{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T05:19:24Z","timestamp":1792214364068,"version":"4.4.0"},"reference-count":79,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T00:00:00Z","timestamp":1672272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T00:00:00Z","timestamp":1672272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81901370"],"award-info":[{"award-number":["81901370"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82001328"],"award-info":[{"award-number":["82001328"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"crossref","award":["2019M653665"],"award-info":[{"award-number":["2019M653665"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100020209","name":"Shaanxi Provincial Health Commission","doi-asserted-by":"publisher","award":["2022D012"],"award-info":[{"award-number":["2022D012"]}],"id":[{"id":"10.13039\/501100020209","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neuroinflammation in the nucleus accumbens (NAc) is well known to influence the progression of depression. However, the molecular mechanisms triggering NAc neuroinflammation in depression have not been fully elucidated. Progranulin (PGRN) is a multifunctional growth factor that is linked to the innate immune response and inflammation, and PGRN plays a key role in neurodegenerative diseases such as frontotemporal dementia (FTD). Here, the purpose of this study was to validate whether PGRN was involved in the NAc neuroinflammation-promoted depressive-like phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A NAc neuroinflammation-relevant depression-like model was established using wild-type (WT) and PGRN-knockout (KO) mice after NAc injection with lipopolysaccharide (LPS), and various behavioral tests related to cognition, social recognition, depression and anxiety were performed with WT and PGRNKO mice with or without NAc immune challenge. RT\u2012PCR, ELISA, western blotting and immunofluorescence staining were used to determine the expression and function of PGRN in the neuroinflammatory reaction in the NAc after LPS challenge. The morphology of neurons in the NAc from WT and PGRNKO mice under conditions of NAc neuroinflammation was analyzed using Golgi\u2013Cox staining, followed by Sholl analyses. The potential signaling pathways involved in NAc neuroinflammation in PGRNKO mice were investigated by western blotting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Under normal conditions, PGRN deficiency induced FTD-like behaviors in mice and astrocyte activation in the NAc, promoted the release of the inflammatory cytokines interleukin (IL)-6 and IL-10 and increased dendritic complexity and synaptic protein BDNF levels in the NAc. However, NAc neuroinflammation enhanced PGRN expression, which was located in astrocytes and microglia within the NAc, and PGRN deficiency in mice alleviated NAc neuroinflammation-elicited depression-like behaviors, seemingly inhibiting astrocyte- and microglia-related inflammatory reactions and neuroplasticity complexity in the NAc via the p38 and nuclear factor of kappa (NF-\u03baB) signaling pathways present in the NAc after neuroinflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results suggest that PGRN exerts distinct function on different behaviors, showing protective roles in the FTD-like behavior and detrimental effects on the neuroinflammation-related depression-like behavior, resulting from mediating astrocyte and microglial functions from the NAc in different status.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12974-022-02684-8","type":"journal-article","created":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T08:08:16Z","timestamp":1672301296000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Progranulin from different gliocytes in the nucleus accumbens exerts distinct roles in FTD- and neuroinflammation-induced depression-like behaviors"],"prefix":"10.1186","volume":"19","author":[{"given":"Jing","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simin","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihao","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weina","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqi","family":"Sha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjiong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,12,29]]},"reference":[{"issue":"10161","key":"2684_CR1","doi-asserted-by":"publisher","first-page":"2299","DOI":"10.1016\/S0140-6736(18)31948-2","volume":"392","author":"GS Malhi","year":"2018","unstructured":"Malhi GS, Mann JJ. Depression. Lancet. 2018;392(10161):2299\u2013312.","journal-title":"Lancet"},{"key":"2684_CR2","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1080\/08870446.2020.1782410","volume":"36","author":"F Tang","year":"2021","unstructured":"Tang F, Liang J, Zhang H, Kelifa MM, He Q, Wang P. COVID-19 related depression and anxiety among quarantined respondents. Psychol Health. 2021;36:164\u201378.","journal-title":"Psychol Health"},{"key":"2684_CR3","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1038\/nrn3381","volume":"14","author":"SJ Russo","year":"2013","unstructured":"Russo SJ, Nestler EJ. The brain reward circuitry in mood disorders. Nat Rev Neurosci. 2013;14:609\u201325.","journal-title":"Nat Rev Neurosci"},{"key":"2684_CR4","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1007\/s40473-015-0044-3","volume":"2","author":"M Heshmati","year":"2015","unstructured":"Heshmati M, Russo SJ. Anhedonia and the brain reward circuitry in depression. Curr Behav Neurosci Rep. 2015;2:146\u201353.","journal-title":"Curr Behav Neurosci Rep"},{"key":"2684_CR5","doi-asserted-by":"publisher","first-page":"2258","DOI":"10.1038\/npp.2015.75","volume":"40","author":"TD Satterthwaite","year":"2015","unstructured":"Satterthwaite TD, Kable JW, Vandekar L, Katchmar N, Bassett DS, Baldassano CF, et al. Common and dissociable dysfunction of the reward system in bipolar and unipolar depression. Neuropsychopharmacology. 2015;40:2258\u201368.","journal-title":"Neuropsychopharmacology"},{"key":"2684_CR6","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1176\/appi.ajp.2008.08081201","volume":"166","author":"DA Pizzagalli","year":"2009","unstructured":"Pizzagalli DA, Holmes AJ, Dillon DG, Goetz EL, Birk JL, Bogdan R, et al. Reduced caudate and nucleus accumbens response to rewards in unmedicated individuals with major depressive disorder. Am J Psychiatry. 2009;166:702\u201310.","journal-title":"Am J Psychiatry"},{"key":"2684_CR7","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1016\/j.biopsych.2015.08.009","volume":"79","author":"C Anacker","year":"2016","unstructured":"Anacker C, Scholz J, O\u2019Donnell KJ, Allemang-Grand R, Diorio J, Bagot RC, et al. Neuroanatomic differences associated with stress susceptibility and resilience. Biol Psychiatry. 2016;79:840\u20139.","journal-title":"Biol Psychiatry"},{"key":"2684_CR8","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1038\/sj.npp.1301408","volume":"33","author":"TE Schlaepfer","year":"2008","unstructured":"Schlaepfer TE, Cohen MX, Frick C, Kosel M, Brodesser D, Axmacher N, et al. Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression. Neuropsychopharmacology. 2008;33:368\u201377.","journal-title":"Neuropsychopharmacology"},{"key":"2684_CR9","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.biopsych.2009.09.013","volume":"67","author":"BH Bewernick","year":"2010","unstructured":"Bewernick BH, Hurlemann R, Matusch A, Kayser S, Grubert C, Hadrysiewicz B, et al. Nucleus accumbens deep brain stimulation decreases ratings of depression and anxiety in treatment-resistant depression. Biol Psychiatry. 2010;67:110\u20136.","journal-title":"Biol Psychiatry"},{"key":"2684_CR10","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.biopsych.2016.09.007","volume":"81","author":"TC Francis","year":"2017","unstructured":"Francis TC, Lobo MK. Emerging role for nucleus accumbens medium spiny neuron subtypes in depression. Biol Psychiatry. 2017;81:645\u201353.","journal-title":"Biol Psychiatry"},{"key":"2684_CR11","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.biopsych.2014.07.021","volume":"77","author":"TC Francis","year":"2015","unstructured":"Francis TC, Chandra R, Friend DM, Finkel E, Dayrit G, Miranda J, et al. Nucleus accumbens medium spiny neuron subtypes mediate depression-related outcomes to social defeat stress. Biol Psychiatry. 2015;77:212\u201322.","journal-title":"Biol Psychiatry"},{"key":"2684_CR12","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/j.biopsych.2009.03.015","volume":"66","author":"NA Harrison","year":"2009","unstructured":"Harrison NA, Brydon L, Walker C, Gray MA, Steptoe A, Critchley HD. Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biol Psychiatry. 2009;66:407\u201314.","journal-title":"Biol Psychiatry"},{"key":"2684_CR13","doi-asserted-by":"publisher","first-page":"1752","DOI":"10.1038\/s41593-017-0010-3","volume":"20","author":"C Menard","year":"2017","unstructured":"Menard C, Pfau ML, Hodes GE, Kana V, Wang VX, Bouchard S, et al. Social stress induces neurovascular pathology promoting depression. Nat Neurosci. 2017;20:1752\u201360.","journal-title":"Nat Neurosci"},{"key":"2684_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.molmet.2018.01.018","volume":"10","author":"L D\u00e9carie-Spain","year":"2018","unstructured":"D\u00e9carie-Spain L, Sharma S, Hryhorczuk C, Issa-Garcia V, Barker PA, Arbour N, et al. Nucleus accumbens inflammation mediates anxiodepressive behavior and compulsive sucrose seeking elicited by saturated dietary fat. Mol Metab. 2018;10:1\u201313.","journal-title":"Mol Metab"},{"key":"2684_CR15","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1093\/ijnp\/pyy005","volume":"21","author":"J Wang","year":"2018","unstructured":"Wang J, Jia Y, Li G, Wang B, Zhou T, Zhu L, et al. The Dopamine receptor D3 regulates lipopolysaccharide-induced depressive-like behavior in mice. Int J Neuropsychopharmacol. 2018;21:448\u201360.","journal-title":"Int J Neuropsychopharmacol"},{"key":"2684_CR16","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.bbi.2021.12.019","volume":"101","author":"J Wang","year":"2022","unstructured":"Wang J, Lai S, Wang R, Zhou T, Dong N, Zhu L, et al. Dopamine D3 receptor in the nucleus accumbens alleviates neuroinflammation in a mouse model of depressive-like behavior. Brain Behav Immun. 2022;101:165\u201379.","journal-title":"Brain Behav Immun"},{"key":"2684_CR17","first-page":"5590","volume":"62","author":"Z He","year":"2002","unstructured":"He Z, Ismail A, Kriazhev L, Sadvakassova G, Bateman A. Progranulin (PC-cell-derived growth factor\/acrogranin) regulates invasion and cell survival. Cancer Res. 2002;62:5590\u20136.","journal-title":"Cancer Res"},{"key":"2684_CR18","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1038\/nm816","volume":"9","author":"Z He","year":"2003","unstructured":"He Z, Ong CH, Halper J, Bateman A. Progranulin is a mediator of the wound response. Nat Med. 2003;9:225\u20139.","journal-title":"Nat Med"},{"key":"2684_CR19","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1126\/science.1199214","volume":"332","author":"W Tang","year":"2011","unstructured":"Tang W, Lu Y, Tian QY, Zhang Y, Guo FJ, Liu GY, et al. The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science. 2011;332:478\u201384.","journal-title":"Science"},{"key":"2684_CR20","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1007\/s00296-015-3372-4","volume":"36","author":"J Chen","year":"2016","unstructured":"Chen J, Li S, Shi J, Zhang L, Li J, Chen S, et al. Serum progranulin irrelated with Breg cell levels, but elevated in RA patients, reflecting high disease activity. Rheumatol Int. 2016;36:359\u201364.","journal-title":"Rheumatol Int"},{"key":"2684_CR21","doi-asserted-by":"publisher","first-page":"1733","DOI":"10.1007\/s10620-014-3089-3","volume":"59","author":"L Thurner","year":"2014","unstructured":"Thurner L, St\u00f6ger E, Fadle N, Klemm P, Regitz E, Kemele M, et al. Proinflammatory progranulin antibodies in inflammatory bowel diseases. Dig Dis Sci. 2014;59:1733\u201342.","journal-title":"Dig Dis Sci"},{"key":"2684_CR22","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1111\/imm.12446","volume":"145","author":"K Huang","year":"2015","unstructured":"Huang K, Chen A, Zhang X, Song Z, Xu H, Cao J, et al. Progranulin is preferentially expressed in patients with psoriasis vulgaris and protects mice from psoriasis-like skin inflammation. Immunology. 2015;145:279\u201387.","journal-title":"Immunology"},{"key":"2684_CR23","first-page":"97","volume":"44","author":"M Pogonowska","year":"2019","unstructured":"Pogonowska M, Poniatowski \u0141A, Wawrzyniak A, Kr\u00f3likowska K, Kalicki B. The role of progranulin (PGRN) in the modulation of anti-inflammatory response in asthma. Cent Eur J Immunol. 2019;44:97\u2013101.","journal-title":"Cent Eur J Immunol"},{"key":"2684_CR24","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.2741\/4274","volume":"19","author":"Q Tian","year":"2014","unstructured":"Tian Q, Zhao Y, Mundra JJ, Gonzalez-Gugel E, Jian J, Uddin SM, et al. Three TNFR-binding domains of PGRN act independently in inhibition of TNF-alpha binding and activity. Front Biosci. 2014;19:1176\u201385.","journal-title":"Front Biosci"},{"key":"2684_CR25","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1007\/978-1-4939-0669-7_14","volume":"1155","author":"Q Tian","year":"2014","unstructured":"Tian Q, Zhao S, Liu C. A solid-phase assay for studying direct binding of progranulin to TNFR and progranulin antagonism of TNF\/TNFR interactions. Methods Mol Biol. 2014;1155:163\u201372.","journal-title":"Methods Mol Biol"},{"key":"2684_CR26","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.yexcr.2018.04.001","volume":"367","author":"L Li","year":"2018","unstructured":"Li L, Li L, Xiao L, Shangguan J. Progranulin ameliorates coxsackievirus-B3-induced viral myocarditis by downregulating Th1 and Th17 cells. Exp Cell Res. 2018;367:241\u201350.","journal-title":"Exp Cell Res"},{"key":"2684_CR27","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1096\/fj.201601134R","volume":"31","author":"W Fu","year":"2017","unstructured":"Fu W, Hu W, Shi L, Mundra JJ, Xiao G, Dustin ML, et al. Foxo4- and Stat3-dependent IL-10 production by progranulin in regulatory T cells restrains inflammatory arthritis. FASEB J. 2017;31:1354\u201367.","journal-title":"FASEB J"},{"key":"2684_CR28","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1038\/35047123","volume":"408","author":"H Hemmi","year":"2000","unstructured":"Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, et al. A toll-like receptor recognizes bacterial DNA. Nature. 2000;408:740\u20135.","journal-title":"Nature"},{"key":"2684_CR29","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1146\/annurev.immunol.20.100301.064842","volume":"20","author":"AM Krieg","year":"2002","unstructured":"Krieg AM. CpG motifs in bacterial DNA and their immune effects. Annu Rev Immunol. 2002;20:709\u201360.","journal-title":"Annu Rev Immunol"},{"key":"2684_CR30","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1016\/S0092-8674(02)01141-8","volume":"111","author":"J Zhu","year":"2002","unstructured":"Zhu J, Nathan C, Jin W, Sim D, Ashcroft GS, Wahl SM, et al. Conversion of proepithelin to epithelins: roles of SLPI and elastase in host defense and wound repair. Cell. 2002;111:867\u201378.","journal-title":"Cell"},{"key":"2684_CR31","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1177\/1352458511406164","volume":"17","author":"M Vercellino","year":"2011","unstructured":"Vercellino M, Grifoni S, Romagnolo A, Masera S, Mattioda A, Trebini C, et al. Progranulin expression in brain tissue and cerebrospinal fluid levels in multiple sclerosis. Mult Scler. 2011;17:1194\u2013201.","journal-title":"Mult Scler"},{"key":"2684_CR32","doi-asserted-by":"publisher","first-page":"3931","DOI":"10.1002\/cne.22430","volume":"518","author":"TL Petkau","year":"2010","unstructured":"Petkau TL, Neal SJ, Orban PC, MacDonald JL, Hill AM, Lu G, et al. Progranulin expression in the developing and adult murine brain. J Comp Neurol. 2010;518:3931\u201347.","journal-title":"J Comp Neurol"},{"key":"2684_CR33","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s13024-021-00513-9","volume":"17","author":"T Zhang","year":"2022","unstructured":"Zhang T, Du H, Santos MN, Wu X, Pagan MD, Trigiani LJ, et al. Differential regulation of progranulin derived granulin peptides. Mol Neurodegener. 2022;17:15.","journal-title":"Mol Neurodegener"},{"key":"2684_CR34","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/j.tips.2021.11.015","volume":"43","author":"H Rhinn","year":"2022","unstructured":"Rhinn H, Tatton N, McCaughey S, Kurnellas M, Rosenthal A. Progranulin as a therapeutic target in neurodegenerative diseases. Trends Pharmacol Sci. 2022;43:641\u201352.","journal-title":"Trends Pharmacol Sci"},{"key":"2684_CR35","doi-asserted-by":"publisher","first-page":"81","DOI":"10.5114\/fn.2021.105137","volume":"59","author":"M Olczak","year":"2021","unstructured":"Olczak M, Poniatowski \u0141A, Siwi\u0144ska A, Kwiatkowska M, Chutora\u0144ski D, Wierzba-Bobrowicz T. Elevated serum and urine levels of progranulin (PGRN) as a predictor of microglia activation in the early phase of traumatic brain injury: a further link with the development of neurodegenerative diseases. Folia Neuropathol. 2021;59:81\u201390.","journal-title":"Folia Neuropathol"},{"key":"2684_CR36","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1038\/nature05017","volume":"442","author":"M Cruts","year":"2006","unstructured":"Cruts M, Gijselinck I, van der Zee J, Engelborghs S, Wils H, Pirici D, et al. Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature. 2006;442:920\u20134.","journal-title":"Nature"},{"key":"2684_CR37","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1038\/nature05016","volume":"442","author":"M Baker","year":"2006","unstructured":"Baker M, Mackenzie IR, Pickering-Brown SM, Gass J, Rademakers R, Lindholm C, et al. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature. 2006;442:916\u20139.","journal-title":"Nature"},{"key":"2684_CR38","first-page":"4639","volume":"24","author":"F Yin","year":"2010","unstructured":"Yin F, Dumont M, Banerjee R, Ma Y, Li H, Lin MT, et al. Behavioral deficits and progressive neuropathology in progranulin-deficient mice: a mouse model of frontotemporal dementia. FASEB J. 2010;24:4639\u201347.","journal-title":"FASEB J"},{"key":"2684_CR39","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2022.864391","volume":"13","author":"JM Poos","year":"2022","unstructured":"Poos JM, van den Berg E, Papma JM, van der Tholen FC, Seelaar H, Donker Kaat L, et al. Mindfulness-based stress reduction in pre-symptomatic genetic frontotemporal dementia: a pilot study. Front Psychiatry. 2022;13: 864391.","journal-title":"Front Psychiatry"},{"key":"2684_CR40","doi-asserted-by":"publisher","first-page":"43594","DOI":"10.1038\/srep43594","volume":"7","author":"K Zhang","year":"2017","unstructured":"Zhang K, Li YJ, Feng D, Zhang P, Wang YT, Li X, et al. Imbalance between TNF\u03b1 and progranulin contributes to memory impairment and anxiety in sleep-deprived mice. Sci Rep. 2017;7:43594.","journal-title":"Sci Rep"},{"key":"2684_CR41","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1002\/glia.23091","volume":"65","author":"L Menzel","year":"2017","unstructured":"Menzel L, Kleber L, Friedrich C, Hummel R, Dangel L, Winter J, et al. Progranulin protects against exaggerated axonal injury and astrogliosis following traumatic brain injury. Glia. 2017;65:278\u201392.","journal-title":"Glia"},{"key":"2684_CR42","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.intimp.2016.06.022","volume":"38","author":"X Xu","year":"2016","unstructured":"Xu X, Gou L, Zhou M, Yang F, Zhao Y, Feng T, et al. Progranulin protects against endotoxin-induced acute kidney injury by downregulating renal cell death and inflammatory responses in mice. Int Immunopharmacol. 2016;38:409\u201319.","journal-title":"Int Immunopharmacol"},{"key":"2684_CR43","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01662-z","author":"T Ni","year":"2022","unstructured":"Ni T, Zhu L, Wang S, Zhu W, Xue Y, Zhu Y, et al. Medial prefrontal cortex Notch1 signalling mediates methamphetamine-induced psychosis via Hes1-dependent suppression of GABA(B1) receptor expression. Mol Psychiatry. 2022. https:\/\/doi.org\/10.1038\/s41380-022-01662-z.","journal-title":"Mol Psychiatry"},{"key":"2684_CR44","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2022.892757","volume":"16","author":"M Liang","year":"2022","unstructured":"Liang M, Zhu L, Wang R, Su H, Ma D, Wang H, et al. Methamphetamine exposure in adolescent impairs memory of mice in adulthood accompanied by changes in neuroplasticity in the dorsal hippocampus. Front Cell Neurosci. 2022;16: 892757.","journal-title":"Front Cell Neurosci"},{"key":"2684_CR45","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402\u20138.","journal-title":"Methods"},{"key":"2684_CR46","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.bbi.2019.10.016","volume":"83","author":"J Wang","year":"2020","unstructured":"Wang J, Lai S, Li G, Zhou T, Wang B, Cao F, et al. Microglial activation contributes to depressive-like behavior in dopamine D3 receptor knockout mice. Brain Behav Immun. 2020;83:226\u201338.","journal-title":"Brain Behav Immun"},{"key":"2684_CR47","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/sj.npp.1301574","volume":"33","author":"C Pittenger","year":"2008","unstructured":"Pittenger C, Duman RS. Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology. 2008;33:88\u2013109.","journal-title":"Neuropsychopharmacology"},{"key":"2684_CR48","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.108694","volume":"108","author":"Y Su","year":"2022","unstructured":"Su Y, Liu Y, He D, Hu G, Wang H, Ye B, et al. Hordenine inhibits neuroinflammation and exerts neuroprotective effects via inhibiting NF-\u03baB and MAPK signaling pathways in vivo and in vitro. Int Immunopharmacol. 2022;108: 108694.","journal-title":"Int Immunopharmacol"},{"key":"2684_CR49","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2021109108","volume":"41","author":"A Reifschneider","year":"2022","unstructured":"Reifschneider A, Robinson S, van Lengerich B, Gn\u00f6rich J, Logan T, Heindl S, et al. Loss of TREM2 rescues hyperactivation of microglia, but not lysosomal deficits and neurotoxicity in models of progranulin deficiency. EMBO J. 2022;41: e109108.","journal-title":"EMBO J"},{"key":"2684_CR50","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.conb.2021.10.001","volume":"72","author":"S Amin","year":"2022","unstructured":"Amin S, Carling G, Gan L. New insights and therapeutic opportunities for progranulin-deficient frontotemporal dementia. Curr Opin Neurobiol. 2022;72:131\u20139.","journal-title":"Curr Opin Neurobiol"},{"key":"2684_CR51","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.30194","volume":"4","author":"A Benussi","year":"2021","unstructured":"Benussi A, Premi E, Gazzina S, Brattini C, Bonomi E, Alberici A, et al. Progression of behavioral disturbances and neuropsychiatric symptoms in patients with genetic frontotemporal dementia. JAMA Netw Open. 2021;4: e2030194.","journal-title":"JAMA Netw Open"},{"key":"2684_CR52","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1007\/s12035-012-8380-8","volume":"47","author":"G Kleinberger","year":"2013","unstructured":"Kleinberger G, Capell A, Haass C, Van Broeckhoven C. Mechanisms of granulin deficiency: lessons from cellular and animal models. Mol Neurobiol. 2013;47:337\u201360.","journal-title":"Mol Neurobiol"},{"key":"2684_CR53","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1177\/002215540004800713","volume":"48","author":"R Daniel","year":"2000","unstructured":"Daniel R, He Z, Carmichael KP, Halper J, Bateman A. Cellular localization of gene expression for progranulin. J Histochem Cytochem. 2000;48:999\u20131009.","journal-title":"J Histochem Cytochem"},{"key":"2684_CR54","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.neuroscience.2013.06.049","volume":"250","author":"Y Tanaka","year":"2013","unstructured":"Tanaka Y, Matsuwaki T, Yamanouchi K, Nishihara M. Increased lysosomal biogenesis in activated microglia and exacerbated neuronal damage after traumatic brain injury in progranulin-deficient mice. Neuroscience. 2013;250:8\u201319.","journal-title":"Neuroscience"},{"key":"2684_CR55","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/s00401-009-0616-y","volume":"119","author":"SB Naphade","year":"2010","unstructured":"Naphade SB, Kigerl KA, Jakeman LB, Kostyk SK, Popovich PG, Kuret J. Progranulin expression is upregulated after spinal contusion in mice. Acta Neuropathol. 2010;119:123\u201333.","journal-title":"Acta Neuropathol"},{"key":"2684_CR56","doi-asserted-by":"publisher","first-page":"3955","DOI":"10.1172\/JCI63113","volume":"122","author":"LH Martens","year":"2012","unstructured":"Martens LH, Zhang J, Barmada SJ, Zhou P, Kamiya S, Sun B, et al. Progranulin deficiency promotes neuroinflammation and neuron loss following toxin-induced injury. J Clin Invest. 2012;122:3955\u20139.","journal-title":"J Clin Invest"},{"key":"2684_CR57","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s13024-018-0288-y","volume":"13","author":"S Beel","year":"2018","unstructured":"Beel S, Herdewyn S, Fazal R, De Decker M, Moisse M, Robberecht W, et al. Progranulin reduces insoluble TDP-43 levels, slows down axonal degeneration and prolongs survival in mutant TDP-43 mice. Mol Neurodegener. 2018;13:55.","journal-title":"Mol Neurodegener"},{"key":"2684_CR58","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026454","volume":"6","author":"S Almeida","year":"2011","unstructured":"Almeida S, Zhou L, Gao FB. Progranulin, a glycoprotein deficient in frontotemporal dementia, is a novel substrate of several protein disulfide isomerase family proteins. PLoS ONE. 2011;6: e26454.","journal-title":"PLoS ONE"},{"key":"2684_CR59","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.neuroscience.2015.12.006","volume":"315","author":"TL Petkau","year":"2016","unstructured":"Petkau TL, Hill A, Leavitt BR. Core neuropathological abnormalities in progranulin-deficient mice are penetrant on multiple genetic backgrounds. Neuroscience. 2016;315:175\u201395.","journal-title":"Neuroscience"},{"key":"2684_CR60","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1136\/jnnp-2019-321954","volume":"91","author":"C Heller","year":"2020","unstructured":"Heller C, Foiani MS, Moore K, Convery R, Bocchetta M, Neason M, et al. Plasma glial fibrillary acidic protein is raised in progranulin-associated frontotemporal dementia. J Neurol Neurosurg Psychiatry. 2020;91:263\u201370.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2684_CR61","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1093\/hmg\/ddt534","volume":"23","author":"WC Lee","year":"2014","unstructured":"Lee WC, Almeida S, Prudencio M, Caulfield TR, Zhang YJ, Tay WM, et al. Targeted manipulation of the sortilin\u2013progranulin axis rescues progranulin haploinsufficiency. Hum Mol Genet. 2014;23:1467\u201378.","journal-title":"Hum Mol Genet"},{"key":"2684_CR62","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/1742-2094-8-65","volume":"8","author":"P Boss\u00f9","year":"2011","unstructured":"Boss\u00f9 P, Salani F, Alberici A, Archetti S, Bellelli G, Galimberti D, et al. Loss of function mutations in the progranulin gene are related to pro-inflammatory cytokine dysregulation in frontotemporal lobar degeneration patients. J Neuroinflammation. 2011;8:65.","journal-title":"J Neuroinflammation"},{"key":"2684_CR63","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1084\/jem.20091568","volume":"207","author":"F Yin","year":"2010","unstructured":"Yin F, Banerjee R, Thomas B, Zhou P, Qian L, Jia T, et al. Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice. J Exp Med. 2010;207:117\u201328.","journal-title":"J Exp Med"},{"key":"2684_CR64","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.stemcr.2014.12.001","volume":"4","author":"S Raitano","year":"2015","unstructured":"Raitano S, Ordov\u00e0s L, De Muynck L, Guo W, Espuny-Camacho I, Geraerts M, et al. Restoration of progranulin expression rescues cortical neuron generation in an induced pluripotent stem cell model of frontotemporal dementia. Stem Cell Rep. 2015;4:16\u201324.","journal-title":"Stem Cell Rep"},{"key":"2684_CR65","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1038\/nm.3672","volume":"20","author":"SS Minami","year":"2014","unstructured":"Minami SS, Min SW, Krabbe G, Wang C, Zhou Y, Asgarov R, et al. Progranulin protects against amyloid \u03b2 deposition and toxicity in Alzheimer\u2019s disease mouse models. Nat Med. 2014;20:1157\u201364.","journal-title":"Nat Med"},{"key":"2684_CR66","doi-asserted-by":"publisher","first-page":"5029","DOI":"10.1073\/pnas.1700477114","volume":"114","author":"G Krabbe","year":"2017","unstructured":"Krabbe G, Minami SS, Etchegaray JI, Taneja P, Djukic B, Davalos D, et al. Microglial NF\u03baB-TNF\u03b1 hyperactivation induces obsessive-compulsive behavior in mouse models of progranulin-deficient frontotemporal dementia. Proc Natl Acad Sci USA. 2017;114:5029\u201334.","journal-title":"Proc Natl Acad Sci USA"},{"key":"2684_CR67","doi-asserted-by":"publisher","DOI":"10.15252\/msb.202110473","volume":"18","author":"IL Ibarra","year":"2022","unstructured":"Ibarra IL, Ratnu VS, Gordillo L, Hwang IY, Mariani L, Weinand K, et al. Comparative chromatin accessibility upon BDNF stimulation delineates neuronal regulatory elements. Mol Syst Biol. 2022;18: e10473.","journal-title":"Mol Syst Biol"},{"key":"2684_CR68","doi-asserted-by":"publisher","first-page":"2320","DOI":"10.1038\/s41386-018-0115-8","volume":"43","author":"XB Wu","year":"2018","unstructured":"Wu XB, Jing PB, Zhang ZJ, Cao DL, Gao MH, Jiang BC, et al. Chemokine receptor CCR2 contributes to neuropathic pain and the associated depression via increasing NR2B-mediated currents in both D1 and D2 dopamine receptor-containing medium spiny neurons in the nucleus accumbens shell. Neuropsychopharmacology. 2018;43:2320\u201330.","journal-title":"Neuropsychopharmacology"},{"key":"2684_CR69","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1002\/glia.24175","volume":"70","author":"X Zheng","year":"2022","unstructured":"Zheng X, Mi T, Wang R, Zhang Z, Li W, Zhao J, et al. Progranulin deficiency promotes persistent neuroinflammation and causes regional pathology in the hippocampus following traumatic brain injury. Glia. 2022;70:1317\u201336.","journal-title":"Glia"},{"key":"2684_CR70","doi-asserted-by":"publisher","first-page":"3717","DOI":"10.1007\/s12035-016-9939-6","volume":"54","author":"Y Ma","year":"2017","unstructured":"Ma Y, Matsuwaki T, Yamanouchi K, Nishihara M. Progranulin protects hippocampal neurogenesis via suppression of neuroinflammatory responses under acute immune stress. Mol Neurobiol. 2017;54:3717\u201328.","journal-title":"Mol Neurobiol"},{"key":"2684_CR71","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/0306-4522(95)00259-L","volume":"69","author":"AM Magari\u00f1os","year":"1995","unstructured":"Magari\u00f1os AM, McEwen BS. Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: involvement of glucocorticoid secretion and excitatory amino acid receptors. Neuroscience. 1995;69:89\u201398.","journal-title":"Neuroscience"},{"key":"2684_CR72","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1002\/neu.1079","volume":"49","author":"CL Wellman","year":"2001","unstructured":"Wellman CL. Dendritic reorganization in pyramidal neurons in medial prefrontal cortex after chronic corticosterone administration. J Neurobiol. 2001;49:245\u201353.","journal-title":"J Neurobiol"},{"key":"2684_CR73","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/j.cell.2007.09.018","volume":"131","author":"V Krishnan","year":"2007","unstructured":"Krishnan V, Han MH, Graham DL, Berton O, Renthal W, Russo SJ, et al. Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell. 2007;131:391\u2013404.","journal-title":"Cell"},{"key":"2684_CR74","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1038\/nature07455","volume":"455","author":"V Krishnan","year":"2008","unstructured":"Krishnan V, Nestler EJ. The molecular neurobiology of depression. Nature. 2008;455:894\u2013902.","journal-title":"Nature"},{"key":"2684_CR75","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035115","volume":"7","author":"HS Suh","year":"2012","unstructured":"Suh HS, Choi N, Tarassishin L, Lee SC. Regulation of progranulin expression in human microglia and proteolysis of progranulin by matrix metalloproteinase-12 (MMP-12). PLoS ONE. 2012;7: e35115.","journal-title":"PLoS ONE"},{"key":"2684_CR76","doi-asserted-by":"publisher","first-page":"6543","DOI":"10.2147\/JIR.S339254","volume":"14","author":"YJ Lan","year":"2021","unstructured":"Lan YJ, Sam NB, Cheng MH, Pan HF, Gao J. Progranulin as a potential therapeutic target in immune-mediated diseases. J Inflamm Res. 2021;14:6543\u201356.","journal-title":"J Inflamm Res"},{"key":"2684_CR77","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s12974-020-01754-z","volume":"17","author":"L Wang","year":"2020","unstructured":"Wang L, Yin C, Liu T, Abdul M, Zhou Y, Cao JL, et al. Pellino1 regulates neuropathic pain as well as microglial activation through the regulation of MAPK\/NF-\u03baB signaling in the spinal cord. J Neuroinflammation. 2020;17:83.","journal-title":"J Neuroinflammation"},{"key":"2684_CR78","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s12865-020-00355-y","volume":"21","author":"L Liu","year":"2020","unstructured":"Liu L, Guo H, Song A, Huang J, Zhang Y, Jin S, et al. Progranulin inhibits LPS-induced macrophage M1 polarization via NF-\u043aB and MAPK pathways. BMC Immunol. 2020;21:32.","journal-title":"BMC Immunol"},{"key":"2684_CR79","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1111\/cns.13810","volume":"28","author":"S Sun","year":"2022","unstructured":"Sun S, Zhou J, Li Z, Wu Y, Wang H, Zheng Q, et al. Progranulin promotes hippocampal neurogenesis and alleviates anxiety-like behavior and cognitive impairment in adult mice subjected to cerebral ischemia. CNS Neurosci Ther. 2022;28:775\u201387.","journal-title":"CNS Neurosci Ther"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-022-02684-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12974-022-02684-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-022-02684-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T11:03:35Z","timestamp":1672571015000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-022-02684-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,29]]},"references-count":79,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["2684"],"URL":"https:\/\/doi.org\/10.1186\/s12974-022-02684-8","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-2060518\/v1","asserted-by":"object"}]},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,29]]},"assertion":[{"value":"13 September 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 December 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 December 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All the experiments were performed in accordance with legal and institutional guidelines and were carried out under ethics, consent and permissions of the Ethical Committee of Care and Use of Laboratory Animals at Xi\u2019an Jiaotong University and all efforts were made to minimize animal suffering.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing financial interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"318"}}