Astrocyte-derived apolipoprotein D is required for neuronal survival in Parkinson's disease.


Journal

NPJ Parkinson's disease
ISSN: 2373-8057
Titre abrégé: NPJ Parkinsons Dis
Pays: United States
ID NLM: 101675390

Informations de publication

Date de publication:
02 Aug 2024
Historique:
received: 05 02 2024
accepted: 12 07 2024
medline: 3 8 2024
pubmed: 3 8 2024
entrez: 2 8 2024
Statut: epublish

Résumé

Apolipoprotein D (ApoD), a lipocalin transporter of small hydrophobic molecules, plays an essential role in several neurodegenerative diseases. It was reported that increased immunostaining for ApoD of glial cells surrounding dopaminergic (DAergic) neurons was observed in the brains of Parkinson's disease (PD) patients. Although preliminary findings supported the role of ApoD in neuroprotection, its derivation and effects on the degeneration of nigral DAergic neurons are largely unknown. In the present study, we observed that ApoD levels released from astrocytes were increased in PD models both in vivo and in vitro. When co-cultured with astrocytes, due to the increased release of astrocytic ApoD, the survival rate of primary cultured ventral midbrain (VM) neurons was significantly increased with 1-methyl-4-phenylpyridillium ion (MPP

Identifiants

pubmed: 39095480
doi: 10.1038/s41531-024-00753-8
pii: 10.1038/s41531-024-00753-8
doi:

Types de publication

Journal Article

Langues

eng

Pagination

143

Subventions

Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 32171131
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 32371013
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82071429
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 32371181
Organisme : Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation)
ID : 2021ZDSYS11
Organisme : Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation)
ID : ZR2019ZD31
Organisme : Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation)
ID : ZR2020QH125
Organisme : Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation)
ID : ZR2022MC098

Informations de copyright

© 2024. The Author(s).

Références

Chen, B. et al. Interactions between iron and alpha-synuclein pathology in Parkinson’s disease. Free Radic. Biol. Med. 141, 253–260 (2019).
pubmed: 31233777 doi: 10.1016/j.freeradbiomed.2019.06.024
De Virgilio, A. et al. Parkinson’s disease: autoimmunity and neuroinflammation. Autoimmun. Rev. 15, 1005–1011 (2016).
pubmed: 27497913 doi: 10.1016/j.autrev.2016.07.022
Jiang, H. et al. Brain iron metabolism dysfunction in Parkinson’s disease. Mol. Neurobiol. 54, 3078–3101 (2017).
pubmed: 27039308 doi: 10.1007/s12035-016-9879-1
Bi, M. et al. Deficient immunoproteasome assembly drives gain of α-synuclein pathology in Parkinson’s disease. Redox Biol. 47, 102167 (2021).
pubmed: 34662812 pmcid: 8577461 doi: 10.1016/j.redox.2021.102167
Jiao, L. et al. Early low-dose ghrelin intervention via miniosmotic pumps could protect against the progressive dopaminergic neuron loss in Parkinson’s disease mice. Neurobiol. Aging 101, 70–78 (2021).
pubmed: 33582568 doi: 10.1016/j.neurobiolaging.2021.01.011
Jia, F. et al. High dietary iron supplement induces the nigrostriatal dopaminergic neurons lesion in transgenic mice expressing mutant A53T human alpha-synuclein. Front Aging Neurosci. 10, 97 (2018).
pubmed: 29681846 pmcid: 5897504 doi: 10.3389/fnagi.2018.00097
Booth, H. D. E., Hirst, W. D. & Wade-Martins, R. The role of astrocyte dysfunction in Parkinson’s disease pathogenesis. Trends Neurosci. 40, 358–370 (2017).
pubmed: 28527591 pmcid: 5462417 doi: 10.1016/j.tins.2017.04.001
Sorrentino, Z. A., Giasson, B. I. & Chakrabarty, P. α-Synuclein and astrocytes: tracing the pathways from homeostasis to neurodegeneration in Lewy body disease. Acta Neuropathol. 138, 1–21 (2019).
pubmed: 30798354 pmcid: 6571045 doi: 10.1007/s00401-019-01977-2
Belanger, M., Allaman, I. & Magistretti, P. J. Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab. 14, 724–738 (2011).
pubmed: 22152301 doi: 10.1016/j.cmet.2011.08.016
Kuter, K. et al. Astrocyte support is important for the compensatory potential of the nigrostriatal system neurons during early neurodegeneration. J. Neurochem. 148, 63–79 (2019).
pubmed: 30295916 doi: 10.1111/jnc.14605
Wei, Y. et al. Pyridoxine induces glutathione synthesis via PKM2-mediated Nrf2 transactivation and confers neuroprotection. Nat. Commun. 11, 941 (2020).
pubmed: 32071304 pmcid: 7029000 doi: 10.1038/s41467-020-14788-x
Sofroniew, M. V. & Vinters, H. V. Astrocytes: biology and pathology. Acta Neuropathol. 119, 7–35 (2010).
pubmed: 20012068 doi: 10.1007/s00401-009-0619-8
Lin, L. F. et al. GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 260, 1130–1132 (1993).
pubmed: 8493557 doi: 10.1126/science.8493557
Schaar, D. G. et al. Regional and cell-specific expression of GDNF in rat brain. Exp. Neurol. 124, 368–371 (1993).
pubmed: 8287932 doi: 10.1006/exnr.1993.1207
Terrisse, L. et al. Increased levels of apolipoprotein D in cerebrospinal fluid and hippocampus of Alzheimer’s patients. J. Neurochem. 71, 1643–1650 (1998).
pubmed: 9751198 doi: 10.1046/j.1471-4159.1998.71041643.x
Kalman, J. et al. Apolipoprotein D in the aging brain and in Alzheimer’s dementia. Neurol. Res. 22, 330–336 (2000).
pubmed: 10874678 doi: 10.1080/01616412.2000.11740678
Desai, P. P. et al. Apolipoprotein D is a component of compact but not diffuse amyloid-beta plaques in Alzheimer’s disease temporal cortex. Neurobiol. Dis. 20, 574–582 (2005).
pubmed: 15916898 doi: 10.1016/j.nbd.2005.04.012
Rickhag, M. et al. Comprehensive regional and temporal gene expression profiling of the rat brain during the first 24 h after experimental stroke identifies dynamic ischemia-induced gene expression patterns, and reveals a biphasic activation of genes in surviving tissue. J. Neurochem. 96, 14–29 (2006).
pubmed: 16300643 doi: 10.1111/j.1471-4159.2005.03508.x
Rickhag, M. et al. Apolipoprotein D is elevated in oligodendrocytes in the peri-infarct region after experimental stroke: influence of enriched environment. J. Cereb. Blood Flow. Metab. 28, 551–562 (2008).
pubmed: 17851453 doi: 10.1038/sj.jcbfm.9600552
Thomas, E. A. et al. Increased CNS levels of apolipoprotein D in schizophrenic and bipolar subjects: implications for the pathophysiology of psychiatric disorders. Proc. Natl Acad. Sci. USA 98, 4066–4071 (2001).
pubmed: 11274430 pmcid: 31180 doi: 10.1073/pnas.071056198
Mahadik, S. P. et al. Elevated plasma level of apolipoprotein D in schizophrenia and its treatment and outcome. Schizophr. Res. 58, 55–62 (2002).
pubmed: 12363390 doi: 10.1016/S0920-9964(01)00378-4
Thomas, E. A., George, R. C. & Sutcliffe, J. G. Apolipoprotein D modulates arachidonic acid signaling in cultured cells: implications for psychiatric disorders. Prostaglandins Leukot. Ess. Fat. Acids 69, 421–427 (2003).
doi: 10.1016/j.plefa.2003.08.014
Waldner, A. et al. Apolipoprotein D Concentration in Human Plasma during Aging and in Parkinson’s Disease: A Cross-Sectional Study. Parkinsons Dis. 3751516 (2018).
Ordonez, C. et al. Apolipoprotein D expression in substantia nigra of Parkinson disease. Histol. Histopathol. 21, 361–366 (2006).
pubmed: 16437381
Rassart, E. et al. Apolipoprotein D. Gene 756, 144874 (2020).
pubmed: 32554047 pmcid: 8011330 doi: 10.1016/j.gene.2020.144874
Bhatia, S. et al. Increased apolipoprotein D dimer formation in Alzheimer’s disease hippocampus is associated with lipid conjugated diene levels. J. Alzheimers Dis. 35, 475–486 (2013).
pubmed: 23455990 doi: 10.3233/JAD-122278
Rassart, E. et al. Apolipoprotein D. Biochim. Biophys. Acta 1482, 185–198 (2000).
pubmed: 11058760 doi: 10.1016/S0167-4838(00)00162-X
Boyles, J. K. et al. A role for apolipoprotein E, apolipoprotein A-I, and low density lipoprotein receptors in cholesterol transport during regeneration and remyelination of the rat sciatic nerve. J. Clin. Invest 83, 1015–1031 (1989).
pubmed: 2493483 pmcid: 303779 doi: 10.1172/JCI113943
Boyles, J. K. et al. Identification, characterization, and tissue distribution of apolipoprotein D in the rat. J. Lipid Res 31, 2243–2256 (1990).
pubmed: 2090718 doi: 10.1016/S0022-2275(20)42112-1
Pascua-Maestro, R. et al. Extracellular vesicles secreted by astroglial cells transport apolipoprotein D to neurons and mediate neuronal survival upon oxidative stress. Front Cell Neurosci. 12, 526 (2018).
pubmed: 30687015 doi: 10.3389/fncel.2018.00526
García-Mateo, N. et al. Schwann cell-derived Apolipoprotein D controls the dynamics of post-injury myelin recognition and degradation. Front Cell Neurosci. 8, 374 (2014).
pubmed: 25426024 pmcid: 4227524
Ganfornina, M. D. et al. Apolipoprotein D is involved in the mechanisms regulating protection from oxidative stress. Aging Cell 7, 506–515 (2008).
pubmed: 18419796 doi: 10.1111/j.1474-9726.2008.00395.x
Navarro, J. A. et al. Altered lipid metabolism in a Drosophila model of Friedreich’s ataxia. Hum. Mol. Genet. 19, 2828–2840 (2010).
pubmed: 20460268 doi: 10.1093/hmg/ddq183
Bajo-Graneras, R. et al. Apolipoprotein D mediates autocrine protection of astrocytes and controls their reactivity level, contributing to the functional maintenance of paraquat-challenged dopaminergic systems. Glia 59, 1551–1566 (2011).
pubmed: 21688324 doi: 10.1002/glia.21200
Belyi, V. A. et al. The origins and evolution of the p53 family of genes. Cold Spring Harb. Perspect. Biol. 2, a001198 (2010).
pubmed: 20516129 pmcid: 2869528 doi: 10.1101/cshperspect.a001198
Yuan, Z. M. et al. p73 is regulated by tyrosine kinase c-Abl in the apoptotic response to DNA damage. Nature 399, 814–817 (1999).
pubmed: 10391251 doi: 10.1038/21704
Agami, R. et al. Interaction of c-Abl and p73alpha and their collaboration to induce apoptosis. Nature 399, 809–813 (1999).
pubmed: 10391250 doi: 10.1038/21697
Satija, Y. K. & Das, S. Tyr99 phosphorylation determines the regulatory milieu of tumor suppressor p73. Oncogene 35, 513–527 (2016).
pubmed: 25893286 doi: 10.1038/onc.2015.111
Drayna, D. et al. Cloning and expression of human apolipoprotein D cDNA. J. Biol. Chem. 261, 16535–16539 (1986).
pubmed: 3453108 doi: 10.1016/S0021-9258(18)66599-8
Li, H. et al. Cerebral apolipoprotein-D is hypoglycosylated compared to peripheral tissues and is variably expressed in mouse and human brain regions. PLoS ONE 11, e0148238 (2016).
pubmed: 26829325 pmcid: 4734669 doi: 10.1371/journal.pone.0148238
Séguin, D., Desforges, M. & Rassart, E. Molecular characterization and differential mRNA tissue distribution of mouse apolipoprotein D. Brain Res Mol. Brain Res. 30, 242–250 (1995).
pubmed: 7637575 doi: 10.1016/0169-328X(95)00008-G
Do Carmo, S. et al. Human apolipoprotein D overexpression in transgenic mice induces insulin resistance and alters lipid metabolism. Am. J. Physiol. Endocrinol. Metab. 296, E802–E811 (2009).
pubmed: 19176353 doi: 10.1152/ajpendo.90725.2008
Cofer, S. & Ross, S. R. The murine gene encoding apolipoprotein D exhibits a unique expression pattern as compared to other species. Gene 171, 261–263 (1996).
pubmed: 8666283 doi: 10.1016/0378-1119(96)00099-6
Dassati, S., Waldner, A. & Schweigreiter, R. Apolipoprotein D takes center stage in the stress response of the aging and degenerative brain. Neurobiol. Aging 35, 1632–1642 (2014).
pubmed: 24612673 pmcid: 3988949 doi: 10.1016/j.neurobiolaging.2014.01.148
Smith, K. M., Lawn, R. M. & Wilcox, J. N. Cellular localization of apolipoprotein D and lecithin: cholesterol acyltransferase mRNA in rhesus monkey tissues by in situ hybridization. J. Lipid Res. 31, 995–1004 (1990).
pubmed: 2373967 doi: 10.1016/S0022-2275(20)42739-7
Flower, D. R. The lipocalin protein family: structure and function. Biochem. J. 318, 1–14 (1996).
pubmed: 8761444 pmcid: 1217580 doi: 10.1042/bj3180001
Eichinger, A. et al. Structural insight into the dual ligand specificity and mode of high density lipoprotein association of apolipoprotein D. J. Biol. Chem. 282, 31068–31075 (2007).
pubmed: 17699160 doi: 10.1074/jbc.M703552200
Morais Cabral, J. H. et al. Arachidonic acid binds to apolipoprotein D: implications for the protein’s function. FEBS Lett. 366, 53–56 (1995).
pubmed: 7789516 doi: 10.1016/0014-5793(95)00484-Q
Ruiz, M. et al. Lipid-binding properties of human ApoD and Lazarillo-related lipocalins: functional implications for cell differentiation. Febs j. 280, 3928–3943 (2013).
pubmed: 23777559 doi: 10.1111/febs.12394
Vogt, M. & Skerra, A. Bacterially produced apolipoprotein D binds progesterone and arachidonic acid, but not bilirubin or E-3M2H. J. Mol. Recognit. 14, 79–86 (2001).
pubmed: 11180564 doi: 10.1002/1099-1352(200101/02)14:1<79::AID-JMR521>3.0.CO;2-4
Heikkila, R. E., Hess, A. & Duvoisin, R. C. Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine in mice. Science 224, 1451–1453 (1984).
pubmed: 6610213 doi: 10.1126/science.6610213
Langston, J. W. & Ballard, P. Parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): implications for treatment and the pathogenesis of Parkinson’s disease. Can. J. Neurol. Sci. 11, 160–165 (1984).
pubmed: 6608979 doi: 10.1017/S0317167100046333
Pickrell, A. M. & Youle, R. J. The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease. Neuron 85, 257–273 (2015).
pubmed: 25611507 pmcid: 4764997 doi: 10.1016/j.neuron.2014.12.007
Mani, S. & Sevanan, M. A systematic review of molecular approaches that link mitochondrial dysfunction and neuroinflammation in Parkinson’s disease. Neurol. Sci. 42, 4459–4469 (2021).
pubmed: 34480241 doi: 10.1007/s10072-021-05551-1
Jovanovic-Tucovic, M. et al. AMP-activated protein kinase inhibits MPP+-induced oxidative stress and apoptotic death of SH-SY5Y cells through sequential stimulation of Akt and autophagy. Eur. J. Pharm. 863, 172677 (2019).
doi: 10.1016/j.ejphar.2019.172677
Kerr, J. F., Wyllie, A. H. & Currie, A. R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 26, 239–257 (1972).
pubmed: 4561027 pmcid: 2008650 doi: 10.1038/bjc.1972.33
Reed, J. C. Bcl-2 and the regulation of programmed cell death. J. Cell Biol. 124, 1–6 (1994).
pubmed: 8294493 doi: 10.1083/jcb.124.1.1
Zhang, Y. et al. Antioxidant activities of recombinant amphioxus (Branchiostoma belcheri) apolipoprotein D. Mol. Biol. Rep. 38, 1847–1851 (2011).
pubmed: 20848217 doi: 10.1007/s11033-010-0301-1
Sacks, D. et al. Multisociety consensus quality improvement revised consensus statement for endovascular therapy of acute ischemic stroke. Int J. Stroke 13, 612–632 (2018).
pubmed: 29786478
Yoshikawa, A. et al. Deletion of Atf6α impairs astroglial activation and enhances neuronal death following brain ischemia in mice. J. Neurochem. 132, 342–353 (2015).
pubmed: 25351847 doi: 10.1111/jnc.12981
Morale, M. C. et al. Estrogen, neuroinflammation and neuroprotection in Parkinson’s disease: glia dictates resistance versus vulnerability to neurodegeneration. Neuroscience 138, 869–878 (2006).
pubmed: 16337092 doi: 10.1016/j.neuroscience.2005.07.060
Song, Y. J. et al. Degeneration in different parkinsonian syndromes relates to astrocyte type and astrocyte protein expression. J. Neuropathol. Exp. Neurol. 68, 1073–1083 (2009).
pubmed: 19918119 doi: 10.1097/NEN.0b013e3181b66f1b
Zigmond, M. J. et al. Neurorestoration by physical exercise: moving forward. Parkinsonism Relat. Disord. 18(Suppl 1), S147–S150 (2012).
pubmed: 22166417 doi: 10.1016/S1353-8020(11)70046-3
Zigmond, M. J. et al. Triggering endogenous neuroprotective processes through exercise in models of dopamine deficiency. Parkinsonism Relat. Disord. 15(Suppl 3), S42–S45 (2009).
pubmed: 20083005 doi: 10.1016/S1353-8020(09)70778-3
Cahoy, J. D. et al. A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J. Neurosci. 28, 264–278 (2008).
pubmed: 18171944 pmcid: 6671143 doi: 10.1523/JNEUROSCI.4178-07.2008
Zeisel, A. et al. Molecular architecture of the mouse nervous system. Cell 174, 999–1014.e1022 (2018).
pubmed: 30096314 pmcid: 6086934 doi: 10.1016/j.cell.2018.06.021
Pascua-Maestro, R. & Diez-Hermano, S. Protecting cells by protecting their vulnerable lysosomes: identification of a new mechanism for preserving lysosomal functional integrity upon oxidative stress. PLoS Genet. 13, e1006603 (2017).
pubmed: 28182653 pmcid: 5325589 doi: 10.1371/journal.pgen.1006603
Sahin, E. et al. Telomere dysfunction induces metabolic and mitochondrial compromise. Nature 470, 359–365 (2011).
pubmed: 21307849 pmcid: 3741661 doi: 10.1038/nature09787
Omran, Z. et al. Targeting post-translational modifications of the p73 protein: a promising therapeutic strategy for tumors. Cancers (Basel). 13, 1916 (2021).
pubmed: 33921128 pmcid: 8071514 doi: 10.3390/cancers13081916
Gong, J. G. et al. The tyrosine kinase c-Abl regulates p73 in apoptotic response to cisplatin-induced DNA damage. Nature 399, 806–809 (1999).
pubmed: 10391249 doi: 10.1038/21690
Boyles, J. K., Notterpek, L. M. & Anderson, L. J. Accumulation of apolipoproteins in the regenerating and remyelinating mammalian peripheral nerve. Identification of apolipoprotein D, apolipoprotein A-IV, apolipoprotein E, and apolipoprotein A-I. J. Biol. Chem. 265, 17805–17815 (1990).
pubmed: 2120218 doi: 10.1016/S0021-9258(18)38235-8
Jiménez-Palomares, M. et al. Genetic deficiency of apolipoprotein D in the mouse is associated with nonfasting hypertriglyceridemia and hyperinsulinemia. Metabolism 60, 1767–1774 (2011).
pubmed: 21632073 doi: 10.1016/j.metabol.2011.04.013
Desmarais, F. et al. Apolipoprotein D overexpression alters hepatic prostaglandin and omega fatty acid metabolism during the development of a non-inflammatory hepatic steatosis. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1864, 522–531 (2019).
pubmed: 30630053 doi: 10.1016/j.bbalip.2019.01.001
Liu, Z., Chang, G. Q. & Leibowitz, S. F. Apolipoprotein D interacts with the long-form leptin receptor: a hypothalamic function in the control of energy homeostasis. FASEB J. 15, 1329–1331 (2001).
pubmed: 11344130 doi: 10.1096/fj.00-0530fje
Perdomo, G. et al. A role of apolipoprotein D in triglyceride metabolism. J. Lipid Res. 51, 1298–1311 (2010).
pubmed: 20124557 pmcid: 3035493 doi: 10.1194/jlr.M001206
El-Darzi, N. & Mast, N. Studies of ApoD (-/-) and ApoD (-/-) ApoE (-/-) mice uncover the APOD significance for retinal metabolism, function, and status of chorioretinal blood vessels. Cell Mol. Life Sci. 78, 963–983 (2021).
pubmed: 32440710 doi: 10.1007/s00018-020-03546-3
Upadhya, R. et al. Astrocyte-derived extracellular vesicles: Neuroreparative properties and role in the pathogenesis of neurodegenerative disorders. J. Control Release 323, 225–239 (2020).
pubmed: 32289328 pmcid: 7299747 doi: 10.1016/j.jconrel.2020.04.017
Gaven, F., Marin, P. & Claeysen, S. Primary culture of mouse dopaminergic neurons. J. Vis. Exp. 8, e51751 (2014).
Gottschling, C. et al. The Indirect Neuron-astrocyte Coculture Assay: An In Vitro Set-up for the Detailed Investigation of Neuron-glia Interactions. J. Vis. Exp. 14, 54757 (2016).
Pioli, E. Y. et al. Differential behavioral effects of partial bilateral lesions of ventral tegmental area or substantia nigra pars compacta in rats. Neuroscience 153, 1213–1224 (2008).
pubmed: 18455318 doi: 10.1016/j.neuroscience.2008.01.084
Engeln, M. et al. Reinforcing properties of Pramipexole in normal and parkinsonian rats. Neurobiol. Dis. 49, 79–86 (2013).
pubmed: 22940424 doi: 10.1016/j.nbd.2012.08.005
Zhang, Z. et al. Lesion of medullary catecholaminergic neurons is associated with cardiovascular dysfunction in rotenone-induced Parkinson’s disease rats. Eur. J. Neurosci. 42, 2346–2355 (2015).
pubmed: 26153521 doi: 10.1111/ejn.13012
Bastide, M. F. et al. Immediate-early gene expression in structures outside the basal ganglia is associated to l-DOPA-induced dyskinesia. Neurobiol. Dis. 62, 179–192 (2014).
pubmed: 24103779 doi: 10.1016/j.nbd.2013.09.020
Jiang, H. et al. Neuroprotective effects of iron chelator Desferal on dopaminergic neurons in the substantia nigra of rats with iron-overload. Neurochem. Int. 49, 605–609 (2006).
pubmed: 16806586 doi: 10.1016/j.neuint.2006.04.015

Auteurs

Yingying Dai (Y)

Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, School of Basic Medicine, Qingdao University, Qingdao, China.

Mingxia Bi (M)

Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, School of Basic Medicine, Qingdao University, Qingdao, China.

Qian Jiao (Q)

Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, School of Basic Medicine, Qingdao University, Qingdao, China.

Xixun Du (X)

Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, School of Basic Medicine, Qingdao University, Qingdao, China.

Chunling Yan (C)

Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, School of Basic Medicine, Qingdao University, Qingdao, China. chunlingyan@qdu.edu.cn.

Hong Jiang (H)

Qingdao Hospital (Qingdao Municipal Hospital), University of Health and Rehabilitation Sciences, Qingdao, China. jianghong@uor.edu.cn.

Classifications MeSH