Caspase-12 is Expressed in Purkinje Neurons and Prevents Psychiatric-Like Behavior in Mice.

BDNF Caspase-12 Cerebellum Depression Purkinje neuron

Journal

Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963

Informations de publication

Date de publication:
18 Jul 2024
Historique:
received: 18 02 2024
accepted: 08 07 2024
medline: 18 7 2024
pubmed: 18 7 2024
entrez: 18 7 2024
Statut: aheadofprint

Résumé

Caspase-12 is a caspase family member for which functions in regulating cell death and inflammation have previously been suggested. In this study, we used caspase-12 lacZ reporter mice to elucidate the expression pattern of caspase-12 in order to obtain an idea about its possible in vivo function. Strikingly, these reporter mice showed that caspase-12 is expressed explicitly in Purkinje neurons of the cerebellum. As this observation suggested a function for caspase-12 in Purkinje neurons, we analyzed the brain and behavior of caspase-12 deficient mice in detail. Extensive histological analyses showed that caspase-12 was not crucial for establishing cerebellum structure or for maintaining Purkinje cell numbers. We then performed behavioral tests to investigate whether caspase-12 deficiency affects memory, motor, and psychiatric functions in mice. Interestingly, while the absence of caspase-12 did not affect memory and motor function, caspase-12 deficient mice showed depression and hyperactivity tendencies, together resembling manic behavior. Next, suggesting a possible molecular mechanistic explanation, we showed that caspase-12 deficient cerebella harbored diminished signaling through the brain-derived neurotrophic factor/tyrosine kinase receptor B/cyclic-AMP response binding protein axis, as well as strongly enhanced expression of the neuronal activity marker c-Fos. Thus, our study establishes caspase-12 expression in mouse Purkinje neurons and opens novel avenues of research to investigate the role of caspase-12 in regulating psychiatric behavior.

Identifiants

pubmed: 39023795
doi: 10.1007/s12035-024-04356-5
pii: 10.1007/s12035-024-04356-5
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : National Natural Science Foundation of China
ID : No.81802086
Organisme : National Natural Science Foundation of China
ID : No.81402918
Organisme : Natural Science Foundation of Jiangsu Province, China
ID : No.BK20211348
Organisme : Natural Science Foundation of Jiangsu Province, China
ID : No. BK20140228
Organisme : China Postdoctoral Science Foundation
ID : No.2016M591924

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Références

Van Opdenbosch N, Lamkanfi M (2019) Caspases in cell death, inflammation, and disease. Immunity 50(6):1352–1364. https://doi.org/10.1016/j.immuni.2019.05.020
doi: 10.1016/j.immuni.2019.05.020 pubmed: 31216460 pmcid: 6611727
Nakagawa T, Zhu H, Morishima N et al (2000) Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 403(6765):98–103. https://doi.org/10.1038/47513
doi: 10.1038/47513 pubmed: 10638761
Shiraishi H, Okamoto H, Yoshimura A, Yoshida H (2006) ER stress-induced apoptosis and caspase-12 activation occurs downstream of mitochondrial apoptosis involving Apaf-1. J Cell Sci 119(Pt 19):3958–3966. https://doi.org/10.1242/jcs.03160
doi: 10.1242/jcs.03160 pubmed: 16954146
Jimbo A, Fujita E, Kouroku Y et al (2003) ER stress induces caspase-8 activation, stimulating cytochrome c release and caspase-9 activation. Exp Cell Res 283(2):156–166. https://doi.org/10.1016/s0014-4827(02)00033-2
doi: 10.1016/s0014-4827(02)00033-2 pubmed: 12581736
Saleh M, Mathison JC, Wolinski MK et al (2006) Enhanced bacterial clearance and sepsis resistance in caspase-12-deficient mice. Nature 440(7087):1064–1068. https://doi.org/10.1038/nature04656
doi: 10.1038/nature04656 pubmed: 16625199
VandeWalle L, Jimenez Fernandez D, Demon D et al (2016) Does caspase-12 suppress inflammasome activation? Nature 534(7605):E1-4. https://doi.org/10.1038/nature17649
doi: 10.1038/nature17649
Salvamoser R, Brinkmann K, O’Reilly LA, Whitehead L, Strasser A, Herold MJ (2019) Characterisation of mice lacking the inflammatory caspases-1/11/12 reveals no contribution of caspase-12 to cell death and sepsis. Cell Death Differ 26(6):1124–1137. https://doi.org/10.1038/s41418-018-0188-2
doi: 10.1038/s41418-018-0188-2 pubmed: 30154447
Gierut JJ, Jacks TE, Haigis KM (2014) Whole-mount X-Gal staining of mouse tissues. Cold Spring Harb Protoc 2014(4):417–419. https://doi.org/10.1101/pdb.prot073452
doi: 10.1101/pdb.prot073452 pubmed: 24692489 pmcid: 4169236
Blanco MJ, Learte AIR, Marchena MA et al (2018) Tracing gene expression through detection of β-galactosidase activity in whole mouse embryos. J Vis Exp 136:e57785. https://doi.org/10.3791/57785
doi: 10.3791/57785
Furutama D, Morita N, Takano R et al (2010) Expression of the IP3R1 promoter-driven nls-lacZ transgene in Purkinje cell parasagittal arrays of developing mouse cerebellum. J Neurosci Res 88(13):2810–2825. https://doi.org/10.1002/jnr.22451
doi: 10.1002/jnr.22451 pubmed: 20632399
Furutama D, Shimoda K, Yoshikawa S, Miyawaki A, Furuichi T, Mikoshiba K (1996) Functional expression of the type 1 inositol 1,4,5-trisphosphate receptor promoter-lacZ fusion genes in transgenic mice. J Neurochem 66(5):1793–1801. https://doi.org/10.1046/j.1471-4159.1996.66051793.x
doi: 10.1046/j.1471-4159.1996.66051793.x pubmed: 8780003
Ohnishi M, Ochiai H, Matsuoka K et al (2017) Claudin domain containing 1 contributing to endothelial cell adhesion decreases in presence of cerebellar hemorrhage. J Neurosci Res 95(10):2051–2058. https://doi.org/10.1002/jnr.24040
doi: 10.1002/jnr.24040 pubmed: 28244141
Yang H, Huang LY, Zeng DY et al (2012) Decrease of intracellular chloride concentration promotes endothelial cell inflammation by activating nuclear factor-κB pathway. Hypertension 60(5):1287–1293. https://doi.org/10.1161/HYPERTENSIONAHA.112.198648
doi: 10.1161/HYPERTENSIONAHA.112.198648 pubmed: 23006728
Singh-Bains MK, Linke V, Austria MDR et al (2019) Altered microglia and neurovasculature in the Alzheimer’s disease cerebellum. Neurobiol Dis 132:104589. https://doi.org/10.1016/j.nbd.2019.104589
doi: 10.1016/j.nbd.2019.104589 pubmed: 31454549
Luck R, Karakatsani A, Shah B et al (2021) The angiopoietin-Tie2 pathway regulates Purkinje cell dendritic morphogenesis in a cell-autonomous manner. Cell Rep 36(7):109522. https://doi.org/10.1016/j.celrep.2021.109522
doi: 10.1016/j.celrep.2021.109522 pubmed: 34407407 pmcid: 9110807
Alvarez JC, Díaz C, Suárez C et al (1998) Neuronal loss in human medial vestibular nucleus. Anat Rec 251(4):431–438. https://doi.org/10.1002/(SICI)1097-0185(199808)251:4%3c431::AID-AR2%3e3.0.CO;2-V
doi: 10.1002/(SICI)1097-0185(199808)251:4<431::AID-AR2>3.0.CO;2-V pubmed: 9713981
Rogers DC, Fisher EM, Brown SD, Peters J, Hunter AJ, Martin JE (1997) Behavioral and functional analysis of mouse phenotype: SHIRPA, a proposed protocol for comprehensive phenotype assessment. Mamm Genome 8(10):711–713. https://doi.org/10.1007/s003359900551
doi: 10.1007/s003359900551 pubmed: 9321461
Lanznaster D, Mack JM, Coelho V et al (2017) Guanosine prevents anhedonic-like behavior and impairment in hippocampal glutamate transport following amyloid-β(1–40) administration in mice. Mol Neurobiol 54(7):5482–5496. https://doi.org/10.1007/s12035-016-0082-1
doi: 10.1007/s12035-016-0082-1 pubmed: 27599498
Antunes M, Biala G (2012) The novel object recognition memory: neurobiology, test procedure, and its modifications. Cogn Process 13(2):93–110. https://doi.org/10.1007/s10339-011-0430-z
doi: 10.1007/s10339-011-0430-z pubmed: 22160349
Yeshurun S, Rogers J, Short AK, Renoir T, Pang TY, Hannan AJ (2017) Elevated paternal glucocorticoid exposure modifies memory retention in female offspring. Psychoneuroendocrinol 83:9–18. https://doi.org/10.1016/j.psyneuen.2017.05.014
doi: 10.1016/j.psyneuen.2017.05.014
Deacon RMJ, Rawlins JNP (2006) T-maze alternation in the rodent. Nat Protoc 1(1):7–12. https://doi.org/10.1038/nprot.2006.2
doi: 10.1038/nprot.2006.2 pubmed: 17406205
Montag-Sallaz M, Montag D (2003) Severe cognitive and motor coordination deficits in tenascin-R-deficient mice. Genes Brain Behav 2(1):20–31. https://doi.org/10.1034/j.1601-183x.2003.00003.x
doi: 10.1034/j.1601-183x.2003.00003.x pubmed: 12882316
Bonetto A, Andersson DC, Waning DL (2015) Assessment of muscle mass and strength in mice. Bonekey Rep 4:732. https://doi.org/10.1038/bonekey.2015.101
doi: 10.1038/bonekey.2015.101 pubmed: 26331011 pmcid: 4549925
Carlson CG, Rutter J, Bledsoe C et al (2010) A simple protocol for assessing inter-trial and inter-examiner reliability for two noninvasive measures of limb muscle strength. J Neurosci Methods 186(2):226–230. https://doi.org/10.1016/j.jneumeth.2009.11.006
doi: 10.1016/j.jneumeth.2009.11.006 pubmed: 19917311
Can A, Dao DT, Arad M, Terrillion CE, Piantadosi SC, Gould TD (2012) The mouse forced swim test. J Vis Exp 59:e3638. https://doi.org/10.3791/3638
doi: 10.3791/3638
Yankelevitch-Yahav R, Franko M, Huly A, Doron R (2015) The forced swim test as a model of depressive-like behavior. J Vis Exp 97:e52587. https://doi.org/10.3791/52587
doi: 10.3791/52587
Yoshizaki K, Furuse T, Kimura R et al (2016) Paternal aging affects behavior in Pax6 mutant mice: a gene/environment interaction in understanding neurodevelopmental disorders. PLoS ONE 11(11):e0166665. https://doi.org/10.1371/journal.pone.0166665
doi: 10.1371/journal.pone.0166665 pubmed: 27855195 pmcid: 5113965
Hirano T (2018) Purkinje Neurons: development, morphology, and function. Cerebellum 17(6):699–700. https://doi.org/10.1007/s12311-018-0985-7
doi: 10.1007/s12311-018-0985-7 pubmed: 30284678
Lee JM, Kim TW, Park SS et al (2018) Treadmill exercise improves motor function by suppressing Purkinje cell loss in Parkinson disease rats. Int Neurourol J 22(Suppl 3):S147-155. https://doi.org/10.5213/inj.1836226.113
doi: 10.5213/inj.1836226.113 pubmed: 30396264 pmcid: 6234730
Apps R, Hawkes R (2009) Cerebellar cortical organization: a one-map hypothesis. Nat Rev Neurosci 10(9):670–681. https://doi.org/10.1038/nrn2698
doi: 10.1038/nrn2698 pubmed: 19693030
Karam SD, Burrows RC, Logan C, Koblar S, Pasquale EB, Bothwell M (2000) Eph receptors and ephrins in the developing chick cerebellum: relationship to sagittal patterning and granule cell migration. J Neurosci 20(17):6488–6500. https://doi.org/10.1523/JNEUROSCI.20-17-06488.2000
doi: 10.1523/JNEUROSCI.20-17-06488.2000 pubmed: 10964955 pmcid: 6772988
Larouche M, Beffert U, Herz J, Hawkes R (2008) The reelin receptors apoer2 and Vldlr coordinate the patterning of Purkinje cell topography in the developing mouse cerebellum. PLoS ONE 3(2):e1653. https://doi.org/10.1371/journal.pone.0001653
doi: 10.1371/journal.pone.0001653 pubmed: 18301736 pmcid: 2242849
Chung SH, Marzban H, Croci L, Consalez GG, Hawkes R (2008) Purkinje cell subtype specification in the cerebellar cortex: early B-cell factor 2 acts to repress the zebrin II-positive Purkinje cell phenotype. Neuroscience 153(3):721–732. https://doi.org/10.1016/j.neuroscience.2008.01.090
doi: 10.1016/j.neuroscience.2008.01.090 pubmed: 18403128
Sillitoe RV, Stephen D, Lao Z, Joyner AL (2008) Engrailed homeobox genes determine the organization of Purkinje cell sagittal stripe gene expression in the adult cerebellum. J Neurosci 28(47):12150–12162. https://doi.org/10.1523/JNEUROSCI.2059-08.2008
doi: 10.1523/JNEUROSCI.2059-08.2008 pubmed: 19020009 pmcid: 2864318
Corrales JD, Blaess S, Mahoney EM, Joyner AL (2006) The level of sonic hedgehog signaling regulates the complexity of cerebellar foliation. Development 133(9):1811–1821. https://doi.org/10.1242/dev.02351
doi: 10.1242/dev.02351 pubmed: 16571625
De Luca A, Cerrato V, Fucà E, Parmigiani E, Buffo A, Leto K (2016) Sonic hedgehog patterning during cerebellar development. Cell Mol Life Sci 73(2):291–303. https://doi.org/10.1007/s00018-015-2065-1
doi: 10.1007/s00018-015-2065-1 pubmed: 26499980
Pernice HF, Schieweck R, Jafari M et al (2020) Altered glutamate receptor ionotropic delta subunit 2 expression in Stau2-deficient cerebellar Purkinje cells in the adult brain. Int J Mol Sci 20(7):1797. https://doi.org/10.3390/ijms20071797
doi: 10.3390/ijms20071797
Switonski PM, Szlachcic WJ, Krzyzosiak WJ, Figiel M (2015) A new humanized ataxin-3 knock-in mouse model combines the genetic features, pathogenesis of neurons and glia and late disease onset of SCA3/MJD. Neurobiol Dis 73:174–188. https://doi.org/10.1016/j.nbd.2014.09.020
doi: 10.1016/j.nbd.2014.09.020 pubmed: 25301414
Wang L, Nomura M, Goto Y et al (2011) Smad2 protein disruption in the central nervous system leads to aberrant cerebellar development and early postnatal ataxia in mice. J Biol Chem 286(21):18766–18774. https://doi.org/10.1074/jbc.M111.223271
doi: 10.1074/jbc.M111.223271 pubmed: 21464123 pmcid: 3099693
Huang GJ, Edwards A, Tsai CY et al (2014) Ectopic cerebellar cell migration causes maldevelopment of Purkinje cells and abnormal motor behaviour in Cxcr4 null mice. PLoS ONE 9(2):e86471. https://doi.org/10.1371/journal.pone.0086471
doi: 10.1371/journal.pone.0086471 pubmed: 24516532 pmcid: 3917845
Wang JY, Yu IS, Huang CC et al (2015) Sun1 deficiency leads to cerebellar ataxia in mice. Dis Model Mech 8(8):957–967. https://doi.org/10.1242/dmm.019240
doi: 10.1242/dmm.019240 pubmed: 26035387 pmcid: 4527285
Florio M, Leto K, Muzio L et al (2012) Neurogenin 2 regulates progenitor cell-cycle progression and Purkinje cell dendritogenesis in cerebellar development. Development 139(13):2308–2320. https://doi.org/10.1242/dev.075861
doi: 10.1242/dev.075861 pubmed: 22669821 pmcid: 3367442
Lee M, Cho HS, Yoon KJ, Lee W, Moon HY (2020) Exercise-induced changes of gene expression in the cerebellum of aged mice. Biochem Biophys Res Commun 521(4):952–956. https://doi.org/10.1016/j.bbrc.2019.11.024
doi: 10.1016/j.bbrc.2019.11.024 pubmed: 31718796
Dutta S, Sengupta P (2016) Men and mice: relating their ages. Life Sci 152:244–248. https://doi.org/10.1016/j.lfs.2015.10.025
doi: 10.1016/j.lfs.2015.10.025 pubmed: 26596563
Galloway JN, Shaw C, Yu P et al (2014) CGG repeats in RNA modulate expression of TDP-43 in mouse and fly models of fragile X tremor ataxia syndrome. Hum Mol Genet 23(22):5906–5915. https://doi.org/10.1093/hmg/ddu314
doi: 10.1093/hmg/ddu314 pubmed: 24986919 pmcid: 4204772
Maloku E, Covelo IR, Hanbauer I et al (2010) Lower number of cerebellar Purkinje neurons in psychosis is associated with reduced reelin expression. Proc Natl Acad Sci U S A 107(9):4407–4411. https://doi.org/10.1073/pnas.0914483107
doi: 10.1073/pnas.0914483107 pubmed: 20150511 pmcid: 2840121
Donald S, Humby T, Fyfe I et al (2008) P-Rex2 regulates Purkinje cell dendrite morphology and motor coordination. Proc Natl Acad Sci U S A 105(11):4483–4488. https://doi.org/10.1073/pnas.0712324105
doi: 10.1073/pnas.0712324105 pubmed: 18334636 pmcid: 2393786
Zhang L, Chung SK, Chow BKC (2014) The knockout of secretin in cerebellar Purkinje cells impairs mouse motor coordination and motor learning. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol 39(6):1460–1468. https://doi.org/10.1038/npp.2013.344
doi: 10.1038/npp.2013.344
Tsumagari R, Kakizawa S, Kikunaga S, et al. (2020) DGKγ knock-out mice show impairments in cerebellar motor coordination, LTD, and the dendritic development of Purkinje cells through the activation of PKCγ. ENeuro. 7(2). https://doi.org/10.1523/ENEURO.0319-19.2020
Hoxha E, Tonini R, Montarolo F, Croci L, Consalez GG, Tempia F (2013) Motor dysfunction and cerebellar Purkinje cell firing impairment in Ebf2 null mice. Mol Cell Neurosci 52:51–61. https://doi.org/10.1016/j.mcn.2012.09.002
doi: 10.1016/j.mcn.2012.09.002 pubmed: 23000673
Trede K, Salvatore P, Baethge C, Gerhard A, Maggini C, Baldessarini RJ (2005) Manic-depressive illness: evolution in Kraepelin’s Textbook, 1883–1926. Harv Rev Psychiatry 13(3):155–178. https://doi.org/10.1080/10673220500174833
doi: 10.1080/10673220500174833 pubmed: 16020028
Lu B, Nagappan G, Lu Y (2014) BDNF and synaptic plasticity, cognitive function, and dysfunction. Handb Exp Pharmacol 220:223–250. https://doi.org/10.1007/978-3-642-45106-5_9
doi: 10.1007/978-3-642-45106-5_9 pubmed: 24668475
Martinowich K, Manji H, Lu B (2007) New insights into BDNF function in depression and anxiety. Nat Neurosci 10(9):1089–1093. https://doi.org/10.1038/nn1971
doi: 10.1038/nn1971 pubmed: 17726474
Duman RS, Voleti B (2012) Signaling pathways underlying the pathophysiology and treatment of depression: novel mechanisms for rapid-acting agents. Trends Neurosci 35(1):47–56. https://doi.org/10.1016/j.tins.2011.11.004
doi: 10.1016/j.tins.2011.11.004 pubmed: 22217452 pmcid: 3278537
Kung JC, Chen TC, Shyu BC, Hsiao S, Huang ACW (2010) Anxiety- and depressive-like responses and c-fos activity in preproenkephalin knockout mice: oversensitivity hypothesis of enkephalin deficit-induced posttraumatic stress disorder. J Biomed Sci 17(1):29. https://doi.org/10.1186/1423-0127-17-29
doi: 10.1186/1423-0127-17-29 pubmed: 20406487 pmcid: 2867948
de Medeiros MA, Carlos Reis L, Eugênio ML (2005) Stress-induced c-Fos expression is differentially modulated by dexamethasone, diazepam and imipramine. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol 30(7):1246–1256. https://doi.org/10.1038/sj.npp.1300694
doi: 10.1038/sj.npp.1300694
Calhoun CA, Lattouf C, Lewis V, Barrientos H, Donaldson ST (2023) Chronic mild stress induces differential depression-like symptoms and c-Fos and 5HT1A protein levels in high-anxiety female Long Evans rats. Behav Brain Res 438:114202. https://doi.org/10.1016/j.bbr.2022.114202
doi: 10.1016/j.bbr.2022.114202 pubmed: 36343695
Ionov ID, Pushinskaya II, Gorev NP, Frenkel DD (2019) Antidepressants upregulate c-Fos expression in the lateral entorhinal cortex and hippocampal dorsal subiculum: study in rats. Brain Res Bull 153:102–108. https://doi.org/10.1016/j.brainresbull.2019.08.015
doi: 10.1016/j.brainresbull.2019.08.015 pubmed: 31445055
Kim TK, Han PL (2016) Chronic stress and moderate physical exercise prompt widespread common activation and limited differential activation in specific brain regions. Neurochem Int 99:252–261. https://doi.org/10.1016/j.neuint.2016.08.007
doi: 10.1016/j.neuint.2016.08.007 pubmed: 27539656
Grinspun N, Fuentealba Y, Falcon R, Valdés JL (2019) c-Fos expression in the ascending arousal system induced by physical exercise in rats: implication for memory performance. Brain Res 1723:146376. https://doi.org/10.1016/j.brainres.2019.146376
doi: 10.1016/j.brainres.2019.146376 pubmed: 31408622
Wang T, Chen Y, Zou Y et al (2022) Locomotor hyperactivity in the early-stage Alzheimer’s disease-like pathology of APP/PS1 mice: associated with impaired polarization of astrocyte aquaporin 4. Aging Dis 13(5):1504–1522. https://doi.org/10.14336/AD.2022.0219
doi: 10.14336/AD.2022.0219 pubmed: 36186142 pmcid: 9466968

Auteurs

Lin-Yan Huang (LY)

School of Medical Technology, Xuzhou Key Laboratory of Laboratory Diagnostics, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, People's Republic of China.
VIB Center for Inflammation Research, Zwijnaarde, Belgium.
Department of Internal Medicine and Paediatrics, Ghent University, Ghent, Belgium.

Yi-Ning Liu (YN)

School of Medical Technology, Xuzhou Key Laboratory of Laboratory Diagnostics, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, People's Republic of China.

Jie Chen (J)

School of Medical Technology, Xuzhou Key Laboratory of Laboratory Diagnostics, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, People's Republic of China.
Department of Laboratory Medicine, The Affiliated Hospital of Xuzhou Medical University, Huaihai West Road 99, Xuzhou, 221002, China.

Hai-Xue Zhu (HX)

Department of Ophthalmology, The Affiliated Huai'an Hospital of Xuzhou Medical University, No.62 Huaihai South Road, Huai'an, 223001, Jiangsu, People's Republic of China.

Li-Li Li (LL)

School of Medical Technology, Xuzhou Key Laboratory of Laboratory Diagnostics, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, People's Republic of China.

Zhi-Yan Liang (ZY)

School of Medical Technology, Xuzhou Key Laboratory of Laboratory Diagnostics, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, People's Republic of China.

Jin-Xiu Song (JX)

Department of Pharmacology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, People's Republic of China.

Yu-Jie Li (YJ)

Department of Clinical Laboratory, Kunshan First People's Hospital, Kunshan, Jiangsu, 215300, People's Republic of China.

Zhao-Li Hu (ZL)

Research Center for Biochemistry and Molecular Biology and Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical University, Xuzhou, People's Republic of China.

Dieter Demon (D)

VIB Center for Inflammation Research, Zwijnaarde, Belgium.
Department of Internal Medicine and Paediatrics, Ghent University, Ghent, Belgium.

Andy Wullaert (A)

VIB Center for Inflammation Research, Zwijnaarde, Belgium.
Department of Internal Medicine and Paediatrics, Ghent University, Ghent, Belgium.
Cell Death Signaling Lab, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.

Wan Wang (W)

School of Medical Technology, Xuzhou Key Laboratory of Laboratory Diagnostics, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, People's Republic of China.

Su-Hua Qi (SH)

School of Medical Technology, Xuzhou Key Laboratory of Laboratory Diagnostics, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, People's Republic of China. suhuaqi@xzhmu.edu.cn.

Classifications MeSH