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Neuroinflammation and stress activate peripheral immune mechanisms, which may contribute to the development of depression and anxiety in sporadic Alzheimer\u2019s disease (sAD). This study aims to evaluate whether intracerebroventricular (ICV) premedication with IGF-1 in a rat model of streptozotocin (STZ)-induced neuroinflammation can prevent the emergence of anhedonia and anxiety-like behavior by impacting the peripheral inflammatory responses. (2) Male Wistar rats were subjected to double ICVSTZ (total dose: 3 mg\/kg) and ICVIGF-1 injections (total dose: 2 \u00b5g). We analyzed the level of anhedonia (sucrose preference), anxiety (elevated plus maze), peripheral inflammation (hematological and cytometric measurement of leukocyte populations, interleukin (IL)-6), and corticosterone concentration at 7 (very early stage, VES), 45 (early stage, ES), and 90 days after STZ injections (late stage, LS). (3) We found that ICVIGF-1 administration reduces behavioral symptoms: anhedonia (ES and LS) and anxiety (VES, ES), and peripheral inflammation: number of leukocytes, lymphocytes, T lymphocytes, monocytes, granulocytes, IL-6, and corticosterone concentration (LS) in the rat model of sAD. (4) The obtained results demonstrate beneficial effects of central IGF-1 administration on neuropsychiatric symptoms and peripheral immune system activation during disease progression in the rat model of sAD.<\/jats:p>","DOI":"10.3390\/cells14151189","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T09:41:17Z","timestamp":1754300477000},"page":"1189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Central Insulin-Like Growth Factor-1-Induced Anxiolytic and Antidepressant Effects in a Rat Model of Sporadic Alzheimer\u2019s Disease Are Associated with the Peripheral Suppression of Inflammation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8454-1012","authenticated-orcid":false,"given":"Joanna","family":"Dunacka","sequence":"first","affiliation":[{"name":"Department of Animal and Human Physiology, Faculty of Biology, University of Gdansk, Wita Stwosza 59 Street, 80-308 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6352-5582","authenticated-orcid":false,"given":"Beata","family":"Grembecka","sequence":"additional","affiliation":[{"name":"Department of Animal and Human Physiology, Faculty of Biology, University of Gdansk, Wita Stwosza 59 Street, 80-308 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3859-9966","authenticated-orcid":false,"given":"Danuta","family":"Wrona","sequence":"additional","affiliation":[{"name":"Department of Animal and Human Physiology, Faculty of Biology, University of Gdansk, Wita Stwosza 59 Street, 80-308 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41392-024-01911-3","article-title":"Recent advances in Alzheimer\u2019s disease: Mechanisms, clinical trials and new drug development strategies","volume":"9","author":"Zhang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1212\/CON.0000000000000700","article-title":"Late-onset Alzheimer Disease","volume":"25","author":"Rabinovici","year":"2019","journal-title":"Contin. Lifelong Learn. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.arr.2011.01.001","article-title":"Insulin-resistant brain state: The culprit in sporadic Alzheimer\u2019s disease?","volume":"10","author":"Correia","year":"2011","journal-title":"Ageing Res. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Buccellato, F.R., D\u2019Anca, M., Serpente, M., Arighi, A., and Galimberti, D. (2022). The role of glymphatic system in Alzheimer\u2019s and Parkinson\u2019s disease pathogenesis. Biomedicines, 10.","DOI":"10.3390\/biomedicines10092261"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"519","DOI":"10.3892\/br.2016.630","article-title":"Role of oxidative stress in Alzheimer\u2019s disease","volume":"4","author":"Huang","year":"2016","journal-title":"Biomed. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s11882-013-0417-1","article-title":"Etiology and pathogenesis of late-onset Alzheimer\u2019s disease","volume":"14","author":"Balin","year":"2014","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s10571-017-0521-1","article-title":"Brain under stress and Alzheimer\u2019s disease","volume":"38","author":"Mravec","year":"2018","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"87","DOI":"10.5114\/fn.2019.85929","article-title":"Risk factors for Alzheimer\u2019s disease","volume":"57","author":"Armstrong","year":"2019","journal-title":"Folia Neuropathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"102068","DOI":"10.1016\/j.arr.2023.102068","article-title":"Alzheimer\u2019s disease as a viral disease: Revisiting the infectious hypothesis","volume":"91","author":"Bruno","year":"2023","journal-title":"Ageing Res. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s00415-024-12800-8","article-title":"Dysregulation of energy metabolism in Alzheimer\u2019s disease","volume":"272","author":"Yuan","year":"2024","journal-title":"J. Neurol."},{"key":"ref_11","unstructured":"Sharan, P., and Vellapandian, C. (2024). Hypothalamic-Pituitary-Adrenal (HPA) axis: Unveiling the potential mechanisms involved in stress-induced Alzheimer\u2019s disease and depression. Cureus, 16."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Passeri, E., Elkhoury, K., Morsink, M., Broersen, K., Linder, M., Tamayol, A., Malaplate, C., Yen, F.T., and Arab-Tehrany, E. (2022). Alzheimer\u2019s disease: Treatment strategies and their limitations. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232213954"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/13543784.2023.2178414","article-title":"Lecanemab (BAN2401): An anti-beta-amyloid monoclonal antibody for the treatment of Alzheimer disease","volume":"32","author":"Vitek","year":"2023","journal-title":"Expert. Opin. Investig. Drugs"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4548","DOI":"10.1007\/s12035-015-9384-y","article-title":"Streptozotocin intracerebroventricular-induced neurotoxicity and brain insulin resistance: A therapeutic intervention for treatment of sporadic Alzheimer\u2019s disease (sAD)-like pathology","volume":"53","author":"Kamat","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_15","first-page":"594","article-title":"The mechanism underlying streptozotocin injection for the development of a nontransgenic Alzheimer\u2019s disease animal model","volume":"15","author":"Titisari","year":"2025","journal-title":"Open Vet. J."},{"key":"ref_16","first-page":"217","article-title":"Central insulin resistance as a trigger for sporadic Alzheimer-like pathology: An experimental approach","volume":"72","author":"Hoyer","year":"2007","journal-title":"J. Neural. Transm. Suppl."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3233\/JAD-2012-120958","article-title":"Streptozotocin-induced sporadic Alzheimer\u2019s disease: Selection of appropriate dose","volume":"33","author":"Mehla","year":"2013","journal-title":"J. Alzheimer Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.bbr.2016.04.012","article-title":"Dimethyl fumarate attenuates intracerebroventricular streptozotocin-induced spatial memory impairment and hippocampal neurodegeneration in rats","volume":"308","author":"Majkutewicz","year":"2016","journal-title":"Behav. Brain Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.brainres.2018.02.016","article-title":"Age-dependent effects of dimethyl fumarate on cognitive and neuropathological features in the streptozotocin-induced rat model of Alzheimer\u2019s disease","volume":"1686","author":"Majkutewicz","year":"2018","journal-title":"Brain Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Dunacka, J., \u015awi\u0105tek, G., and Wrona, D. (2024). High behavioral reactivity to novelty as a susceptibility factor for memory and anxiety disorders in streptozotocin-induced neuroinflammation as a rat model of Alzheimer\u2019s disease. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252111562"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"113595","DOI":"10.1016\/j.physbeh.2021.113595","article-title":"Treadmill exercise sex-dependently alters susceptibility to depression-like behaviour, cytokines and BDNF in the hippocampus and prefrontal cortex of rats with sporadic Alzheimer-like disease","volume":"241","author":"Naghibi","year":"2021","journal-title":"Physiol. Behav."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/s00702-015-1394-4","article-title":"Staging of cognitive deficits and neuropathological and ultrastructural changes in streptozotocin-induced rat model of Alzheimer\u2019s disease","volume":"122","author":"Knezovic","year":"2015","journal-title":"J. Neural Transm."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Spiers, J.G., Chen, H.J., Sernia, C., and Lavidis, N.A. (2015). Activation of the hypothalamic-pituitary-adrenal stress axis induces cellular oxidative stress. Front. Neurosci., 8.","DOI":"10.3389\/fnins.2014.00456"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Rocamora-Reverte, L., Villunger, A., and Wiegers, G.J. (2022). Cell-Specific Immune regulation by glucocorticoids in murine models of infection and inflammation. Cells, 11.","DOI":"10.3390\/cells11142126"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1159\/000362724","article-title":"One hormone, two actions: Anti- and pro-inflammatory effects of glucocorticoids","volume":"22","author":"Cidlowski","year":"2015","journal-title":"Neuroimmunomodulation"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6391686","DOI":"10.1155\/2016\/6391686","article-title":"Chronic stress and glucocorticoids: From neuronal plasticity to neurodegeneration","volume":"2016","author":"Vyas","year":"2016","journal-title":"Neural Plast."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Hu, P., Lu, Y., Pan, B.X., and Zhang, W.H. (2022). New insights into the pivotal role of the amygdala in inflammation-related depression and anxiety disorder. Int.J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911076"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s12979-024-00445-0","article-title":"Neuroinflammation in Alzheimer\u2019s disease: Insights from peripheral immune cells","volume":"21","author":"Zhang","year":"2024","journal-title":"Immun. Ageing"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41398-022-02297-y","article-title":"Neuroinflammation mechanisms of neuromodulation therapies for anxiety and depression","volume":"13","author":"Guo","year":"2023","journal-title":"Transl. Psychiatry"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Labandeira-Garcia, J.L., Costa-Besada, M.A., Labandeira, C.M., Villar-Cheda, B., and Rodr\u00edguez-Perez, A. (2017). Insulin-like growth factor-1 and neuroinflammation. Front. Aging Neurosci., 9.","DOI":"10.3389\/fnagi.2017.00365"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.4103\/1673-5374.272571","article-title":"Shifting equilibriums in Alzheimer\u2019s disease: The complex roles of microglia in neuroinflammation, neuronal survival and neurogenesis","volume":"15","author":"Gray","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1089\/neu.2017.5374","article-title":"Central infusion of insulin-like growth factor-1 increases hippocampal neurogenesis and improves neurobehavioral function after traumatic brain injury","volume":"35","author":"Carlson","year":"2018","journal-title":"J. Neurotrauma"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1054\/ghir.1999.0129","article-title":"Actions and interactions of the IGF system in Alzheimer\u2019s disease: Review and hypotheses","volume":"10","author":"Lackey","year":"2000","journal-title":"Growth Horm. IGF Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"442","DOI":"10.37349\/ent.2024.00093","article-title":"Potentialities of IGF-1 for regulating oxidative stress in neuroinflammation and neurodegeneration: Theoretical review","volume":"4","author":"Herrera","year":"2024","journal-title":"Explor. Neuroprot. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1016\/j.euroneuro.2014.07.002","article-title":"Prenatal stress affects insulin-like growth factor-1 (IGF-1) level and IGF-1 receptor phosphorylation in the brain of adult rats","volume":"24","author":"Szczesny","year":"2014","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Dunacka, J., Grembecka, B., Majkutewicz, I., and Wrona, D. (2025). Central insulin-like growth factor-1 treatment enhances working and reference memory by reducing neuroinflammation and amyloid beta deposition in a rat model of sporadic Alzheimer\u2019s disease. Pharmaceuticals, 18.","DOI":"10.3390\/ph18040527"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1212\/WNL.0000000000000382","article-title":"Insulin-like growth factor-1 and risk of Alzheimer dementia and brain atrophy","volume":"82","author":"Westwood","year":"2014","journal-title":"Neurology"},{"key":"ref_38","unstructured":"Paxinos, G., and Watson, C. (2007). The Rat Brain in Stereotaxic Coordinates, Academic Press. [6th ed.]."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2360","DOI":"10.1038\/sj.npp.1301358","article-title":"Increasing the levels of insulin-like growth factor-I by an IGF binding protein inhibitor produces anxiolytic and antidepressant-like effects","volume":"11","author":"Malberg","year":"2007","journal-title":"Neuropsychopharmacology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.psyneuen.2011.09.007","article-title":"Social deprivation stress is a triggering factor for the emergence of anxiety- and depression-like behaviours and leads to reduced brain BDNF levels in C57BL\/6J mice","volume":"37","author":"Berry","year":"2012","journal-title":"Psychoneuroendocrinology"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Fonseca-Rodrigues, D., Gon\u00e7alves, J., Laranjeira, I., Almeida, A., and Pinto-Ribeiro, F. (2022). Sucrose intake and preference by Wistar Han rats are not influenced by sex or food\/water deprivation. Pharmacol. Biochem. Behav., 216.","DOI":"10.1016\/j.pbb.2022.173387"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s11481-015-9632-y","article-title":"Medial septal NMDA glutamate Receptors are involved in modulation of blood natural killer cell activity in rats","volume":"11","author":"Podlacha","year":"2016","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"33","DOI":"10.2147\/JIR.S342280","article-title":"Dimethyl fumarate as the peripheral blood inflammatory mediators inhibitor in prevention of streptozotocin-induced neuroinflammation in aged rats","volume":"15","author":"Wrona","year":"2022","journal-title":"J. Inflamm. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jneuroim.2015.02.015","article-title":"Change in blood CD4+ T and CD8+ T lymphocytes in stressed rats pretreated chronically with desipramine are more pronounced after chronic open field stress challenge","volume":"282","author":"Listowska","year":"2015","journal-title":"J. Neuroimmunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA research framework: Toward a biological definition of Alzheimer\u2019s disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimers Dement."},{"key":"ref_46","doi-asserted-by":"crossref","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":"ref_47","doi-asserted-by":"crossref","first-page":"6113","DOI":"10.2147\/JIR.S385825","article-title":"Associations between neuropsychiatric symptoms and inflammation in neurodegenerative dementia: A systematic review","volume":"17","author":"Swann","year":"2024","journal-title":"J. Inflamm. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1038\/s41467-017-01150-x","article-title":"Earliest accumulation of \u03b2-amyloid occurs within the default-mode network and concurrently affects brain connectivity","volume":"8","author":"Palmqvist","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.mam.2015.05.005","article-title":"Neuropsychiatric symptoms in Alzheimer\u2019s disease: What might be associated brain circuits?","volume":"43\u201344","author":"Rosenberg","year":"2015","journal-title":"Mol. Asp. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1017\/S1041610213001725","article-title":"A review of neuroimaging findings of apathy in Alzheimer\u2019s disease","volume":"26","author":"Theleritis","year":"2014","journal-title":"Int. Psychogeriatr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/mp.2017.246","article-title":"Markers of microglia in post-mortem brain samples from patients with Alzheimer\u2019s disease: A systematic review","volume":"23","author":"Hopperton","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/s12974-016-0601-z","article-title":"Microglial immunophenotype in dementia with Alzheimer\u2019s pathology","volume":"13","author":"Minett","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"575","DOI":"10.30773\/pi.2019.06.07","article-title":"Anhedonia and dysphoria are differentially associated with the risk of dementia in the cognitively normal elderly individuals: A prospective cohort study","volume":"16","author":"Lee","year":"2019","journal-title":"Psychiatry Investig."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4107","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":"ref_55","doi-asserted-by":"crossref","unstructured":"Moreira-Silva, D., Carrettiero, D.C., Oliveira, A.S.A., Rodrigues, S., Dos Santos-Lopes, J., Canas, P.M., Cunha, R.A., Almeida, M.C., and Ferreira, T.L. (2018). Anandamide effects in a streptozotocin-induced Alzheimer\u2019s disease-like sporadic dementia in rats. Front. Neurosci., 12.","DOI":"10.3389\/fnins.2018.00653"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1007\/s12640-022-00563-x","article-title":"Cognitive dysfunction and anxiety resulting from synaptic downscaling, hippocampal atrophy, and ventricular enlargement with intracerebroventricular streptozotocin injection in male Wistar rats","volume":"40","author":"Roy","year":"2022","journal-title":"Neurotox. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3463","DOI":"10.1073\/pnas.1500877112","article-title":"Insulin resistance in brain alters dopamine turnover and causes behavioral disorders","volume":"112","author":"Kleinridders","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e67267","DOI":"10.7554\/eLife.67267","article-title":"IGF-1 facilitates extinction of conditioned fear","volume":"10","author":"Maglio","year":"2021","journal-title":"eLife"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Bake, S., Selvamani, A., Cherry, J., and Sohrabji, F. (2014). Blood brain barrier and neuroinflammation are critical targets of IGF-1-mediated neuroprotection in stroke for middle-aged female rats. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091427"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"265","DOI":"10.14283\/jpad.2020.11","article-title":"The interrelationship between insulin-like growth factor 1, apolipoprotein E \u03b54, lifestyle factors, and the aging body and brain","volume":"7","author":"Galle","year":"2020","journal-title":"J. Prev. Alzheimers Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/BF01922416","article-title":"Evidence for suppression of immune function by insulin-like growth factor-1 in dwarf rats in vivo","volume":"52","author":"Schurmann","year":"1996","journal-title":"Experientia"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"19","DOI":"10.4142\/jvs.2014.15.1.19","article-title":"Sequential alterations of glucocorticoid receptors in the hippocampus of STZ-treated type 1 diabetic rats","volume":"15","author":"Shin","year":"2014","journal-title":"J. Vet. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/nrendo.2015.168","article-title":"Hormonal control of T-cell development in health and disease","volume":"12","author":"Savino","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.1182\/blood-2008-04-149435","article-title":"Exogenous insulin-like growth factor 1 enhances thymopoiesis predominantly through thymic epithelial cell expansion","volume":"112","author":"Chu","year":"2008","journal-title":"Blood"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.bbi.2020.05.070","article-title":"CD8+ T-cells infiltrate Alzheimer\u2019s disease brains and regulate neuronal- and synapse-related gene expression in APP-PS1 transgenic mice","volume":"89","author":"Unger","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1210\/en.2015-1840","article-title":"Insulin-like growth factor (IGF)-I modulates endothelial blood-brain barrier function in ischemic middle-aged female rats","volume":"157","author":"Bake","year":"2016","journal-title":"Endocrinology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.expneurol.2018.09.016","article-title":"Insulin-like Growth Factor (IGF)-1 treatment stabilizes the microvascular cytoskeleton under ischemic conditions","volume":"311","author":"Bake","year":"2019","journal-title":"Exp. Neurol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.bbi.2024.08.008","article-title":"Peripheral, but not central, IGF-1 treatment attenuates stroke-induced cognitive impairment in middle-aged female Sprague Dawley rats: The gut as a therapeutic target","volume":"122","author":"Mani","year":"2024","journal-title":"Brain Behav. Immun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1172\/JCI116621","article-title":"Insulin-like growth factor-1 stimulation of lymphopoiesis","volume":"92","author":"Clark","year":"1993","journal-title":"J. Clin. Investig."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.15252\/emmm.201303376","article-title":"Insulin-like growth factor-1 stimulates regulatory T cells and suppresses autoimmune disease","volume":"6","author":"Bilbao","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.kjms.2018.02.004","article-title":"IGF-1 defends against chronic-stress induced depression in rat models of chronic unpredictable mild stress through the PI3K\/Akt\/FoxO3a pathway","volume":"34","author":"Kuang","year":"2018","journal-title":"Kaohsiung J. Med. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"107300","DOI":"10.1016\/j.phrs.2024.107300","article-title":"PI3K\/AKT signaling pathway: Molecular mechanisms and therapeutic potential in depression","volume":"206","author":"Guo","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Arjunan, A., Sah, D.K., Woo, M., and Song, J. (2023). Identification of the molecular mechanism of insulin-like growth factor-1 (IGF-1): A promising therapeutic target for neurodegenerative diseases associated with metabolic syndrome. 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