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Ciliary neurotrophic factor activation of astrocytes mediates neuronal damage via the IL‑6/IL‑6R pathway

  • Authors:
    • Hong-Tao Wang
    • Si-Tong Lu
    • Zhi-Hui Xia
    • Tao Xu
    • Wei-Yan Zou
    • Mei-Qun Sun
  • View Affiliations / Copyright

    Affiliations: Anhui Province Key Laboratory of Immunology in Chronic Diseases, Bengbu Medical University, Bengbu, Anhui 233030, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 32
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    Published online on: November 18, 2024
       https://doi.org/10.3892/mmr.2024.13396
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Abstract

The occurrence of epilepsy is a spontaneous and recurring process due to abnormal neuronal firing in the brain. Epilepsy is understood to be caused by an imbalance between excitatory and inhibitory neurotransmitters in the neural network. The close association between astrocytes and synapses can regulate the excitability of neurons through the clearance of neurotransmitters. Therefore, the abnormal function of astrocytes can lead to the onset and development of epilepsy. The onset of epilepsy can produce a large number of inflammatory mediators, which can aggravate epileptic seizures, leading to a vicious cycle. Neurons and glial cells interact to promote the onset and maintenance of epilepsy, but the specific underlying molecular mechanisms need to be further studied. Ciliary neurotrophic factor (CNTF) belongs to the IL‑6 cytokine family and is mainly secreted by astrocytes and Schwann cells. In the normal physiological state, CNTF levels are low, but in an epileptic state, CNTF levels in the serum and tears of patients are elevated. Astrocyte activation plays an important role in epileptic seizures. CNTF activates astrocytes to produce a variety of secreted proteins, which are secreted into the astrocyte culture medium (ACM), thus forming a distinct culture medium (CNTF‑ACM) that can be used to study the effect of astrocytes on neurons in vitro. CNTF‑activated astrocytes increase the secretion of the pro‑inflammatory factor IL‑6. In the present study, CNTF‑ACM was applied to primary cerebral cortical neurons to observe the specific effects of IL‑6 in CNTF‑ACM on neuronal activity and excitability. The results suggested that CNTF‑ACM can reduce neuronal activity via the IL‑6/IL‑6R pathway, promote neuronal apoptosis, increase Ca2+ inflow, activate the large conductance calcium‑activated potassium channel and enhance neuronal excitability. The results of the present study further revealed the functional changes of astrocytes after CNTF activated astrocytes and the effects on neuronal activity and excitability, thereby providing new experimental evidence for the role of communication between astrocytes and neurons in the mechanism of epileptic seizures.
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View References

1 

Vezzani A, French J, Bartfai T and Baram TZ: The role of inflammation in epilepsy. Nat Rev Neurol. 7:31–40. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Herrera G, Silvero CMJ, Becerra MC, Lasaga M and Scimonelli T: Modulatory role of α-MSH in hippocampal-dependent memory impairment, synaptic plasticity changes, oxidative stress, and astrocyte reactivity induced by short-term high-fat diet intake. Neuropharmacology. 239:1096882023. View Article : Google Scholar : PubMed/NCBI

3 

Zhang T, Liang W, Ou W, Zhang M, Cui S and Zhang S: Daphnetin alleviates neuropathic pain in chronic constrictive injury rats via regulating the NF-κB dependent CXCL1/CXCR2 signaling pathway. Pharm Biol. 61:746–754. 2023. View Article : Google Scholar : PubMed/NCBI

4 

Lovotti M, Mangan MSJ, McManus RM, Shkarina K, Vasconcelos MB and Latz E: Monitoring of inflammasome activation of macrophages and microglia in vitro, part 2: Assessing inflammasome activation. Methods Mol Biol. 2713:431–451. 2024. View Article : Google Scholar : PubMed/NCBI

5 

Richardson PM: Ciliary neurotrophic factor: A review. Pharmacol Ther. 63:187–198. 1994. View Article : Google Scholar : PubMed/NCBI

6 

Kang SS, Keasey MP, Cai J and Hagg T: Loss of neuron-astroglial interaction rapidly induces protective CNTF expression after stroke in mice. J Neurosci. 32:9277–9287. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Moradi P, Ganjkhani M, Anarkooli IJ and Abdanipour A: Neuroprotective effects of lovastatin in the pilocarpine rat model of epilepsy according to the expression of neurotrophic factors. Metab Brain Dis. 34:1061–1069. 2019. View Article : Google Scholar : PubMed/NCBI

8 

Shpak A, Guekht A, Druzhkova T, Rider F, Gudkova A and Gulyaeva N: Increased ciliary neurotrophic factor in blood serum and lacrimal fluid as a potential biomarkers of focal epilepsy. Neurol Sci. 43:493–498. 2022. View Article : Google Scholar : PubMed/NCBI

9 

Bechstein M, Häussler U, Neef M, Hofmann HD, Kirsch M and Haas CA: CNTF-mediated preactivation of astrocytes attenuates neuronal damage and epileptiform activity in experimental epilepsy. Exp Neurol. 236:141–150. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Jones SA and Jenkins BJ: Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer. Nat Rev Immunol. 18:773–789. 2018. View Article : Google Scholar : PubMed/NCBI

11 

Liang W, Wang J, Sui J, Yun F, Shen Y, Zhou J, Wu Y, Shen D and Zhang Q: Inflammation as a target for the treatment of fever-associated epilepsy in zebrafish larvae. Int Immunopharmacol. 116:1098022023. View Article : Google Scholar : PubMed/NCBI

12 

Hou X, Xiao S and Xu X, Qin M, Cheng X and Xu X: Glycoprotein non-metastatic melanoma protein B (GPNMB) protects against neuroinflammation and neuronal loss in pilocarpine-induced epilepsy via the regulation of microglial polarization. Neuroscience. 551:166–176. 2024. View Article : Google Scholar : PubMed/NCBI

13 

Ahmad SR, Zeyaullah M, AlShahrani AM, Dawria A, Ali H, Mohieldin A, Altijani AA, Razi U, Mehdi M, Akram S and Hussain ER: Deciphering the enigma of neuron-glial interactions in neurological disorders. Front Biosci (Landmark Ed). 29:1422024. View Article : Google Scholar : PubMed/NCBI

14 

Kahn MA, Ellison JA, Speight GJ and de Vellis J: CNTF regulation of astrogliosis and the activation of microglia in the developing rat central nervous system. Brain Res. 685:55–67. 1995. View Article : Google Scholar : PubMed/NCBI

15 

Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, Bennett ML, Münch AE, Chung WS, Peterson TC, et al: Neurotoxic reactive astrocytes are induced by activated microglia. Nature. 541:481–487. 2017. View Article : Google Scholar : PubMed/NCBI

16 

Ceyzériat K, Nicolaides A, Amossé Q, Fossey C, Cailly T, Fabis F, Garibotto V, Escartin C, Tournier BB and Millet P: Reactive astrocytes mediate TSPO overexpression in response to sustained CNTF exposure in the rat striatum. Mol Brain. 16:572023. View Article : Google Scholar : PubMed/NCBI

17 

Rohani R, Aliaghaei A, Abdollahifar MA, Sadeghi Y, Zare L, Dehghan S and Heidari MH: Long-Term effects of hippocampal low-frequency stimulation on pro-inflammatory factors and astrocytes activity in kindled rats. Cell J. 23:85–92. 2021.PubMed/NCBI

18 

Leo A, Nesci V, Tallarico M, Amodio N, Gallo Cantafio EM, De Sarro G, Constanti A, Russo E and Citraro R: IL-6 Receptor Blockade by Tocilizumab Has Anti-absence and Anti-epileptogenic Effects in the WAG/Rij Rat Model of Absence Epilepsy. Neurotherapeutics. 17:2004–2014. 2020. View Article : Google Scholar : PubMed/NCBI

19 

Uludag IF, Duksal T, Tiftikcioglu BI, Zorlu Y, Ozkaya F and Kirkali G: IL-1β, IL-6 and IL1Ra levels in temporal lobe epilepsy. Seizure. 26:22–25. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Uludag IF, Bilgin S, Zorlu Y, Tuna G and Kirkali G: Interleukin-6, interleukin-1 beta and interleukin-1 receptor antagonist levels in epileptic seizures. Seizure. 22:457–461. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Xiaoqin Z, Zhengli L, Changgeng Z, Xiaojing W and Li L: Changes in behavior and amino acid neurotransmitters in the brain of rats with seizure induced by IL-1beta or IL-6. J Huazhong Univ Sci Technolog Med Sci. 25:236–239. 2005.PubMed/NCBI

22 

Vezzani A, Balosso S and Ravizza T: The role of cytokines in the pathophysiology of epilepsy. Brain Behav Immun. 22:797–803. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Lu S, Wang J, Sun T, Yan H, Zou W, Li H, Qi Q and Sun M: IL-6 promotes the activation of rat astrocytes and down-regulation of the expression of Kir4.1 channel. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 38:316–320. 2022.(In Chinese). PubMed/NCBI

24 

Sun M, Liu H, Xu H, Wang H and Wang X: CNTF-Treated astrocyte conditioned medium enhances large-conductance calcium-activated potassium channel activity in rat cortical neurons. Neurochem Res. 41:1982–1992. 2016. View Article : Google Scholar : PubMed/NCBI

25 

Niesen CE, Xu J, Fan X, Li X, Wheeler CJ, Mamelak AN and Wang C: Transcriptomic profiling of human peritumoral neocortex tissues revealed genes possibly involved in tumor-induced epilepsy. PLoS One. 8:e560772013. View Article : Google Scholar : PubMed/NCBI

26 

Joseph DJ, Von Deimling M, Hasegawa Y, Cristancho AG, Ahrens-Nicklas RC, Rogers SL, Risbud R, McCoy AJ and Marsh ED: Postnatal Arx transcriptional activity regulates functional properties of PV interneurons. iScience. 24:1019992020. View Article : Google Scholar : PubMed/NCBI

27 

Guo Y, Nemeth J, O'Brien C, Susa M, Liu X, Zhang Z, Choy E, Mankin H, Hornicek F and Duan Z: Effects of siltuximab on the IL-6-induced signaling pathway in ovarian cancer. Clin Cancer Res. 16:5759–5769. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

29 

Zabrodskaya Y, Paramonova N, Litovchenko A, Bazhanova E, Gerasimov A, Sitovskaya D, Nezdorovina V, Kravtsova S, Malyshev S, Skiteva E and Samochernykh K: Neuroinflammatory dysfunction of the blood-brain barrier and basement membrane dysplasia play a role in the development of drug-resistant epilepsy. Int J Mol Sci. 24:126892023. View Article : Google Scholar : PubMed/NCBI

30 

Tan TH, Perucca P, O'Brien TJ, Kwan P and Monif M: Inflammation, ictogenesis, and epileptogenesis: An exploration through human disease. Epilepsia. 62:303–324. 2021. View Article : Google Scholar : PubMed/NCBI

31 

Purnell BS, Alves M and Boison D: Astrocyte-neuron circuits in epilepsy. Neurobiol Dis. 179:1060582023. View Article : Google Scholar : PubMed/NCBI

32 

Sun M, Liu H, Xu H, Wang H and Wang X: CNTF-ACM promotes mitochondrial respiration and oxidative stress in cortical neurons through upregulating L-type calcium channel activity. Mol Cell Biochem. 420:195–206. 2016. View Article : Google Scholar : PubMed/NCBI

33 

Escartin C, Brouillet E, Gubellini P, Trioulier Y, Jacquard C, Smadja C, Knott GW, Kerkerian-Le Goff L, Déglon N, Hantraye P and Bonvento G: Ciliary neurotrophic factor activates astrocytes, redistributes their glutamate transporters GLAST and GLT-1 to raft microdomains, and improves glutamate handling in vivo. J Neurosci. 26:5978–5989. 2006. View Article : Google Scholar : PubMed/NCBI

34 

Foiadelli T, Santangelo A, Costagliola G, Costa E, Scacciati M, Riva A, Volpedo G, Smaldone M, Bonuccelli A, Clemente AM, et al: Neuroinflammation and status epilepticus: A narrative review unraveling a complex interplay. Front Pediatr. 11:12519142023. View Article : Google Scholar : PubMed/NCBI

35 

Andrioli A, Fabene PF, Mudò G, Barresi V, Di Liberto V, Frinchi M, Bentivoglio M and Condorelli DF: Downregulation of the astroglial connexin expression and neurodegeneration after pilocarpine-induced status epilepticus. Int J Mol Sci. 24:232022. View Article : Google Scholar : PubMed/NCBI

36 

Çarçak N, Onat F and Sitnikova E: Astrocytes as a target for therapeutic strategies in epilepsy: current insights. Front Mol Neurosci. 16:11837752023. View Article : Google Scholar : PubMed/NCBI

37 

Hotz AL, Jamali A, Rieser NN, Niklaus S, Aydin E, Myren-Svelstad S, Lalla L, Jurisch-Yaksi N, Yaksi E and Neuhauss S: Loss of glutamate transporter eaat2a leads to aberrant neuronal excitability, recurrent epileptic seizures, and basal hypoactivity. Glia. 70:196–214. 2022. View Article : Google Scholar : PubMed/NCBI

38 

Bellot-Saez A, Kékesi O, Morley JW and Buskila Y: Astrocytic modulation of neuronal excitability through K(+) spatial buffering. Neurosci Biobehav Rev. 77:87–97. 2017. View Article : Google Scholar : PubMed/NCBI

39 

Zurolo E, de Groot M, Iyer A, Anink J, van Vliet EA, Heimans JJ, Reijneveld JC, Gorter JA and Aronica E: Regulation of Kir4.1 expression in astrocytes and astrocytic tumors: A role for interleukin-1 β. J Neuroinflammation. 9:2802012. View Article : Google Scholar : PubMed/NCBI

40 

Sun M, Wang H, Qi Q, Yan H, Zou W, Dong X, Wang Z, Wang J and Wang X: IL-1β promotes the proliferation of astrocytes and downregulates the expression of Kir4.1. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 33:446–449. 2017.(In Chinese). PubMed/NCBI

41 

Sun M, Yan H, Zou W, Wang Y, Li H and Wang X: Lipopolysaccharide induces astrocyte activation and downregulates the expression of Kir4.1 channel. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 32:196–200. 2016.(In Chinese). PubMed/NCBI

42 

Ma L, Wu Q, You Y, Zhang P, Tan D, Liang M, Huang Y, Gao Y, Ban Y, Chen Y and Yuan J: Neuronal small extracellular vesicles carrying miR-181c-5p contribute to the pathogenesis of epilepsy by regulating the protein kinase C-δ/glutamate transporter-1 axis in astrocytes. Glia. 72:1082–1095. 2024. View Article : Google Scholar : PubMed/NCBI

43 

Hazell AS, Rao KV, Danbolt NC, Pow DV and Butterworth RF: Selective down-regulation of the astrocyte glutamate transporters GLT-1 and GLAST within the medial thalamus in experimental Wernicke's encephalopathy. J Neurochem. 78:560–568. 2001. View Article : Google Scholar : PubMed/NCBI

44 

Rakhade SN and Loeb JA: Focal reduction of neuronal glutamate transporters in human neocortical epilepsy. Epilepsia. 49:226–236. 2008. View Article : Google Scholar : PubMed/NCBI

45 

Peterson AR, Garcia TA, Cullion K, Tiwari-Woodruff SK, Pedapati EV and Binder DK: Targeted overexpression of glutamate transporter-1 reduces seizures and attenuates pathological changes in a mouse model of epilepsy. Neurobiol Dis. 157:1054432021. View Article : Google Scholar : PubMed/NCBI

46 

Muñoz-Ballester C, Berthier A, Viana R and Sanz P: Homeostasis of the astrocytic glutamate transporter GLT-1 is altered in mouse models of Lafora disease. Biochim Biophys Acta. 1862:1074–1083. 2016. View Article : Google Scholar : PubMed/NCBI

47 

Mahmoud S, Gharagozloo M, Simard C and Gris D: Astrocytes maintain glutamate homeostasis in the CNS by controlling the balance between glutamate uptake and release. Cells. 8:1842019. View Article : Google Scholar : PubMed/NCBI

48 

Yang J, Vitery M, Chen J, Osei-Owusu J, Chu J and Qiu Z: Glutamate-Releasing SWELL1 channel in astrocytes modulates synaptic transmission and promotes brain damage in stroke. Neuron. 102:813–827.e6. 2019. View Article : Google Scholar : PubMed/NCBI

49 

Cao W, Xiong S, Ji W, Wei H, Ma F and Mao L: Neuroprotection Role of Vitamin C by Upregulating Glutamate Transporter-1 in Auditory Cortex of Noise-Induced Tinnitus Animal Model. ACS Chem Neurosci. 15:1197–1205. 2024. View Article : Google Scholar : PubMed/NCBI

50 

Skórkowska A, Krzyżanowska W, Bystrowska B, Torregrossa R, Whiteman M, Pomierny B and Budziszewska B: The Hydrogen Sulfide Donor AP39 reduces glutamate-mediated excitotoxicity in a rat model of brain ischemia. Neuroscience. 539:86–102. 2024. View Article : Google Scholar : PubMed/NCBI

51 

Hameed MQ, Hui B, Lin R, MacMullin PC, Pascual-Leone A, Vermudez SAD and Rotenberg A: Depressed glutamate transporter 1 expression in a mouse model of Dravet syndrome. Ann Clin Transl Neurol. 10:1695–1699. 2023. View Article : Google Scholar : PubMed/NCBI

52 

Mohamed AM, Ali DA, Kolieb E and Abdelaziz EZ: Ceftriaxone and selenium mitigate seizures and neuronal injury in pentylenetetrazole-kindled rats: Oxidative stress and inflammatory pathway. Int Immunopharmacol. 120:1103042023. View Article : Google Scholar : PubMed/NCBI

53 

Taspinar N, Hacimuftuoglu A, Butuner S, Togar B, Arslan G, Taghizadehghalehjoughi A, Okkay U, Agar E, Stephens R Jr, Turkez H and Abd El-Aty AM: Differential effects of inhibitors of PTZ-induced kindling on glutamate transporters and enzyme expression. Clin Exp Pharmacol Physiol. 48:1662–1673. 2021. View Article : Google Scholar : PubMed/NCBI

54 

Wallraff A, Köhling R, Heinemann U, Theis M, Willecke K and Steinhäuser C: The impact of astrocytic gap junctional coupling on potassium buffering in the hippocampus. J Neurosci. 26:5438–5447. 2006. View Article : Google Scholar : PubMed/NCBI

55 

Moraga-Amaro R, Jerez-Baraona JM, Simon F and Stehberg J: Role of astrocytes in memory and psychiatric disorders. J Physiol Paris. 108:240–251. 2014. View Article : Google Scholar : PubMed/NCBI

56 

Orellana JA and Stehberg J: Hemichannels: New roles in astroglial function. Front Physiol. 5:1932014. View Article : Google Scholar : PubMed/NCBI

57 

Bruzzone S, Guida L, Zocchi E, Franco L and De Flora A: Connexin 43 hemi channels mediate Ca2+-regulated transmembrane NAD+ fluxes in intact cells. FASEB J. 15:10–12. 2001. View Article : Google Scholar : PubMed/NCBI

58 

De Bock M, Wang N, Decrock E, Bultynck G and Leybaert L: Intracellular Cleavage of the Cx43 C-Terminal Domain by Matrix-Metalloproteases: A novel contributor to inflammation. Mediators Inflamm. 2015:2574712015. View Article : Google Scholar : PubMed/NCBI

59 

Bedner P and Steinhäuser C: Role of impaired astrocyte gap junction coupling in epileptogenesis. Cells. 12:16692023. View Article : Google Scholar : PubMed/NCBI

60 

Vizuete AFK, Leal MB, Moreira AP, Seady M, Taday J and Gonçalves CA: Arundic acid (ONO-2506) downregulates neuroinflammation and astrocyte dysfunction after status epilepticus in young rats induced by Li-pilocarpine. Prog Neuropsychopharmacol Biol Psychiatry. 123:1107042023. View Article : Google Scholar : PubMed/NCBI

61 

Liu B, Ran X, Yi Y, Zhang X, Chen H and Hu Y: Anticonvulsant effect of carbenoxolone on chronic epileptic rats and its mechanism related to connexin and high-frequency oscillations. Front Mol Neurosci. 15:8709472022. View Article : Google Scholar : PubMed/NCBI

62 

Elisevich K, Rempel SA, Smith BJ and Edvardsen K: Hippocampal connexin 43 expression in human complex partial seizure disorder. Exp Neurol. 145:154–164. 1997. View Article : Google Scholar : PubMed/NCBI

63 

Bedner P, Dupper A, Hüttmann K, Müller J, Herde MK, Dublin P, Deshpande T, Schramm J, Häussler U, Haas CA, et al: Astrocyte uncoupling as a cause of human temporal lobe epilepsy. Brain 138(Pt 5). 1208–1222. 2015.PubMed/NCBI

64 

Haghikia A, Ladage K, Hinkerohe D, Vollmar P, Heupel K, Dermietzel R and Faustmann PM: Implications of antiinflammatory properties of the anticonvulsant drug levetiracetam in astrocytes. J Neurosci Res. 86:1781–1788. 2008. View Article : Google Scholar : PubMed/NCBI

65 

Retamal MA, Froger N, Palacios-Prado N, Ezan P, Sáez PJ, Sáez JC and Giaume C: Cx43 hemichannels and gap junction channels in astrocytes are regulated oppositely by proinflammatory cytokines released from activated microglia. J Neurosci. 27:13781–13792. 2007. View Article : Google Scholar : PubMed/NCBI

66 

Sano F, Shigetomi E, Shinozaki Y, Tsuzukiyama H, Saito K, Mikoshiba K, Horiuchi H, Cheung DL, Nabekura J, Sugita K, et al: Reactive astrocyte-driven epileptogenesis is induced by microglia initially activated following status epilepticus. JCI Insight. 6:e1353912021. View Article : Google Scholar : PubMed/NCBI

67 

Li T, Lan JQ and Boison D: Uncoupling of astrogliosis from epileptogenesis in adenosine kinase (ADK) transgenic mice. Neuron Glia Biol. 4:91–99. 2008. View Article : Google Scholar : PubMed/NCBI

68 

Griffioen G: Calcium dyshomeostasis drives pathophysiology and neuronal demise in age-related neurodegenerative diseases. Int J Mol Sci. 24:132432023. View Article : Google Scholar : PubMed/NCBI

69 

Gola L, Bierhansl L, Csatári J, Schroeter CB, Korn L, Narayanan V, Cerina M, Abdolahi S, Speicher A, Hermann AM, et al: NOX4-derived ROS are neuroprotective by balancing intracellular calcium stores. Cell Mol Life Sci. 80:1272023. View Article : Google Scholar : PubMed/NCBI

70 

Cai Q and Jeong YY: Mitophagy in Alzheimer's disease and other age-related neurodegenerative diseases. Cells. 9:1502020. View Article : Google Scholar : PubMed/NCBI

71 

Petrosillo G, Ruggiero FM and Paradies G: Role of reactive oxygen species and cardiolipin in the release of cytochrome c from mitochondria. FASEB J. 17:2202–2208. 2003. View Article : Google Scholar : PubMed/NCBI

72 

Esteras N, Kopach O, Maiolino M, Lariccia V, Amoroso S, Qamar S, Wray S, Rusakov DA, Jaganjac M and Abramov AY: Mitochondrial ROS control neuronal excitability and cell fate in frontotemporal dementia. Alzheimers Dement. 18:318–338. 2022. View Article : Google Scholar : PubMed/NCBI

73 

Jung S, Chung Y, Lee Y, Lee Y, Cho JW, Shin EJ, Kim HC and Oh YJ: Buffering of cytosolic calcium plays a neuroprotective role by preserving the autophagy-lysosome pathway during MPP(+)-induced neuronal death. Cell Death Discov. 5:1302019. View Article : Google Scholar : PubMed/NCBI

74 

Park J, Jang KM and Park KK: Effects of Apamin on MPP(+)-Induced Calcium Overload and Neurotoxicity by Targeting CaMKII/ERK/p65/STAT3 signaling pathways in dopaminergic neuronal cells. Int J Mol Sci. 23:152552022. View Article : Google Scholar : PubMed/NCBI

75 

Stutzmann GE: The pathogenesis of Alzheimers disease is it a lifelong ‘calciumopathy’. Neuroscientist. 13:546–559. 2007. View Article : Google Scholar : PubMed/NCBI

76 

Hwang Y, Kim HC and Shin EJ: Enhanced neurogenesis is involved in neuroprotection provided by rottlerin against trimethyltin-induced delayed apoptotic neuronal damage. Life Sci. 262:1184942020. View Article : Google Scholar : PubMed/NCBI

77 

Schulien AJ, Justice JA, Di Maio R, Wills ZP, Shah NH and Aizenman E: Zn(2+)-induced Ca(2+) release via ryanodine receptors triggers calcineurin-dependent redistribution of cortical neuronal Kv2.1 K(+) channels. J Physiol. 594:2647–2659. 2016. View Article : Google Scholar : PubMed/NCBI

78 

Shah KR, Guan X and Yan J: Structural and functional coupling of calcium-activated BK channels and calcium-permeable channels within nanodomain signaling complexes. Front Physiol. 12:7965402022. View Article : Google Scholar : PubMed/NCBI

79 

Griguoli M, Sgritta M and Cherubini E: Presynaptic BK channels control transmitter release: Physiological relevance and potential therapeutic implications. J Physiol. 594:3489–3500. 2016. View Article : Google Scholar : PubMed/NCBI

80 

Sun AX, Yuan Q, Fukuda M, Yu W, Yan H, Lim G, Nai MH, D'Agostino GA, Tran HD, Itahana Y, et al: Potassium channel dysfunction in human neuronal models of Angelman syndrome. Science. 366:1486–1492. 2019. View Article : Google Scholar : PubMed/NCBI

81 

Du W, Bautista JF, Yang H, Diez-Sampedro A, You SA, Wang L, Kotagal P, Lüders HO, Shi J, Cui J, et al: Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder. Nat Genet. 37:733–738. 2005. View Article : Google Scholar : PubMed/NCBI

82 

Brenner R, Chen QH, Vilaythong A, Toney GM, Noebels JL and Aldrich RW: BK channel beta4 subunit reduces dentate gyrus excitability and protects against temporal lobe seizures. Nat Neurosci. 8:1752–1759. 2005. View Article : Google Scholar : PubMed/NCBI

83 

Shruti S, Clem RL and Barth AL: A seizure-induced gain-of-function in BK channels is associated with elevated firing activity in neocortical pyramidal neurons. Neurobiol Dis. 30:323–330. 2008. View Article : Google Scholar : PubMed/NCBI

84 

Benton MD, Lewis AH, Bant JS and Raman IM: Iberiotoxin-sensitive and -insensitive BK currents in Purkinje neuron somata. J Neurophysiol. 109:2528–2541. 2013. View Article : Google Scholar : PubMed/NCBI

85 

Song A, Wang J, Tong Y, Fang J, Zhang Y, Zhang H, Ruan H, Wang K and Liu Y: BKCa channels regulate the immunomodulatory properties of WJ-MSCs by affecting the exosome protein profiles during the inflammatory response. Stem Cell Res Ther. 11:4402020. View Article : Google Scholar : PubMed/NCBI

86 

Zhang X, Wang L, Xu L and Zou L: Effects of Atractylodes macrocephala on the cytomembrane Ca2+-activated K+ currents in cells of human pregnant myometrial smooth muscles. J Huazhong Univ Sci Technolog Med Sci. 28:200–203. 2008. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wang H, Lu S, Xia Z, Xu T, Zou W and Sun M: Ciliary neurotrophic factor activation of astrocytes mediates neuronal damage via the IL‑6/IL‑6R pathway. Mol Med Rep 31: 32, 2025.
APA
Wang, H., Lu, S., Xia, Z., Xu, T., Zou, W., & Sun, M. (2025). Ciliary neurotrophic factor activation of astrocytes mediates neuronal damage via the IL‑6/IL‑6R pathway. Molecular Medicine Reports, 31, 32. https://doi.org/10.3892/mmr.2024.13396
MLA
Wang, H., Lu, S., Xia, Z., Xu, T., Zou, W., Sun, M."Ciliary neurotrophic factor activation of astrocytes mediates neuronal damage via the IL‑6/IL‑6R pathway". Molecular Medicine Reports 31.2 (2025): 32.
Chicago
Wang, H., Lu, S., Xia, Z., Xu, T., Zou, W., Sun, M."Ciliary neurotrophic factor activation of astrocytes mediates neuronal damage via the IL‑6/IL‑6R pathway". Molecular Medicine Reports 31, no. 2 (2025): 32. https://doi.org/10.3892/mmr.2024.13396
Copy and paste a formatted citation
x
Spandidos Publications style
Wang H, Lu S, Xia Z, Xu T, Zou W and Sun M: Ciliary neurotrophic factor activation of astrocytes mediates neuronal damage via the IL‑6/IL‑6R pathway. Mol Med Rep 31: 32, 2025.
APA
Wang, H., Lu, S., Xia, Z., Xu, T., Zou, W., & Sun, M. (2025). Ciliary neurotrophic factor activation of astrocytes mediates neuronal damage via the IL‑6/IL‑6R pathway. Molecular Medicine Reports, 31, 32. https://doi.org/10.3892/mmr.2024.13396
MLA
Wang, H., Lu, S., Xia, Z., Xu, T., Zou, W., Sun, M."Ciliary neurotrophic factor activation of astrocytes mediates neuronal damage via the IL‑6/IL‑6R pathway". Molecular Medicine Reports 31.2 (2025): 32.
Chicago
Wang, H., Lu, S., Xia, Z., Xu, T., Zou, W., Sun, M."Ciliary neurotrophic factor activation of astrocytes mediates neuronal damage via the IL‑6/IL‑6R pathway". Molecular Medicine Reports 31, no. 2 (2025): 32. https://doi.org/10.3892/mmr.2024.13396
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