{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:00:50Z","timestamp":1791900050335,"version":"4.3.4"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100012001","name":"Al Jalila Foundation","doi-asserted-by":"crossref","award":["AJF2018082"],"award-info":[{"award-number":["AJF2018082"]}],"id":[{"id":"10.13039\/100012001","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","award":["UOS-BI2017"],"award-info":[{"award-number":["UOS-BI2017"]}],"id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1007\/s12035-025-05378-3","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T08:25:14Z","timestamp":1764923114000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Brain-Derived Neurotrophic Factor and Heat Shock Protein-32: Potential Targets for Microglial Response to Glucose and Oxygen Manipulation"],"prefix":"10.1007","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1554-6319","authenticated-orcid":false,"given":"Bashair M.","family":"Mussa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankita","family":"Srivastava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khuloud","family":"Bajbouj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Shafarin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reeja","family":"Rajan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa","family":"Hisham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"5378_CR1","unstructured":"International Diabetes Federation (2025) IDF Diabetes Atlas 2025, pages 41 and 83. Retrieved from\nhttps:\/\/diabetesatlas.org\/resources\/idf-diabetes-atlas-2025\/"},{"key":"5378_CR2","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1007\/s40265-015-0347-4","volume":"75","author":"K Semenkovich","year":"2015","unstructured":"Semenkovich K, Brown ME, Svrakic DM, Lustman PJ (2015) Depression in type 2 diabetes mellitus: prevalence, impact, and treatment. Drugs 75:577\u2013587","journal-title":"Drugs"},{"issue":"3","key":"5378_CR3","doi-asserted-by":"publisher","DOI":"10.4082\/kjfm.2018.39.3.137","volume":"39","author":"A Alzoubi","year":"2018","unstructured":"Alzoubi A, Abunaser R, Khassawneh A, Alfaqih M, Khasawneh A, Abdo N (2018) The bidirectional relationship between diabetes and depression: a literature review. Korean J Fam Med 39(3):137","journal-title":"Korean J Fam Med"},{"issue":"6","key":"5378_CR4","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.5114\/aoms.2015.56342","volume":"11","author":"S Bathina","year":"2015","unstructured":"Bathina S, Das UN (2015) Brain-derived neurotrophic factor and its clinical implications. Arch Med Sci 11(6):1164\u20131178","journal-title":"Arch Med Sci"},{"key":"5378_CR5","doi-asserted-by":"publisher","first-page":"101016","DOI":"10.1016\/j.cegh.2022.101016","volume":"15","author":"R Parveen","year":"2022","unstructured":"Parveen R, Kapur P, Kohli S, Agarwal NB (2022) Attenuated brain derived neurotrophic factor and depression in type 2 diabetes mellitus patients: a case-control study. Clin Epidemiol Glob Health 15:101016","journal-title":"Clin Epidemiol Glob Health"},{"issue":"1","key":"5378_CR6","first-page":"978143","volume":"2014","author":"B Boyuk","year":"2014","unstructured":"Boyuk B, Degirmencioglu S, Atalay H, Guzel S, Acar A, Celebi A, Ekizoglu I, Simsek C (2014) Relationship between levels of brain-derived neurotrophic factor and metabolic parameters in patients with type 2 diabetes mellitus. J Diabetes Res 2014(1):978143","journal-title":"J Diabetes Res"},{"issue":"1","key":"5378_CR7","first-page":"6871089","volume":"2017","author":"W Liu","year":"2017","unstructured":"Liu W, Ge T, Leng Y, Pan Z, Fan J, Yang W, Cui R (2017) The role of neural plasticity in depression: from hippocampus to prefrontal cortex. Neural Plast 2017(1):6871089","journal-title":"Neural Plast"},{"key":"5378_CR8","doi-asserted-by":"publisher","first-page":"430","DOI":"10.3389\/fncel.2014.00430","volume":"8","author":"F Calabrese","year":"2014","unstructured":"Calabrese F, Rossetti AC, Racagni G, Gass P, Riva MA, Molteni R (2014) Brain-derived neurotrophic factor: a bridge between inflammation and neuroplasticity. Front Cell Neurosci 8:430","journal-title":"Front Cell Neurosci"},{"issue":"20","key":"5378_CR9","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21207777","volume":"21","author":"L Colucci-D\u2019Amato","year":"2020","unstructured":"Colucci-D\u2019Amato L, Speranza L, Volpicelli F (2020) Neurotrophic factor BDNF, physiological functions and therapeutic potential in depression, neurodegeneration and brain cancer. Int J Mol Sci 21(20):7777","journal-title":"Int J Mol Sci"},{"issue":"1","key":"5378_CR10","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1038\/s41598-018-37215-0","volume":"9","author":"CF Hsieh","year":"2019","unstructured":"Hsieh CF, Liu CK, Lee CT, Yu LE, Wang JY (2019) Acute glucose fluctuation impacts microglial activity, leading to inflammatory activation or self-degradation. Sci Rep 9(1):840","journal-title":"Sci Rep"},{"key":"5378_CR11","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.jad.2023.09.017","volume":"343","author":"M Kwon","year":"2023","unstructured":"Kwon M, Lee M, Kim EH, Choi DW, Jung E, Kim KY, Jung I, Ha J (2023) Risk of depression and anxiety disorders according to long-term glycemic variability. J Affect Disord 343:50\u201358","journal-title":"J Affect Disord"},{"key":"5378_CR12","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1007\/s12975-013-0271-4","volume":"4","author":"FR Sharp","year":"2013","unstructured":"Sharp FR, Zhan X, Liu DZ (2013) Heat shock proteins in the brain: role of Hsp70, Hsp 27, and HO-1 (Hsp32) and their therapeutic potential. Transl Stroke Res 4:685\u2013692","journal-title":"Transl Stroke Res"},{"issue":"1","key":"5378_CR13","first-page":"92","volume":"43","author":"SD Nikukheslat","year":"2021","unstructured":"Nikukheslat SD, Karimi P, Sadri I (2021) Effect of aerobic training on heat shock protein 27 and brain-derived neurotrophic factor in hippocampus and prefrontal cortex of type II diabetic rats. Med J Tabriz Univ Med Sci Health Serv 43(1):92\u201399","journal-title":"Med J Tabriz Univ Med Sci Health Serv"},{"key":"5378_CR14","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1007\/s004010000202","volume":"100","author":"R Beschorner","year":"2000","unstructured":"Beschorner R, Adjodah D, Schwab JM, Mittelbronn M, Pedal I, Mattern R, Schluesener HJ, Meyermann R (2000) Long-term expression of heme oxygenase-1 (HO-1, HSP-32) following focal cerebral infarctions and traumatic brain injury in humans. Acta Neuropathol 100:377\u2013384","journal-title":"Acta Neuropathol"},{"issue":"6","key":"5378_CR15","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1161\/STROKEAHA.110.596718","volume":"42","author":"J Aronowski","year":"2011","unstructured":"Aronowski J, Zhao X (2011) Molecular pathophysiology of cerebral hemorrhage: secondary brain injury. Stroke 42(6):1781\u20131786","journal-title":"Stroke"},{"key":"5378_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s42826-019-0020-2","volume":"35","author":"HJ Kwon","year":"2019","unstructured":"Kwon HJ, Kim W, Jung HY, Kang MS, Kim JW, Hahn KR, Yoo DY, Yoon YS, Hwang IK, Kim DW (2019) Heat shock protein 70 increases cell proliferation, neuroblast differentiation, and the phosphorylation of CREB in the hippocampus. Laboratory animal research 35:1\u201311","journal-title":"Laboratory animal research"},{"key":"5378_CR17","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/s11010-019-03612-w","volume":"462","author":"X Sun","year":"2019","unstructured":"Sun X, Yin Y, Kong L, Chen W, Miao C, Chen J (2019) The effect of propofol on hypoxia-modulated expression of heat shock proteins: potential mechanism in modulating blood\u2013brain barrier permeability. Mol Cell Biochem 462:85\u201396","journal-title":"Mol Cell Biochem"},{"key":"5378_CR18","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2023.1131683","volume":"17","author":"IF Belenichev","year":"2023","unstructured":"Belenichev IF, Aliyeva OG, Popazova OO, Bukhtiyarova NV (2023) Involvement of heat shock proteins HSP70 in the mechanisms of endogenous neuroprotection: the prospect of using HSP70 modulators. Front Cell Neurosci 17:1131683","journal-title":"Front Cell Neurosci"},{"issue":"1\u20132","key":"5378_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.brainres.2003.11.064","volume":"1002","author":"PC Guest","year":"2004","unstructured":"Guest PC, Knowles MR, Molon-Noblot S, Salim K, Smith D, Murray F, Laroque P, Hunt SP, De Felipe C, Rupniak NM, McAllister G (2004) Mechanisms of action of the antidepressants fluoxetine and the substance P antagonist L-000760735 are associated with altered neurofilaments and synaptic remodeling. Brain Res 1002(1\u20132):1\u201310","journal-title":"Brain Res"},{"issue":"9","key":"5378_CR20","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1139\/cjpp-2019-0679","volume":"98","author":"Y Abdul","year":"2020","unstructured":"Abdul Y, Jamil S, He L, Li W, Ergul A (2020) Endothelin-1 (ET-1) promotes a proinflammatory microglia phenotype in diabetic conditions. Can J Physiol Pharmacol 98(9):596\u2013603","journal-title":"Can J Physiol Pharmacol"},{"key":"5378_CR21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2025.119467","author":"H Xu","year":"2025","unstructured":"Xu H, Chen Q (2025) The bidirectional influence between type 2 diabetes mellitus and the state of depression and anxiety. J Affect Disord. https:\/\/doi.org\/10.1016\/j.jad.2025.119467","journal-title":"J Affect Disord"},{"key":"5378_CR22","doi-asserted-by":"publisher","unstructured":"Colonna M, Butovsky O (2017) Microglia function in the central nervous system during health and neurodegeneration. Annu Rev Immunol 35:441\u2013468.  https:\/\/doi.org\/10.1146\/annurev-immunol-051116-052358.  Annual Reviews Inc","DOI":"10.1146\/annurev-immunol-051116-052358"},{"issue":"13","key":"5378_CR23","doi-asserted-by":"publisher","first-page":"4124","DOI":"10.3390\/molecules27134124","volume":"27","author":"ZM Althafar","year":"2022","unstructured":"Althafar ZM (2022) Targeting microglia in Alzheimer\u2019s disease: from molecular mechanisms to potential therapeutic targets for small molecules. Molecules 27(13):4124","journal-title":"Molecules"},{"key":"5378_CR24","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111703","volume":"140","author":"O Qiao","year":"2021","unstructured":"Qiao O, Ji H, Zhang Y, Zhang X, Zhang X, Liu N, Huang L, Liu C, Gao W (2021) New insights in drug development for Alzheimer\u2019s disease based on microglia function. Biomed Pharmacother 140:111703","journal-title":"Biomed Pharmacother"},{"issue":"1","key":"5378_CR25","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1186\/s12974-022-02492-0","volume":"19","author":"H Wang","year":"2022","unstructured":"Wang H, He Y, Sun Z, Ren S, Liu M, Wang G, Yang J (2022) Microglia in depression: an overview of microglia in the pathogenesis and treatment of depression. J Neuroinflammation 19(1):132","journal-title":"J Neuroinflammation"},{"issue":"11","key":"5378_CR26","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.3390\/cells12111521","volume":"12","author":"R Afridi","year":"2023","unstructured":"Afridi R, Suk K (2023) Microglial responses to stress-induced depression: causes and consequences. Cells 12(11):1521","journal-title":"Cells"},{"key":"5378_CR27","doi-asserted-by":"publisher","first-page":"874258","DOI":"10.3389\/fncel.2022.874258","volume":"16","author":"C Dedert","year":"2022","unstructured":"Dedert C, Mishra V, Aggarwal G, Nguyen AD, Xu F (2022) Progranulin preserves autophagy flux and mitochondrial function in rat cortical neurons under high glucose stress. Front Cell Neurosci 16:874258","journal-title":"Front Cell Neurosci"},{"issue":"4","key":"5378_CR28","doi-asserted-by":"publisher","first-page":"674","DOI":"10.14336\/AD.2017.1208","volume":"9","author":"W Li","year":"2018","unstructured":"Li W, Choudhury GR, Winters A, Prah J, Lin W, Liu R, Yang SH (2018) Hyperglycemia alters astrocyte metabolism and inhibits astrocyte proliferation. Aging Dis 9(4):674","journal-title":"Aging Dis"},{"issue":"1","key":"5378_CR29","first-page":"294","volume":"43","author":"Y Zhong","year":"2019","unstructured":"Zhong Y, Zhu Y, He T, Li W, Li Q, Miao Y (2019) Brain-derived neurotrophic factor inhibits hyperglycemia-induced apoptosis and downregulation of synaptic plasticity-related proteins in hippocampal neurons via the PI3K\/Akt pathway. Int J Mol Med 43(1):294\u2013304","journal-title":"Int J Mol Med"},{"key":"5378_CR30","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3389\/fnmol.2011.00005","volume":"4","author":"K Zhang","year":"2011","unstructured":"Zhang K, Zhu L, Fan M (2011) Oxygen, a key factor regulating cell behavior during neurogenesis and cerebral diseases. Front Mol Neurosci 4:5","journal-title":"Front Mol Neurosci"},{"issue":"3","key":"5378_CR31","first-page":"375","volume":"40","author":"K Krnjevi\u00e6","year":"1999","unstructured":"Krnjevi\u00e6 K (1999) Early effects of hypoxia on brain cell function. Croat Med J 40(3):375\u2013380","journal-title":"Croat Med J"},{"issue":"7","key":"5378_CR32","doi-asserted-by":"publisher","first-page":"e0129489","DOI":"10.1371\/journal.pone.0129489","volume":"10","author":"W Hartman","year":"2015","unstructured":"Hartman W, Helan M, Smelter D, Sathish V, Thompson M, Pabelick CM, Johnson B, Prakash YS (2015) Role of hypoxia-induced brain derived neurotrophic factor in human pulmonary artery smooth muscle. PLoS ONE 10(7):e0129489","journal-title":"PLoS ONE"},{"issue":"7","key":"5378_CR33","doi-asserted-by":"publisher","DOI":"10.3390\/membranes11070470","volume":"11","author":"M Morishima","year":"2021","unstructured":"Morishima M, Fujita T, Osagawa S, Kubota H, Ono K (2021) Enhanced BDNF actions following acute hypoxia facilitate HIF-1\u03b1-dependent upregulation of Cav3-T-type Ca2+ channels in rat cardiomyocytes. Membranes 11(7):470","journal-title":"Membranes"},{"issue":"6","key":"5378_CR34","doi-asserted-by":"publisher","first-page":"3651","DOI":"10.1074\/jbc.M109.068577","volume":"285","author":"W Luo","year":"2010","unstructured":"Luo W, Zhong J, Chang R, Hu H, Pandey A, Semenza GL (2010) Hsp70 and CHIP selectively mediate ubiquitination and degradation of hypoxia-inducible factor (HIF)-1\u03b1 but not HIF-2\u03b1. J Biol Chem 285(6):3651\u20133663. https:\/\/doi.org\/10.1074\/jbc.M109.068577","journal-title":"J Biol Chem"},{"issue":"8","key":"5378_CR35","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1002\/jor.22623","volume":"32","author":"S Tsuchida","year":"2014","unstructured":"Tsuchida S, Arai Y, Takahashi KA, Kishida T, Terauchi R, Honjo K, Nakagawa S, Inoue H et al (2014) HIF-1\u03b1-induced HSP70 regulates anabolic responses in articular chondrocytes under hypoxic conditions. J Orthop Res 32(8):975\u2013980. https:\/\/doi.org\/10.1002\/jor.22623","journal-title":"J Orthop Res"},{"issue":"6","key":"5378_CR36","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.5114\/aoms.2014.45089","volume":"10","author":"A Nowak","year":"2014","unstructured":"Nowak A, Szaflik JP, Gacek M, Przybylowska-Sygut K, Kami\u0144ska A, Szaflik J, Majsterek I (2014) BDNF and HSP gene polymorphisms and their influence on the progression of primary open-angle glaucoma in a Polish population. Arch Med Sci 10(6):1206\u20131213. https:\/\/doi.org\/10.5114\/aoms.2014.45089","journal-title":"Arch Med Sci"},{"key":"5378_CR37","doi-asserted-by":"publisher","first-page":"4249","DOI":"10.1158\/0008-5472.CAN-05-2789","volume":"66","author":"K Nakamura","year":"2006","unstructured":"Nakamura K, Martin KC, Jackson JK, Beppu K, Woo CW, Thiele CJ (2006) Brain-derived neurotrophic factor activation of TrkB induces vascular endothelial growth factor expression via hypoxia-inducible factor-1alpha in neuroblastoma cells. Cancer Res 66:4249\u20134255. https:\/\/doi.org\/10.1158\/0008-5472.CAN-05-2789","journal-title":"Cancer Res"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-025-05378-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-025-05378-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-025-05378-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T08:25:17Z","timestamp":1764923117000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-025-05378-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,5]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["5378"],"URL":"https:\/\/doi.org\/10.1007\/s12035-025-05378-3","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,5]]},"assertion":[{"value":"10 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"252"}}