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In vitro drug screening models derived from different PC12 cell lines for exploring Parkinson’s disease based on electrochemical signals of catecholamine neurotransmitters

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Abstract

Gold nanostructures and a Nafion modified screen-printed carbon electrode (Nafion/AuNS/SPCE) were developed to assess the cell viability of Parkinson’s disease (PD) cell models. The electrochemical measurement of cell viability was reflected by catecholamine neurotransmitter (represented by dopamine) secretion capacity, followed by a traditional tetrazolium-based colorimetric assay for confirmation. Due to the  capacity to synthesize, store, and release catecholamines as well as their unlimited homogeneous proliferation, and ease of manipulation, pheochromocytoma (PC12) cells were used for PD cell modeling. Commercial low-differentiated and highly-differentiated PC12 cells, and home-made nerve growth factor (NGF) induced low-differentiated PC12 cells (NGF-differentiated PC12 cells) were included in the modeling. This approach achieved sensitive and rapid determination of cellular modeling and intervention states. Notably, among the three cell lines, NGF-differentiated PC12 cells displayed the enhanced neurotransmitter secretion level accompanied with attenuated growth rate, incremental dendrites in number and length that were highly resemble with neurons. Therefore, it was selected as the PD-tailorable modeling cell line. In short, the electrochemical sensor can be used to sensitively determine the biological function of neuron-like PC12 cells with negligible destruction and to explore the protective and regenerative impact of various substances on nerve cell model.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Greene LA, Tischler AS (1976) Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. P Nati Acad Sci USA 73(7):2424–2428. https://doi.org/10.1073/pnas.73.7.2424

    Article  CAS  ADS  Google Scholar 

  2. Vaudry D, Stork PJS, Lazarovici P, Eiden LE (2002) Signaling pathways for PC12 cell differentiation: making the right connections. Science 296(5573):1648–1649. https://doi.org/10.1126/science.1071552

    Article  CAS  PubMed  ADS  Google Scholar 

  3. Kongsamut S, Miller RJ (1986) Nerve growth factor modulates the drug sensitivity of neurotransmitter release from PC-12 cells. P Nati Acad Sci USA 83(7):2243–2247. https://doi.org/10.1073/pnas.83.7.2243

    Article  CAS  ADS  Google Scholar 

  4. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65(1–2):55–63. https://doi.org/10.1016/0022-1759(83)90303-4

    Article  CAS  PubMed  Google Scholar 

  5. Alley MC, Scudiero DA, Monks A, Hursey ML, Czerwinski MJ, Fine DL, Abbott BJ, Mayo JG, Shoemaker RH, Boyd MR (1988) Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res 48(3):589–601. https://aacrjournals.org/cancerres/article/48/3/589/493419

    CAS  PubMed  Google Scholar 

  6. Tominaga H, Ishiyama M, Ohseto F, Sasamoto K, Hamamoto T, Suzuki K, Watanabe M (1999) A water-soluble tetrazolium salt useful for colorimetric cell viability assay. Anal Commun 36(2):47–50. https://doi.org/10.1039/A809656B

    Article  CAS  Google Scholar 

  7. Yang XK, Tang Y, Qiu QF, Wu WT, Zhang FL, Liu YL, Huang WH (2019) Aβ1-42 oligomers induced a short-term increase of glutamate release prior to its depletion as measured by amperometry on single varicosities. Anal Chem 91(23):15123–15129. https://doi.org/10.1021/acs.analchem.9b03826

    Article  CAS  PubMed  Google Scholar 

  8. Wiatrak B, Kubis-Kubiak A, Piwowar A, Barg E (2020) PC12 cell line: cell types, coating of culture vessels, differentiation and other culture conditions. Cells 9(4):958. https://doi.org/10.3390/cells9040958

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Abe H, Ino K, Li CZ, Kanno Y, Inoue KY, Suda A, Kunikata R, Kunikata M, Takahashi Y, Shiku H, Matsue T (2015) Electrochemical imaging of dopamine release from three-dimensional-cultured PC12 cells using large-scale integration-based amperometric sensors. Anal Chem 87(12):6364–6370. https://doi.org/10.1021/acs.analchem.5b01307

    Article  CAS  PubMed  Google Scholar 

  10. Xu T, Lu X, Peng D, Wang G, Chen C, Liu W, Wu W, Mason TJ (2020) Ultrasonic stimulation of the brain to enhance the release of dopamine-A potential novel treatment for Parkinson’s disease. Ultrason Sonochem 63:104955. https://doi.org/10.1016/j.ultsonch.2019.104955

    Article  CAS  PubMed  Google Scholar 

  11. Liu L, Yang S, Wang H (2021) α-Lipoic acid alleviates ferroptosis in the MPP+-induced PC12 cells via activating the PI3K/Akt/Nrf2 pathway. Cell Biol Int 45(2):422–431. https://doi.org/10.1002/cbin.11505

    Article  CAS  PubMed  Google Scholar 

  12. Liu MM, Zhang FF, Liu H, Wu MJ, Liu ZJ, Huang PF (2023) Cell viability and drug evaluation biosensing system based on disposable AuNS/MWCNT nanocomposite modified screen-printed electrode for exocytosis dopamine detection. Talanta 254:124118. https://doi.org/10.1016/j.talanta.2022.124118

    Article  CAS  PubMed  Google Scholar 

  13. Zhang X, Wang Y, Zhang K, Sheng H, Wu Y, Wu H, Wang Y, Guan J, Meng Q, Li H, Li Z, Fan G, Wang Y (2021) Discovery of tetrahydropalmatine and protopine regulate the expression of dopamine receptor D2 to alleviate migraine from Yuanhu Zhitong formula. Phytomedicine 91:153702. https://doi.org/10.1016/j.phymed.2021.153702

    Article  CAS  PubMed  Google Scholar 

  14. Baronio D, Chen YC, Decker AR, Enckell L, B. Fernández-López B, Semenova S, Puttonen HAJ, Cornell RA, Panula P, (2022) Vesicular monoamine transporter 2 (SLC18A2) regulates monoamine turnover and brain development in zebrafish. Acta Physiol 234(1):e13725. https://doi.org/10.1111/apha.13725

    Article  CAS  Google Scholar 

  15. Liu JL, Zhang JQ, Zhou Y, Xiao DR, Zhuo Y, Chai YQ, Yuan R (2021) Crystallization-induced enhanced electrochemiluminescence from tetraphenyl alkene nanocrystals for ultrasensitive sensing. Anal Chem 93(31):10890–10897. https://doi.org/10.1021/acs.analchem.1c01258

    Article  CAS  PubMed  Google Scholar 

  16. Yu L, Feng L, Xiong L, Li S, Xu Q, Pan X, Xiao Y (2021) Multifunctional nanoscale lanthanide metal-organic framework based ratiometric fluorescence paper microchip for visual dopamine assay. Nanoscale 13(25):11188–11196. https://doi.org/10.1039/D1NR02036F

    Article  CAS  PubMed  Google Scholar 

  17. Shin M, Wang Y, Borgus JR, Venton BJ (2019) Electrochemistry at the synapse. Annu Rev Anal Chem 12:297–321. https://doi.org/10.1146/annurev-anchem-061318-115434

    Article  CAS  Google Scholar 

  18. Kokulnathan T, Ahmed F, Chen SM, Chen TW, Hasan PMZ, Bilgrami AL, Darwesh R (2021) Rational confinement of yttrium vanadate within three-dimensional graphene aerogel: electrochemical analysis of monoamine neurotransmitter (dopamine). ACS Appl Mater Inter 13(9):10987–10995. https://doi.org/10.1021/acsami.0c22781

    Article  CAS  Google Scholar 

  19. Malekzad H, Sahandi Zangabad P, Mirshekari H, Karimi M, Hamblin MR (2017) Noble metal nanoparticles in sensors: recent studies and applications. Nanotechnol Rev 6(3):301–329. https://doi.org/10.1515/ntrev-2016-0014

    Article  CAS  PubMed  Google Scholar 

  20. Greene LA, Tischler AS (1982) PC12 pheochromocytoma cultures in neurobiological research. In: Fedoroff S (ed) Advances in cellular neurobiology. Academic Press, Salt Lake, pp 373–414

    Google Scholar 

  21. Das KP, Freudenrich TM, Mundy WR (2004) Assessment of PC12 cell differentiation and neurite growth: a comparison of morphological and neurochemical measures. Neurotoxicol Teratol 26(3):397–406. https://doi.org/10.1016/j.ntt.2004.02.006

    Article  CAS  PubMed  Google Scholar 

  22. Jeon CY, Jin JK, Koh YH, Chun W, Choi IG, Kown HJ, Kim YS, Park JB (2010) Neurites from PC12 cells are connected to each other by synapse-like structures. Synapse 64(10):765–772. https://doi.org/10.1002/syn.20789

    Article  CAS  PubMed  Google Scholar 

  23. Lin YC, Koleske AJ (2010) Mechanisms of synapse and dendrite maintenance and their disruption in psychiatric and neurodegenerative disorders. Annu Rev Neurosci 33:49–378. https://doi.org/10.1146/annurev-neuro-060909-153204

    Article  CAS  Google Scholar 

  24. Dong H, Zhang J, Rong H, Zhang X, Dong M (2021) Paeoniflorin and plycyrrhetinic acid synergistically alleviate MPP+/MPTP-induced oxidative stress through Nrf2-dependent glutathione biosynthesis mechanisms. ACS Chem Neurosci 12(7):1100–1111. https://doi.org/10.1021/acschemneuro.0c00544

    Article  CAS  PubMed  Google Scholar 

  25. Biswas SC, Ryu E, Park C, Malagelada C, Greene LA (2005) Puma and p53 play required roles in death evoked in a cellular model of Parkinson disease. Neurochem Res 30:839–845. https://doi.org/10.1007/s11064-005-6877-5

    Article  CAS  PubMed  Google Scholar 

  26. González-Polo RA, Soler G, Fuentes JM (2004) MPP+ mechanism for its toxicity in cerebellar granule cells. Mol Neurobiol 30:253–264. https://doi.org/10.1385/MN:30:3:253

    Article  PubMed  Google Scholar 

  27. Carvey PM, Pieri S, Ling ZD (1997) Attenuation of levodopa-induced toxicity in mesencephalic cultures by pramipexole. J Neural Transm 104:209–228. https://doi.org/10.1007/BF01273182

    Article  CAS  PubMed  Google Scholar 

  28. Bolognin S, Fossépré M, Qing X, Jarazo J, Ščančar J, Moreno EL, Nickels SL, Wasner K, Ouzren N, Walter J, Grünewald A, Glaab E, Salamanca L, Fleming RMT, Antony PMA, Schwamborn JC (2019) 3D cultures of Parkinson’s disease-specific dopaminergic neurons for high content phenotyping and drug testing. Adv Sci 6(1):1800927. https://doi.org/10.1002/advs.201800927

    Article  CAS  Google Scholar 

  29. Luo Y, Qiu W, Wu B, Fang F (2022) An overview of mesenchymal stem cell-based therapy mediated by noncoding RNAs in the treatment of neurodegenerative diseases. Stem Cell Rev 18:457–473. https://doi.org/10.1007/s12015-021-10206-x

    Article  Google Scholar 

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Acknowledgements

The authors gratefully acknowledge the financial support of the National Natural Science Foundation of China (82373838) and Joint Funds for the Innovation of Science and Technology, Fujian Province (2020Y9009).

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Authors and Affiliations

  1. Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, China

    Yu Zhong, Meng-Meng Liu, Ji-Cheng Li, Tai-Cheng Lu, Xia Cao, Yuan-Jie Yang, Yun Lei & Ai-Lin Liu

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  1. Yu Zhong
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  2. Meng-Meng Liu
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Contributions

Yu Zhong: investigation, data curation, writing—original draft, writing—review and editing; Meng-Meng Liu: investigation, writing—original draft; Ji-Cheng Li, Tai-Cheng Lu, Xia Cao, and Yuan-Jie Yang: investigation; Yun Lei and Ai-Lin Liu: conceptualization, supervision, project administration, funding acquisition, writing—review and editing.

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Correspondence to Yun Lei or Ai-Lin Liu.

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Zhong, Y., Liu, MM., Li, JC. et al. In vitro drug screening models derived from different PC12 cell lines for exploring Parkinson’s disease based on electrochemical signals of catecholamine neurotransmitters. Microchim Acta 191, 170 (2024). https://doi.org/10.1007/s00604-024-06250-2

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