neural stem cells to improve cognition in APP\/PS1 mice","volume":"12","author":"Qin","year":"2020","journal-title":"Front Aging Neurosci"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004425","article-title":"Sex differences in Alzheimer risk: Brain imaging of endocrine vs chronologic aging","volume":"89","author":"Mosconi","year":"2017","journal-title":"Neurology"},{"key":"B21","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/J.PSYNEUEN.2019.03.013","article-title":"Surgical menopause in association with cognitive function and risk of dementia: A systematic review and meta-analysis","volume":"106","author":"Georgakis","year":"2019","journal-title":"Psychoneuroendocrinology"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000276984.19542.E6","article-title":"Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause","volume":"69","author":"Rocca","year":"2007","journal-title":"Neurology"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.2217\/WHE.09.42","article-title":"Effect of bilateral oophorectomy on women\u2019s long-term health","volume":"5","author":"Parker","year":"2009","journal-title":"Womens Health (Lond Engl)"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1210\/EN.2012-1340","article-title":"Minireview: Translational animal models of human menopause: Challenges and emerging opportunities","volume":"153","author":"Brinton","year":"2012","journal-title":"Endocrinology"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEUROBIOLAGING.2021.02.011","article-title":"Long-term ovarian hormone deprivation alters functional connectivity, brain neurochemical profile and white matter integrity in the Tg2576 amyloid mouse model of alzheimer\u2019s disease","volume":"102","author":"Kara","year":"2021","journal-title":"Neurobiol Aging"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1126\/science.8346443","article-title":"Gene dose of apolipoprotein e type 4 allele and the risk of alzheimer\u2019s disease in late onset families","volume":"261","author":"Corder","year":"1993","journal-title":"Science"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.622209","article-title":"Role of apolipoprotein e in \u03b2-amyloidogenesis: Isoform-specific effects on protofibril to fibril conversion of a\u03b2 in vitro and brain a\u03b2 deposition in vivo","volume":"290","author":"Hori","year":"2015","journal-title":"J Biol Chem"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1542-12.2012","article-title":"Especially apolipoprotein E4, increases the oligomerization of amyloid \u03b2 peptide","volume":"32","author":"Hashimoto","year":"2012","journal-title":"J Neurosci"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1016\/j.neuron.2017.11.013","article-title":"ApoE4 accelerates early seeding of amyloid pathology","volume":"96","author":"Liu","year":"2017","journal-title":"Neuron"},{"key":"B30","doi-asserted-by":"publisher","first-page":"89ra57","DOI":"10.1126\/scitranslmed.3002156","article-title":"Human apoE isoforms differentially regulate brain amyloid-\u03b2 peptide clearance","volume":"3","author":"Castellano","year":"2011","journal-title":"Sci Transl Med"},{"key":"B31","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1038\/s41551-021-00759-0","article-title":"Brain-wide Cas9-mediated cleavage of a gene causing familial alzheimer\u2019s disease alleviates amyloid-related pathologies in mice","volume":"6","author":"Duan","year":"2021","journal-title":"Nat BioMed Eng"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002270","article-title":"APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases","volume":"14","author":"Lanoisel\u00e9e","year":"2017","journal-title":"PloS Med"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/nature11283","article-title":"A mutation in APP protects against alzheimer\u2019s disease and age-related cognitive decline","volume":"488","author":"Jonsson","year":"2012","journal-title":"Nature"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.69020834.x","article-title":"Two-dimensional characterization of paired helical filament-tau from alzheimer\u2019s disease: demonstration of an additional 74-kDa component and age-related biochemical modifications","volume":"69","author":"Sergeant","year":"1997","journal-title":"J Neurochem"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90117-V","article-title":"Tau proteins of alzheimer paired helical filaments: Abnormal phosphorylation of all six brain isoforms","volume":"8","author":"Goedert","year":"1992","journal-title":"Neuron"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/s0896-6273(03)00434-3","article-title":"Triple-transgenic model of alzheimer\u2019s disease with plaques and tangles: intracellular abeta and synaptic dysfunction","volume":"39","author":"Oddo","year":"2003","journal-title":"Neuron"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2003.08.012","article-title":"Amyloid deposition precedes tangle formation in a triple transgenic model of alzheimer\u2019s disease","volume":"24","author":"Oddo","year":"2003","journal-title":"Neurobiol Aging"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12873","article-title":"Temporal and regional progression of alzheimer\u2019s disease-like pathology in 3xTg-AD mice","volume":"18","author":"Belfiore","year":"2019","journal-title":"Aging Cell"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.09.006","article-title":"Basal forebrain cholinergic circuits and signaling in cognition and cognitive decline","volume":"91","author":"Ballinger","year":"2016","journal-title":"Neuron"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1676-18.2018","article-title":"Specific basal forebrain-cortical cholinergic circuits coordinate cognitive operations","volume":"38","author":"Z\u00e1borszky","year":"2018","journal-title":"J Neurosci"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1126\/SCIENCE.7058341","article-title":"Alzheimer\u2019s disease and senile dementia: loss of neurons in the basal forebrain","volume":"215","author":"Whitehouse","year":"1982","journal-title":"Science"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/ncomms13249","article-title":"Basal forebrain degeneration precedes and predicts the cortical spread of alzheimer\u2019s pathology","volume":"7","author":"Schmitz","year":"2016","journal-title":"Nat Commun 2016 71"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2010.105","article-title":"Clinical use of cholinergic drugs in Alzheimer disease","volume":"6","author":"Desmarais","year":"2010","journal-title":"Nat Rev Neurol 2010 68"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1111\/J.1460-9568.2005.03953.X","article-title":"The effect of aging on the subcellular distribution of estrogen receptor-alpha in the cholinergic neurons of transgenic and wild-type mice","volume":"21","author":"Kalesnykas","year":"2005","journal-title":"Eur J Neurosci"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1111\/JNE.12830","article-title":"Sex differences in rapid nonclassical action of 17\u03b2-oestradiol on intracellular signalling and oestrogen receptor \u03b1 expression in basal forebrain cholinergic neurones in mouse","volume":"32","author":"Kim","year":"2020","journal-title":"J Neuroendocrinol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1111\/jne.12837","article-title":"The G protein-coupled oestrogen receptor, GPER1, mediates direct anti-inflammatory effects of oestrogens in human cholinergic neurones from the nucleus basalis of meynert","volume":"32","author":"Sarchielli","year":"2020","journal-title":"J Neuroendocrinol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1210\/EN.2002-221069","article-title":"Immunolocalization of estrogen receptor \u03b2 in the mouse brain: Comparison with estrogen receptor \u03b1","volume":"144","author":"Mitra","year":"2003","journal-title":"Endocrinology"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1002\/CNE.20128","article-title":"Distribution of estrogen receptor alpha and beta in the mouse central nervous system: in vivo autoradiographic and immunocytochemical analyses","volume":"473","author":"Merchenthaler","year":"2004","journal-title":"J Comp Neurol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1002\/JNR.21609","article-title":"Effects of estrogen on basal forebrain cholinergic neurons and spatial learning","volume":"86","author":"Ping","year":"2008","journal-title":"J Neurosci Res"},{"key":"B50","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/J.NEULET.2005.09.023","article-title":"Estrogen contributes to structural recovery after a lesion","volume":"392","author":"Saenz","year":"2006","journal-title":"Neurosci Lett"},{"key":"B51","doi-asserted-by":"publisher","first-page":"S104","DOI":"10.1016\/j.psyneuen.2009.05.024","article-title":"Action of estrogen on survival of basal forebrain cholinergic neurons: Promoting amelioration","volume":"34","author":"\u00c1brah\u00e1m","year":"2009","journal-title":"Psychoneuroendocrinology"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/J.NBD.2010.10.002","article-title":"Cholinotrophic basal forebrain system alterations in 3xTg-AD transgenic mice","volume":"41","author":"Perez","year":"2011","journal-title":"Neurobiol Dis"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-021-03830-w","article-title":"Alzheimer\u2019s pathogenic mechanisms and underlying sex difference","volume":"78","author":"Zhu","year":"2021","journal-title":"Cell Mol Life Sci"},{"key":"B54","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/J.TEM.2010.10.002","article-title":"Estrogen and androgen receptors: regulators of fuel homeostasis and emerging targets for diabetes and obesity","volume":"22","author":"Mauvais-Jarvis","year":"2011","journal-title":"Trends Endocrinol Metab"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1073\/PNAS.94.12.6535","article-title":"Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine epithelium","volume":"94","author":"Cooke","year":"1997","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1080\/21688370.2020.1865760","article-title":"Ovariectomized mice and postmenopausal women exhibit analogous loss of genital epithelial integrity","volume":"9","author":"Quispe Calla","year":"2021","journal-title":"Tissue Barriers"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2019.112688","article-title":"Consequences of VGluT3 deficiency on learning and memory in mice","volume":"212","author":"Fazekas","year":"2019","journal-title":"Physiol Behav"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.21769\/BIOPROTOC.3162","article-title":"Assessing spatial working memory using the spontaneous alternation y-maze test in aged Male mice","volume":"9","author":"Prieur","year":"2019","journal-title":"Bio-protocol"},{"key":"B59","doi-asserted-by":"publisher","first-page":"29","DOI":"10.3109\/00207458909002151","article-title":"The use of the morris water maze in the study of memory and learning","volume":"48","author":"Brandeis","year":"1989","journal-title":"Int J Neurosci"},{"key":"B60","doi-asserted-by":"publisher","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":"B61","doi-asserted-by":"publisher","DOI":"10.3389\/FNAGI.2021.718949","article-title":"Neuropsychiatric profile as a predictor of cognitive decline in mild cognitive impairment","volume":"13","author":"Roberto","year":"2021","journal-title":"Front Aging Neurosci"},{"key":"B62","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/J.NEUROBIOLAGING.2019.10.008","article-title":"Apathy and anxiety are early markers of alzheimer\u2019s disease","volume":"85","author":"Johansson","year":"2020","journal-title":"Neurobiol Aging"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1097\/GME.0000000000001229","article-title":"Long-term risk of depressive and anxiety symptoms after early bilateral oophorectomy","volume":"25","author":"Rocca","year":"2018","journal-title":"Menopause"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-7634(96)00058-9","article-title":"Anxiety, defence and the elevated plus-maze","volume":"21","author":"Rodgers","year":"1997","journal-title":"Neurosci Biobehav Rev"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/J.YHBEH.2006.01.006","article-title":"Reproductive experience alters anxiety-like behavior in the female rat","volume":"50","author":"Byrnes","year":"2006","journal-title":"Horm Behav"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/J.BRAINRES.2021.147437","article-title":"Age and gender differences for the behavioral phenotypes of 3xTg alzheimer\u2019s disease mice","volume":"1762","author":"Pairojana","year":"2021","journal-title":"Brain Res"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1093\/ILAR.45.4.401\/2\/ILAR-45-4-401IGF7.GIF","article-title":"Selecting the appropriate rodent diet for endocrine disruptor research and testing studies","volume":"45","author":"Thigpen","year":"2004","journal-title":"ILAR J"},{"key":"B68","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1095\/BIOLREPROD28.3.598","article-title":"Aging and the regulation of luteinizing hormone in C57BL\/6J mice: impaired elevations after ovariectomy and spontaneous elevations at advanced ages","volume":"28","author":"Gee","year":"1983","journal-title":"Biol Reprod"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/J.LFS.2021.120223","article-title":"Median raphe region GABAergic neurons contribute to social interest in mouse","volume":"289","author":"Chaves","year":"2022","journal-title":"Life Sci"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1038\/NPROT.2011.353","article-title":"Testing declarative memory in laboratory rats and mice using the nonconditioned social discrimination procedure","volume":"6","author":"Engelmann","year":"2011","journal-title":"Nat Protoc"},{"key":"B71","doi-asserted-by":"crossref","unstructured":"AliczkiM\n            FodorA\n            BaloghZ\n            HallerJ\n          Behavior DZ-h and, 2014 undefined. the effects of lactation on impulsive behavior in vasopressin-deficient brattleboro rats","DOI":"10.1016\/j.yhbeh.2014.08.002"},{"key":"B72","doi-asserted-by":"publisher","first-page":"1982","DOI":"10.1523\/JNEUROSCI.1944-20.2020","article-title":"Somatostatin neurons of the bed nucleus of stria terminalis enhance associative fear memory consolidation in mice","volume":"41","author":"Bruzsik","year":"2021","journal-title":"J Neurosci"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1080\/10253890.2017.1423053","article-title":"Enhanced innate fear and altered stress axis regulation in VGluT3 knockout mice","volume":"21","author":"Bal\u00e1zsfi","year":"2018","journal-title":"Stress"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.3390\/biom10050801","article-title":"Effects of chronic cannabidiol treatment in the rat chronic unpredictable mild stress model of depression","volume":"10","author":"G\u00e1ll","year":"2020","journal-title":"Biomolecules"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/J.YNSTR.2021.100415","article-title":"Neurochemically distinct populations of the bed nucleus of stria terminalis modulate innate fear response to weak threat evoked by predator odor stimuli","volume":"15","author":"Bruzsik","year":"2021","journal-title":"Neurobiol Stress"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1001\/JAMANEUROL.2019.3606","article-title":"Selective vulnerability of the nucleus basalis of meynert among neuropathologic subtypes of Alzheimer disease","volume":"77","author":"Hanna Al-Shaikh","year":"2020","journal-title":"JAMA Neurol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0876-20.2020","article-title":"Implications of oligomeric amyloid-beta (oA\u03b2 42) signaling through \u03b17\u03b22-nicotinic acetylcholine receptors (nAChRs) on basal forebrain cholinergic neuronal intrinsic excitability and cognitive decline","volume":"41","author":"George","year":"2021","journal-title":"J Neurosci"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(80)90195-5","article-title":"The nucleus basalis magnocellularis: the origin of a cholinergic projection to the neocortex of the rat","volume":"5","author":"Lehmann","year":"1980","journal-title":"Neuroscience"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1210\/en.2011-1017","article-title":"Postlesion estradiol treatment increases cortical cholinergic innervations via estrogen receptor-\u03b1 dependent nonclassical estrogen signaling in vivo","volume":"152","author":"Koszegi","year":"2011","journal-title":"Endocrinology"},{"key":"B80","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/J.JNEUMETH.2011.01.019","article-title":"Integrated behavioral z-scoring increases the sensitivity and reliability of behavioral phenotyping in mice: relevance to emotionality and sex","volume":"197","author":"Guilloux","year":"2011","journal-title":"J Neurosci Methods"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1080\/10253890.2020.1795121","article-title":"Searching for glycomic biomarkers for predicting resilience and vulnerability in a rat model of posttraumatic stress disorder","volume":"23","author":"Fazekas","year":"2020","journal-title":"Stress"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1073\/PNAS.97.23.12729","article-title":"Increased adipose tissue in male and female estrogen receptor-alpha knockout mice","volume":"97","author":"Heine","year":"2000","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1111\/J.1749-6632.1977.TB29435.X","article-title":"Effect of progestins on glucose and lipid metabolism","volume":"286","author":"Beck","year":"1977","journal-title":"Ann N Y Acad Sci"},{"key":"B84","doi-asserted-by":"publisher","first-page":"14750","DOI":"10.1038\/S41598-021-94189-2","article-title":"Changes in abdominal subcutaneous adipose tissue phenotype following menopause is associated with increased visceral fat mass","volume":"11","author":"Abildgaard","year":"2021","journal-title":"Sci Rep"},{"key":"B85","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/J.AJOG.2019.04.023","article-title":"Fat mass changes during menopause: a metaanalysis","volume":"221","author":"Ambikairajah","year":"2019","journal-title":"Am J Obstet Gynecol"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1111\/EJN.14758","article-title":"Obesity and alzheimer\u2019s disease: Molecular bases","volume":"52","author":"Picone","year":"2020","journal-title":"Eur J Neurosci"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.3349\/YMJ.2017.58.3.479","article-title":"Metabolism-centric overview of the pathogenesis of alzheimer\u2019s disease","volume":"58","author":"Kang","year":"2017","journal-title":"Yonsei Med J"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1007\/S11010-020-03879-4","article-title":"Ovariectomized rodents as a menopausal metabolic syndrome model. a minireview","volume":"475","author":"Medina-Contreras","year":"2020","journal-title":"Mol Cell Biochem"},{"key":"B89","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/J.DIFF.2021.01.002","article-title":"Molecular mechanisms of estrogen action in female genital tract development","volume":"118","author":"Alderman","year":"2021","journal-title":"Differentiation"},{"key":"B90","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.steroids.2017.10.014","article-title":"Membrane estrogen receptors signal to determine transcription factor function","volume":"132","author":"Levin","year":"2018","journal-title":"Steroids"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1333-12.2012","article-title":"The role of cAMP response element-binding protein in estrogen negative feedback control of gonadotropin-releasing hormone neurons","volume":"32","author":"Kwakowsky","year":"2012","journal-title":"J Neurosci"},{"key":"B92","doi-asserted-by":"publisher","first-page":"14533","DOI":"10.1523\/JNEUROSCI.1776-15.2015","article-title":"Expression of ESR1 in glutamatergic and GABAergic neurons is essential for normal puberty onset, estrogen feedback, and fertility in female mice","volume":"35","author":"Cheong","year":"2015","journal-title":"J Neurosci"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1210\/ENDOCR\/BQAA237","article-title":"Indirect suppression of pulsatile LH secretion by CRH neurons in the female mouse","volume":"162","author":"Yip","year":"2021","journal-title":"Endocrinology"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.3390\/BIOMEDICINES10040861","article-title":"Estradiol and estrogen-like alternative therapies in use: The importance of the selective and non-classical actions","volume":"10","author":"Farkas","year":"2022","journal-title":"Biomedicines"},{"key":"B95","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/IJMS21218301","article-title":"Effects of estrogen receptor and wnt signaling activation on mechanically induced bone formation in a mouse model of postmenopausal bone loss","volume":"21","author":"Liedert","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.3390\/BIOM12010041","article-title":"Metabolomics coupled with pathway analysis provides insights into sarco-osteoporosis metabolic alterations and estrogen therapeutic effects in mice","volume":"12","author":"Wei","year":"2021","journal-title":"Biomolecules"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.3389\/FGENE.2014.00088","article-title":"Using mice to model alzheimer\u2019s dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models","volume":"5","author":"Webster","year":"2014","journal-title":"Front Genet"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1590\/1516-4446-2013-1139","article-title":"Animal models of anxiety disorders and stress","volume":"35","author":"Campos","year":"2013","journal-title":"Rev Bras Psiquiatr"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-180173","article-title":"A study of amyloid-\u03b2 and phosphotau in plaques and neurons in the hippocampus of alzheimer\u2019s disease patients","volume":"64","author":"Furcila","year":"2018","journal-title":"J Alzheimers Dis"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.32598\/BCN.2021.2634.1","article-title":"\u03b2-amyloid formation, memory, and learning decline following long-term ovariectomy and its inhibition by systemic administration of apigenin and \u03b2-estradiol","volume":"12","author":"Behnamedin","year":"2021","journal-title":"Basic Clin Neurosci"},{"key":"B101","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/J.BBR.2015.04.012","article-title":"Early detection of cognitive deficits in the 3xTg-AD mouse model of alzheimer\u2019s disease","volume":"289","author":"Stover","year":"2015","journal-title":"Behav Brain Res"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1007\/S11920-015-0636-3","article-title":"Diagnosis and treatment of anxiety in the aging woman","volume":"17","author":"Siegel","year":"2015","journal-title":"Curr Psychiatry Rep"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1007\/S10072-022-06068-X","article-title":"Anxiety and depression in alzheimer\u2019s disease: a systematic review of pathogenetic mechanisms and relation to cognitive decline","volume":"43","author":"Botto","year":"2022","journal-title":"Neurol Sci"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1016\/J.BBR.2013.05.035","article-title":"Use of the light\/dark test for anxiety in adult and adolescent male rats","volume":"256","author":"Arrant","year":"2013","journal-title":"Behav Brain Res"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1038\/NATURE15698","article-title":"Basomedial amygdala mediates top-down control of anxiety and fear","volume":"527","author":"Adhikari","year":"2015","journal-title":"Nature"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1080\/10253890.2018.1438405","article-title":"Exploratory rearing: a context- and stress-sensitive behavior recorded in the open-field test","volume":"21","author":"Sturman","year":"2018","journal-title":"Stress"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1038\/NATURE14188","article-title":"From circuits to behaviour in the amygdala","volume":"517","author":"Janak","year":"2015","journal-title":"Nature"},{"key":"B108","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/J.NEURON.2017.09.013","article-title":"Fear, anxiety, and the amygdala","volume":"96","author":"Sah","year":"2017","journal-title":"Neuron"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1001\/ARCHGENPSYCHIATRY.2009.104","article-title":"Disrupted amygdalar subregion functional connectivity and evidence of a compensatory network in generalized anxiety disorder","volume":"66","author":"Etkin","year":"2009","journal-title":"Arch Gen Psychiatry"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.2174\/1567205018666210823095603","article-title":"The relationship of anxiety with alzheimer\u2019s disease: A narrative review","volume":"18","author":"Patel","year":"2021","journal-title":"Curr Alzheimer Res"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1016\/J.JAD.2015.09.069","article-title":"The prevalence of neuropsychiatric symptoms in alzheimer\u2019s disease: Systematic review and meta-analysis","volume":"190","author":"Zhao","year":"2016","journal-title":"J Affect Disord"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.2174\/1567205017666200818193916","article-title":"Impaired cognitive function is associated with motor function and activities of daily living in mild to moderate alzheimer\u2019s dementia","volume":"17","author":"Lee","year":"2020","journal-title":"Curr Alzheimer Res"},{"key":"B113","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/J.JALZ.2014.04.514","article-title":"At The interface of sensory and motor dysfunctions and alzheimer\u2019s disease","volume":"11","author":"Albers","year":"2015","journal-title":"Alzheimers Dement"},{"key":"B114","doi-asserted-by":"publisher","first-page":"196.e29","DOI":"10.1016\/J.NEUROBIOLAGING.2010.05.027","article-title":"Motor deficits, neuron loss, and reduced anxiety coinciding with axonal degeneration and intraneuronal a\u03b2 aggregation in the 5XFAD mouse model of alzheimer\u2019s disease","volume":"33","author":"Jawhar","year":"2012","journal-title":"Neurobiol Aging"},{"key":"B115","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/J.PHYSBEH.2017.10.002","article-title":"Ovariectomy influences the circadian rhythm of locomotor activity and the photic phase shifts in the volcano mouse","volume":"182","author":"Ju\u00e1rez-Tapia","year":"2017","journal-title":"Physiol Behav"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1210\/EN.2014-1101","article-title":"ESR1 and ESR2 differentially regulate daily and circadian activity rhythms in female mice","volume":"155","author":"Royston","year":"2014","journal-title":"Endocrinology"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0418-20.2020","article-title":"Neuronal network excitability in alzheimer\u2019s disease: The puzzle of similar versus divergent roles of amyloid \u03b2 and tau","volume":"8","author":"Kazim","year":"2021","journal-title":"eNeuro"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000033","article-title":"Age at surgical menopause influences cognitive decline and Alzheimer pathology in older women","volume":"82","author":"Bove","year":"2014","journal-title":"Neurology"},{"key":"B119","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-021-90084-y","article-title":"Menopause impacts human brain structure, connectivity, energy metabolism, and amyloid-beta deposition","volume":"11","author":"Mosconi","year":"2021","journal-title":"Sci Rep 2021 111"},{"key":"B120","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1001\/JAMANEUROL.2018.3057","article-title":"Association of bilateral salpingo-oophorectomy before menopause onset with medial temporal lobe neurodegeneration","volume":"76","author":"Zeydan","year":"2019","journal-title":"JAMA Neurol"},{"key":"B121","doi-asserted-by":"publisher","first-page":"13357","DOI":"10.1523\/JNEUROSCI.2718-07.2007","article-title":"Progesterone and estrogen regulate Alzheimer-like neuropathology in female 3xTg-AD mice","volume":"27","author":"Carroll","year":"2007","journal-title":"J Neurosci"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEUROBIOLAGING.2009.12.010","article-title":"17\u03b2-estradiol regulates insulin-degrading enzyme expression via an ER\u03b2\/PI3-K pathway in hippocampus: relevance to alzheimer\u2019s prevention","volume":"32","author":"Zhao","year":"2011","journal-title":"Neurobiol Aging"},{"key":"B123","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1111\/JNC.12706","article-title":"Down-regulation of serum gonadotropins but not estrogen replacement improves cognition in aged-ovariectomized 3xTg AD female mice","volume":"130","author":"Palm","year":"2014","journal-title":"J Neurochem"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1016\/J.BIOPSYCH.2008.09.003","article-title":"Disruption of fear memory through dual-hormone gene therapy","volume":"65","author":"Rodrigues","year":"2009","journal-title":"Biol Psychiatry"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1093\/CERCOR\/BHQ003","article-title":"Estrogen promotes stress sensitivity in a prefrontal cortex-amygdala pathway","volume":"20","author":"Shansky","year":"2010","journal-title":"Cereb Cortex"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1016\/J.PSYNEUEN.2013.04.011","article-title":"Estrogen receptor GPR30 exerts anxiolytic effects by maintaining the balance between GABAergic and glutamatergic transmission in the basolateral amygdala of ovariectomized mice after stress","volume":"38","author":"Tian","year":"2013","journal-title":"Psychoneuroendocrinology"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1210\/EN.2004-1433","article-title":"Estrogen therapy fails to alter amyloid deposition in the PDAPP model of alzheimer\u2019s disease","volume":"146","author":"Green","year":"2005","journal-title":"Endocrinology"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PONE.0059825","article-title":"Ovariectomy induces a shift in fuel availability and metabolism in the hippocampus of the female transgenic model of familial alzheimer\u2019s","volume":"8","author":"Ding","year":"2013","journal-title":"PloS One"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2002-4601","article-title":"17Alpha-estradiol and 17beta-estradiol treatments are effective in lowering cerebral amyloid-beta levels in AbetaPPSWE transgenic mice","volume":"4","author":"Levin-Allerhand","year":"2002","journal-title":"J Alzheimers Dis"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1093\/ABBS\/GMY032","article-title":"Effects of ovarian hormone loss on neuritic plaques and autophagic flux in the brains of adult female APP\/PS1 double-transgenic mice","volume":"50","author":"Yao","year":"2018","journal-title":"Acta Biochim Biophys Sin (Shanghai)"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy132","article-title":"The cholinergic system in the pathophysiology and treatment of alzheimer\u2019s disease","volume":"141","author":"Hampel","year":"2018","journal-title":"Brain"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.3390\/MOLECULES27061816","article-title":"Role of cholinergic signaling in alzheimer\u2019s disease","volume":"27","author":"Chen","year":"2022","journal-title":"Molecules"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1046\/J.1365-2826.2003.01012.X","article-title":"Effects of ageing and long-term hormone replacement on cholinergic neurones in the medial septum and nucleus basalis magnocellularis of ovariectomized rats","volume":"15","author":"Gibbs","year":"2003","journal-title":"J Neuroendocrinol"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1202-06.2006","article-title":"Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial alzheimer\u2019s disease mutations: potential factors in amyloid plaque formation","volume":"26","author":"Oakley","year":"2006","journal-title":"J Neurosci"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.985424\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T09:53:27Z","timestamp":1665482007000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.985424\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,11]]},"references-count":134,"alternative-id":["10.3389\/fendo.2022.985424"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.985424","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,11]]},"article-number":"985424"}}