Advanced Search

Journal of Traditional Chinese Medicine >

2025 , Vol. 45 >Issue 3: 571 - 585

DOI: https://doi.org/10.19852/j.cnki.jtcm.2025.03.012

Identifying potential biomarkers in the hippocampus of chronic fatigue syndrome rats treated with moxibustion at Zusanli (ST36): a proteomics study

  • Chuwen FENG ,
  • Chaoran LI ,
  • Yan Yang ,
  • Yuanyuan QU ,
  • Zhongren SUN ,
  • Weibo SUN ,
  • Tingting LIU ,
  • Shulin LI ,
  • Tiansong Yang
Expand
  • 1 Rehabilitation Department Ⅱ, the First Affiliated Hospital of Heilongjiang University of Chinese Medicine; Harbin 150040, China
    2 Heilongjiang Province Key Laboratory of Traditional Chinese Medicine Information, Harbin 150040, China
    3 Department of Acupuncture, Zhejiang Chinese Medical University, Hangzhou 310000, China
    4 College of Basic Medicine of Heilongjiang University of Chinese Medicine, Harbin 150040, China
    5 Graduate School of Heilongjiang University of Chinese Medicine, Harbin 150040, China
    6 Graduate School of Harbin Medical University, Harbin 150040, China

Received date: 2024-11-22

  Accepted date: 2025-02-25

  Online published: 2025-05-21

Supported by

National Natural Science Foundation of China projects: Research on the Mechanism of Moxibustion Activating Calcium/ Calmodulin-dependent Protein Kinase ⅡPhosphorylation Mediating Long-term Potentiation to Regulate Synaptic Plasticity in the Treatment of Chronic Fatigue Syndrome Cognitive Impairment(82305394);Research on the Mechanism of Electroacupuncture Regulating Murine Double Minute 2 Ubiquitination Postsynaptic Density Protein 95 Levels to Reshape the Synaptic Structure of Hippocampal Neurons and Improve Chronic Fatigue Syndrome Cognitive Impairment(82074539);Outstanding Youth Project of Heilongjiang Provincial Natural Science Foundation: the Mechanism of Moxibustion in Improving Chronic Fatigue Syndrome Cognitive Impairment by Regulating Calcium/Calmodulin-dependent Protein Kinase II-mediated Long-Term Potentiation(YQ2023H019);Youth Talent Support Project of the Chinese Association of Traditional Chinese Medicine: Research on the Molecular Pathways of Moxibustion at the Zusanli (ST36) Point in Regulating Synaptic Plasticity to Improve Chronic Fatigue Syndrome Cognitive Impairment(2023-QNRC2-A04);China Postdoctoral Science Foundation: Research on the Mechanism of Moxibustion in Regulating Mitochondrial Autophagy Mediating Microglial Polarization to Promote Synaptic Remodeling in Chronic Fatigue Syndrome Cognitive Impairment(2024MD763980);Post-doctoral Program of Heilongjiang Province: based on the Calcium/Calmodulin-dependent Protein Kinase II/Parkin/NLR Family Pyrin Domain Containing 3 Signaling Axis to Explore the Mechanism of Moxibustion in Mitochondrial Autophagy Mediating Microglial Polarization to Promote Synaptic Remodeling in Chronic Fatigue Syndrome Cognitive Impairment(LBH-TZ2420);Study on the Mechanism of Moxibustion at the Zusanli (ST36) Regulating Long-Term Potentiation to Promote Synaptic Remodeling and Improve Cognitive Impairment in Chronic Fatigue Syndrome(LBH-Z23281);Chunhui Plan of the Ministry of Education: Study on the Mechanism of the Tongdu YuPi Tiaoshen Acupuncture in Improving Hippocampal Synaptic Plasticity of Chronic Fatigue Syndrome Cognitive Impairment(HZKY20220308-202201357);Youth Talent Support Project of the Heilongjiang Provincial Association of Traditional Chinese Medicine: Study on the Effect and Mechanism of Tongdu Yupi Tiaoshen Acupuncture on Improving Hippocampal Synaptic Plasticity in Chronic Fatigue Syndrome Cognitive Impairment(2022-QNRC1-05);Research Project of Traditional Chinese Medicine in Heilongjiang Province: Study on the Mechanism of Acupuncture in Improving Hippocampal Synaptic Plasticity of Chronic Fatigue Syndrome Cognitive Impairment(ZHY2022-136)

Fold

Abstract

OBJECTIVE: To observe the effects of moxibustion at Zusanli (ST36) on rats with chronic fatigue syndrome (CFS) and to analyze the mechanisms of moxibustion through hippocampal Proteomics.
METHODS: Male Sprague-Dawley (SD) rats were randomly divided into three groups: control group (CON), model group (MOD), and moxibustion group (MOX), with 12 rats in each group. The MOD and MOX groups underwent chronic multi-factor stress stimulation for 35 d to establish the CFS model. After modeling, the rats in the MOX group received mild moxibustion at Zusanli (ST36) (bilateral) for 10 minutes daily for 28 d. During the treatment period, rats in both the MOD and MOX groups continued modeling, while the CON group was kept under normal breeding conditions. The general condition of the rats was monitored, and behaviors were assessed using the Open Field Test (OFT), Exhaustion Treadmill Test, and Morris Water Maze (MWM). Hematoxylin and eosin (HE) staining and transmission electron microscopy (TEM) were employed to observe morphological changes in the hippocampus. Label-free Proteomics were utilized to identify differentially expressed proteins (DEPs) in the hippocampus, followed by bioinformatics analysis. The reliability of the Proteomics results was verified using Parallel Reaction Monitoring.
RESULTS: A: Moxibustion at Zusanli (ST36) significantly reduced the general condition score of CFS rats, improved their behavioral performance in OFT, treadmill and MWM, and repaired the pathological and synaptic structural damage in the hippocampus.B: We identified DEPs by applying a fold change threshold of 1.2 and a significance level of P < 0.05. In the comparison between the CON and the MOD, we identified a total of 72 DEPs (31 up-regulated and 41 down-regulated) associated with the development of CFS. In the comparison between the MOX and the MOD group, we identified a total of 103 DEPs (40 up-regulated and 63 down-regulated) related to the therapeutic effects of moxibustion. Gene Ontology (GO) enrichment analysis showed that CFS and moxibustion treatment were related to multiple biological processes, molecular functions, and cellular components. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that CFS pathogenesis was linked to base excision repair, steroid biosynthesis, and systemic lupus erythematosus, Furthermore, the treatment of CFS with moxibustion was relevant to terpenoid skeleton biosynthesis.C: Compared with the two comparison groups, we identified 16 potential biomarkers, noting that moxibustion reversed the up-regulation of 14 DEPs and the down-regulation of 2 DEPs in CFS. These proteins are mainly associated with synaptic plasticity, ribosomal function, neurotransmitter secretion, glycine metabolism, and mitochondrial function.
CONCLUSION: Moxibustion at Zusanli (ST36) is effective in treating CFS, the potential biomarkers identified by Proteomics confirm that the mechanisms of moxibustion involve multiple targets and pathways, which may be key to regulating the structural and functional damage in the hippocampus associated with CFS, highlighting their significant value for future research.

Key words： moxibustion; point ST36 (Zusanli); fatigue syndrome, chronic; proteomics; computational biology

Cite this article

Chuwen FENG , Chaoran LI , Yan Yang , Yuanyuan QU , Zhongren SUN , Weibo SUN , Tingting LIU , Shulin LI , Tiansong Yang . Identifying potential biomarkers in the hippocampus of chronic fatigue syndrome rats treated with moxibustion at Zusanli (ST36): a proteomics study[J]. Journal of Traditional Chinese Medicine, 2025 , 45(3) : 571 -585 . DOI: 10.19852/j.cnki.jtcm.2025.03.012

References

1. Chronic COTD, Syndrome F, Populations BOTH, Medicine IO. Beyond myalgic encephalomyelitis/chronic fatigue syndrome:redefining an illness. Washington (DC): National Academies Press (US), 2015: 209-30.
2. Lim EJ, Son CG. Review of case definitions for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). J Transl Med 2020; 18: 289.
3. Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management. London: National Institute for Health and Care Excellence (NICE), 2021: 15.
4. Grach SL, Seltzer J, Chon TY, Ganesh R. Diagnosis and management of myalgic encephalomyelitis/chronic fatigue syndrome. Mayo Clin Proc 2023; 98: 1544-51.
5. Liu TT, Sun WB, Guo SH, et al. Research progress on pathogenesis of chronic fatigue syndrome and treatment of Traditional Chinese and Western Medicine. Auton Neurosci 2024; 255: 103198.
6. Arron HE, Marsh BD, Kell DB, Khan MA, Jaeger BR, Pretorius E. Myalgic encephalomyelitis/chronic fatigue syndrome: the biology of a neglected disease. Front Immunol 2024; 15: 1386607.
7. White P, Abbey S, Angus B, et al. Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis. J Neurol Neurosurg Psychiatry 2023; 94: 1056-63.
8. Wong TL, Weitzer DJ. Long covid and myalgic encephalomyelitis/chronic fatigue syndrome (me/cfs)-a systemic review and comparison of clinical presentation and symptomatology. Medicina (Kaunas) 2021; 57: 418.
9. Sukocheva OA, Maksoud R, Beeraka NM, et al. Analysis of post COVID-19 condition and its overlap with myalgic encephalomyelitis/chronic fatigue syndrome. J Adv Res 2022; 40: 179-96.
10. Komaroff AL, Bateman L. Will covid-19 lead to myalgic encephalomyelitis/chronic fatigue syndrome? Front Med (Lausanne) 2021; 7: 606824.
11. Komaroff AL, Lipkin WI. Insights from myalgic encephalomyelitis/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome. Trends Mol Med 2021; 27: 895-906.
12. Friedman KJ, Murovska M, Pheby D, Zalewski P. Our evolving understanding of ME/CFS. Medicina (Kaunas) 2021; 57: 200.
13. Mantovani E, Mariotto S, Gabbiani D, et al. Chronic fatigue syndrome: an emerging sequela in COVID-19 survivors? J Neurovirol 2021; 27: 631-7.
14. Bonilla H, Quach TC, Tiwari A, et al. Myalgic encephalomyelitis/chronic fatigue syndrome is common in post-acute sequelae of SARS-CoV-2 infection (PASC): results from a post-COVID-19 multidisciplinary clinic. Front Neurol 2023; 14: 1090747.
15. Fang Y, Yue BW, Ma HB, Yuan YP. Acupuncture and moxibustion for chronic fatigue syndrome: a systematic review and network Meta-analysis. Medicine (Baltimore) 2022; 101: e29310.
16. Zhang ML, Fu HJ, Tang Y, Luo ZG, Li JY, Li R. Effect of acupoint catgut embedding in chronic fatigue syndrome patients: a protocol for systematic review and Meta-analysis. Medicine (Baltimore) 2021; 100: e23946.
17. You JY, Ye J, Li HY, Ye WG, Hong ES. Moxibustion for chronic fatigue syndrome: a systematic review and Meta-analysis. Evid Based Complement Alternat Med 2021; 2021: 6418217.
18. Xue KY, Wang YP, Wang XZ, et al. The efficacy and safety of moxibustion for chronic fatigue syndrome: a protocol for systematic review and Meta-analysis. Medicine (Baltimore) 2021; 100: e25742.
19. Yin ZH, Wang LJ, Cheng Y, et al. Acupuncture for chronic fatigue syndrome: an overview of systematic reviews. Chin J Integr Med 2021; 27: 940-6.
20. Li CR, Yang Y, Feng CW, et al. Integrated 'omics analysis for the gut microbiota response to moxibustion in a rat model of chronic fatigue syndrome. J Tradit Chin Med 2023; 43: 1176-89.
21. Li CR, Wang X, Feng CW, et al. Improvement effects of moxibustion on intestinal mucosal barrier and fatigue of rats with chronic fatigue syndrome. Zhong Guo Zhong Yi Yao Ke Ji 2022; 29: 523-27.
22. Feng CW, Qu YY, Sun ZR, et al. Research progresses of MRI on brain structures and functions of chronic fatigue syndrome. Zhong Guo Yi Xue Ying Xiang Ji Shu 2022; 38: 775-8.
23. Maksoud R, du Preez S, Eaton-Fitch N, et al. A systematic review of neurological impairments in myalgic encephalomyelitis/ chronic fatigue syndrome using neuroimaging techniques. PLoS One 2020; 15: e232475.
24. Zeng XX, Feng CW, Zhang MH, Cheng WP, Sun Z, Yang TS. Exploring the central mechanism of mind-regulation electroacupuncture in treatment of chronic fatigue syndrome with anxiety and depression comorbidity based on functional magnetic resonance imaging. Zhong Guo Zhen Jiu 2024; 44: 3-11.
25. Wang TG, Sun ZR, Wang J, et al. The ReHo of rs-fMRI features for chronic fatigue syndrome in medical students. Lin Chuang Fang She Xue Za Zhi 2024; 43: 129-34.
26. Germain A, Levine SM, Hanson MR. In-depth analysis of the plasma proteome in me/cfs exposes disrupted ephrin-eph and immune system signaling. Proteomes 2021; 9: 6.
27. Eguchi A, Fukuda S, Kuratsune H, et al. Identification of actin network proteins, talin-1 and filamin-A, in circulating extracellular vesicles as blood biomarkers for human myalgic encephalomyelitis/chronic fatigue syndrome. Brain Behav Immun 2020; 84: 106-14.
28. Nunes M, Vlok M, Proal A, Kell DB, Pretorius E. Data-independent LC-MS/MS analysis of ME/CFS plasma reveals a dysregulated coagulation system, endothelial dysfunction, downregulation of complement machinery. Cardiovasc Diabetol 2024; 23: 254.
29. Yang Y, Sun ZR, Li CR, et al. Effect of electroacupuncture on fecal metabolism in rats with chronic fatigue syndrome. Liaoning Zhong Yi Za Zhi 2024: 51: 187-92.
30. Yang Y, Sun ZR, Li CR, et al. Effect of electroacupuncture on expression of protein phosphorylation in hippocampus tissues of rats with chronic fatigue syndrome. Zhen Ci Yan Jiu 2024; 49: 594-603.
31. Chi AP, Kang CZ, Zhang Y, et al. Immunomodulating and antioxidant effects of polysaccharide conjugates from the fruits of Ziziphus Jujube on chronic fatigue syndrome rats. Carbohydr Polym 2015; 122: 189-96.
32. Chi AP, Zhang Y, Kang YJ, Shen ZM. Metabolic mechanism of a polysaccharide from Schisandra chinensis to relieve chronic fatigue syndrome. Int J Biol Macromol 2016; 93: 322-32.
33. Zhang LF. Experimental acupuncture science. Beijing: Chemical Industry Press, 2010: 219-20.
34. Gao HL, Wu YL, Zhu HM, et al. Establishment of animal model with chronic fatigue syndrome and its influence on functions of blood vessel endothelium. Zhong Guo Zhong Yi Ji Chu Yi Xue Za Zhi 2009; 15: 904-6.
35. Chiu JH. How does moxibustion possibly work? Evid Based Complement Alternat Med 2013; 2013: 198584.
36. Feng CW, Qu YY, Fan ZL, et al. Acupoints regularity of moxibustion treating CFS based on collection visualization analysis system. Zhen Jiu Lin Chuang Za Zhi 2021; 37: 43-51.
37. Xu Q, Lu CX, Wu HX, et al. Effect of mild moxibustion at 45℃ with different durations at "Zusanli" [Zusanli (ST36)] on the inflammatory factors in the abdominal aorta of hyperlipidemia rats. Zhen Ci Yan Jiu 2023; 48: 923-32.
38. Li LL, Su L, Hu MY, Zhang XY, Chen JX, Lu Y. Analysis of the effects of Shengyang Sanhuo decoction and its disassem-bled prescriptions on behavior and intestinal flora of mice with chronic fatigue syndrome. Beijing Zhong Yi Yao Da Xue Xue Bao 2021; 44: 908-16.
39. Zhang GL, Lu BF, Wang EH, et al. Panax ginseng improves physical recovery and energy utilization on chronic fatigue in rats through the PI3K/AKT/mTOR signalling pathway. Pharm Biol 2023; 61: 316-23.
40. Saury JM. The role of the hippocampus in the pathogenesis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Med Hypotheses 2016; 86: 30-8.
41. Cifani P, Kentsis A. High sensitivity quantitative proteomics using automated multidimensional nano-flow chromatography and accumulated ion monitoring on quadrupole-orbitrap-linear ion trap mass spectrometer. Mol Cell Proteomics 2017; 16: 2006-16.
42. Ch'Ng TH, DeSalvo M, Lin P, Vashisht A, Wohlschlegel JA, Martin KC. Cell biological mechanisms of activity-dependent synapse to nucleus translocation of CRTC1 in neurons. Front Mol Neurosci 2015; 8: 48.
43. Ch'Ng TH, Uzgil B, Lin P, Avliyakulov NK, O'Dell TJ, Martin KC. Activity-dependent transport of the transcriptional coactivator CRTC1 from synapse to nucleus. Cell 2012; 150: 207-21.
44. Pan Y, He XZ, Li CC, et al. Neuronal activity recruits the CRTC1/CREB axis to drive transcription-dependent autophagy for maintaining late-phase LTD. Cell Rep 2021; 36: 109398.
45. Si YF, Xue X, Liu S, et al. CRTC1 signaling involvement in depression-like behavior of prenatally stressed offspring rat. Behav Brain Res 2021; 399: 113000.
46. Yan PY, Xue ZC, Li DZ, et al. Dysregulated CRTC1-BDNF signaling pathway in the hippocampus contributes to Abeta oligomer-induced long-term synaptic plasticity and memory impairment. Exp Neurol 2021; 345: 113812.
47. Turi Z, Lacey M, Mistrik M, Moudry P. Impaired ribosome biogenesis: mechanisms and relevance to cancer and aging. Aging (Albany NY) 2019; 11: 2512-40.
48. Graber TE, Hebert-Seropian S, Khoutorsky A, et al. Reactivation of stalled polyribosomes in synaptic plasticity. Proc Natl Acad Sci USA 2013; 110: 16205-10.
49. Tye BW, Commins N, Ryazanova Lyu, et al. Proteotoxicity from aberrant ribosome biogenesis compromises cell fitness. Elife 2019; 8: e43002.
50. Bouhours B, Gjoni E, Kochubey O, Schneggenburger R. Synaptotagmin2 (Syt2) drives fast release redundantly with Syt1 at the output synapses of parvalbumin-expressing inhibitory neurons. J Neurosci 2017; 37: 4604-17.
51. Lee J, Guan Z, Akbergenova Y, Littleton JT. Genetic analysis of synaptotagmin C2 domain specificity in regulating spontaneous and evoked neurotransmitter release. J Neurosci 2013; 33: 187-200.
52. Donkervoort S, Mohassel P, Laugwitz L, et al. Biallelic loss of function variants in SYT2 cause a treatable congenital onset presynaptic myasthenic syndrome. Am J Med Genet a 2020; 182: 2272-83.
53. Kochubey O, Lou X, Schneggenburger R. Regulation of transmitter release by Ca(2+) and synaptotagmin: insights from a large CNS synapse. Trends Neurosci 2011; 34: 237-46.
54. Bereczki E, Branca RM, Francis PT, et al. Synaptic markers of cognitive decline in neurodegenerative diseases: a proteomic approach. Brain 2018; 141: 582-95.
55. Yi XX, Li JY, Tang ZZ, et al. Marinoid J, a phenylglycoside from Avicennia marina fruit, ameliorates cognitive impairment in rat vascular dementia: a quantitative iTRAQ proteomic study. Pharm Biol 2020; 58: 1211-20.
56. Chaki SP, Rivera GM. Integration of signaling and cytoskeletal remodeling by Nck in directional cell migration. Bioarchitecture 2013; 3: 57-63.
57. Lettau M, Kliche S, Kabelitz D, Janssen O. The adapter proteins ADAP and Nck cooperate in T cell adhesion. Mol Immunol 2014; 60: 72-9.
58. Dubrac A, Genet G, Ola R, et al. Targeting NCK-mediated endothelial cell front-rear polarity inhibits neovascularization. Circulation 2016; 133: 409-21.
59. Srivastava N, Robichaux MA, Chenaux G, Henkemeyer M, Cowan CW. EphB2 receptor forward signaling controls cortical growth cone collapse via Nck and Pak. Mol Cell Neurosci 2013; 52: 106-16.
60. Thevenot E, Moreau AW, Rousseau V, et al. p21-Activated kinase 3 (PAK3) protein regulates synaptic transmission through its interaction with the Nck2/Grb4 protein adaptor. J Biol Chem 2011; 286: 40044-59.
61. Round JE, Sun H. The adaptor protein Nck2 mediates Slit1-induced changes in cortical neuron morphology. Mol Cell Neurosci 2011; 47: 265-73.
62. Chang CJ, Chang MY, Lee YC, et al. Nck2 is essential for limb trajectory selection by spinal motor axons. Dev Dyn 2018; 247: 1043-56.
63. Wegmeyer H, Egea J, Rabe N, et al. EphA4-dependent axon guidance is mediated by the RacGAP alpha2-chimaerin. Neuron 2007; 55: 756-67.
64. Lu YL, Liu YJ, McCoy MJ, Yoo AS. MiR-124 synergism with ELAVL3 enhances target gene expression to promote neuronal maturity. Proc Natl Acad Sci USA 2021; 118: e2015454118.
65. DeStefano AL, Latourelle J, Lew MF, et al. Replication of association between ELAVL4 and Parkinson disease: the GenePD study. Hum Genet 2008; 124: 95-9.
66. Krach F, Batra R, Wheeler EC, et al. Transcriptome-pathology correlation identifies interplay between TDP-43 and the expression of its kinase CK1E in sporadic ALS. Acta Neuropathol 2018; 136: 405-23.
67. Amadio M, Pascale A, Wang J, et al. nELAV proteins alteration in Alzheimer's disease brain: a novel putative target for amyloid-beta reverberating on Abeta PP processing. J Alzheimers Dis 2009; 16: 409-19.
68. Ogawa Y, Kakumoto K, Yoshida T, et al. Elavl3 is essential for the maintenance of Purkinje neuron axons. Sci Rep 2018; 8: 2722.
69. Leung KY, De Castro S, Galea GL, Copp AJ, Greene N. Glycine cleavage system H protein is essential for embryonic viability, implying additional function beyond the glycine cleavage system. Front Genet 2021; 12: 625120.
70. Adamus A, Muller P, Nissen B, et al. GCSH antisense regulation determines breast cancer cells' viability. Sci Rep 2018; 8: 15399.
71. Tifoun N, Bekhouche M, De Las HJ, et al. A high-throughput search for SFXN1 physical partners led to the identification of ATAD3, HSD10 and TIM50. Biology (Basel) 2022; 11: 1298.
72. Li YJ, Yang WK, Liu CJ, et al. SFXN1-mediated immune cell infiltration and tumorigenesis in lung adenocarcinoma: a potential therapeutic target. Int Immunopharmacol 2024; 132: 111918.
73. Zhang YH, Liu XS, Gao Y, et al. SFXN1 as a potential diagnostic and prognostic biomarker of LUAD is associated with (18)F-FDG metabolic parameters. Lung Cancer 2024; 188: 107449.
74. Acoba MG, Alpergin E, Renuse S, et al. The mitochondrial carrier SFXN1 is critical for complex Ⅲ integrity and cellular metabolism. Cell Rep 2021; 34: 108869.
75. Ross SM. Mitochondria dysfunction and chronic fatigue syndrome. Holist Nurs Pract 2024; 38: 245-7.
76. Dasi F. Alpha-1 antitrypsin deficiency. Med Clin (Barc) 2024; 162: 336-42.
77. Torres-Duran M, Lopez-Campos JL, Barrecheguren M, et al. Alpha-1 antitrypsin deficiency: outstanding questions and future directions. Orphanet J Rare Dis 2018; 13: 114.
78. Peng SY, Xu JH, Pelkey KA, et al. Suppression of agrin-22 production and synaptic dysfunction in Cln1 (-/-) mice. Ann Clin Transl Neurol 2015; 2: 1085-104.
79. Sakamoto K, Ozaki T, Suzuki Y, Kadomatsu K. Type Ⅱa RPTPs and Glycans: roles in axon regeneration and synaptogenesis. Int J Mol Sci 2021; 22:5524.
80. Ma KG, Hu HB, Zhou JS, et al. Neuronal Glypican4 promotes mossy fiber sprouting through the mTOR pathway after pilocarpine-induced status epilepticus in mice. Exp Neurol 2022; 347: 113918.
81. Huang K, Park S. Heparan Sulfated Glypican-4 is released from astrocytes by proteolytic shedding and gpi-anchor cleavage mechanisms. eNeuro 2021; 8.
82. Dowling C, Allen NJ. Mice lacking Glypican 4 display juvenile hyperactivity and adult social interaction deficits. Brain Plast 2018; 4: 197-209.
Options
Outlines

/

〈 〉