Skip to main content
Log in

Lipopolysaccharide-induced Trigeminal Ganglion Nerve Fiber Damage is Associated with Autophagy Inhibition

  • Published:
Current Medical Science Aims and scope Submit manuscript

Abstract

Objective

This study aimed to determine whether lipopolysaccharide (LPS) induces the loss of corneal nerve fibers in cultured trigeminal ganglion (TG) cells, and the underlying mechanism of LPS-induced TG neurite damage.

Methods

TG neurons were isolated from C57BL/6 mice, and the cell viability and purity were maintained for up to 7 days. Then, they were treated with LPS (1 µg/mL) or the autophagy regulator (autophibib and rapamycin) alone or in combination for 48 h, and the length of neurites in TG cells was examined by the immunofluorescence staining of the neuron-specific protein β3-tubulin. Afterwards, the molecular mechanisms by which LPS induces TG neuron damage were explored.

Results

The immunofluorescence staining revealed that the average length of neurites in TG cells significantly decreased after LPS treatment. Importantly, LPS induced the impairment of autophagic flux in TG cells, which was evidenced by the increase in the accumulation of LC3 and p62 proteins. The pharmacological inhibition of autophagy by autophinib dramatically reduced the length of TG neurites. However, the rapamycin-induced activation of autophagy significantly lessened the effect of LPS on the degeneration of TG neurites.

Conclusion

LPS-induced autophagy inhibition contributes to the loss of TG neurites.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Fakih D, Zhao Z, Nicolle P, et al. Chronic dry eye induced corneal hypersensitivity, neuroinflammatory responses, and synaptic plasticity in the mouse trigeminal brainstem. J Neuroinflammation, 2019,16(1):268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kishimoto Y, Yabuta C, Shearer TR, et al. FK962 promotes neurite elongation and regeneration of cultured rat trigeminal ganglion cells: possible involvement of GDNF. Invest Ophthalmol Vis Sci, 2012,53(9):5312–5319

    Article  CAS  PubMed  Google Scholar 

  3. Ohara K, Shimizu K, Matsuura S, et al. Toll-like receptor 4 signaling in trigeminal ganglion neurons contributes tongue-referred pain associated with tooth pulp inflammation. J Neuroinflammation, 2013,10:139

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kunda PE, Cavicchia JC, Acosta CG. Lipopolysaccharides and trophic factors regulate the LPS receptor complex in nodose and trigeminal neurons. Neuroscience, 2014,280:60–72

    Article  CAS  PubMed  Google Scholar 

  5. Chung MK, Lee J, Duraes G, et al. Lipopolysaccharide-induced pulpitis up-regulates TRPV1 in trigeminal ganglia. J Dent Res, 2011,90(9):1103–1107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Qin Y, Qiu J, Wang P, et al. Impaired autophagy in microglia aggravates dopaminergic neurodegeneration by regulating NLRP3 inflammasome activation in experimental models of Parkinson’s disease. Brain Behav Immun, 2021,91:324–338

    Article  CAS  PubMed  Google Scholar 

  7. Guo F, Liu X, Cai H, et al. Autophagy in neuro-degenerative diseases: pathogenesis and therapy. Brain Pathol, 2018,28(1):3–13

    Article  CAS  PubMed  Google Scholar 

  8. Hu J, Huang Y, Lin Y, et al. Protective effect inhibiting the expression of miR-181a on the diabetic corneal nerve in a mouse model. Exp Eye Res, 2020,192:107925

    Article  CAS  PubMed  Google Scholar 

  9. Lee JW, Nam H, Kim LE, et al. TLR4 (toll-like receptor 4) activation suppresses autophagy through inhibition of FOXO3 and impairs phagocytic capacity of microglia. Autophagy, 2019,15(5):753–770

    Article  CAS  PubMed  Google Scholar 

  10. Clarke JP, Mearow K. Autophagy inhibition in endogenous and nutrient-deprived conditions reduces dorsal root ganglia neuron survival and neurite growth in vitro. J Neurosci Res, 2016,94(7):653–670

    Article  CAS  PubMed  Google Scholar 

  11. Cho H, Jeon HJ, Park S, et al. Neurite growth of trigeminal ganglion neurons in vitro with near-infrared light irradiation. J Photochem Photobiol B, 2020,210:111959

    Article  CAS  PubMed  Google Scholar 

  12. Zhu Y, Liu Z, Peng YP, et al. Interleukin-10 inhibits neuroinflammation-mediated apoptosis of ventral mesencephalic neurons via JAK-STAT3 pathway. Int Immunopharmacol, 2017,50:353–360

    Article  CAS  PubMed  Google Scholar 

  13. Park T, Chen H, Kevala K, et al. N-Docosahexaenoy-lethanolamine ameliorates LPS-induced neuroinflammation via cAMP/PKA-dependent signaling. J Neuroinflammation, 2016,13(1):284

    Article  PubMed  PubMed Central  Google Scholar 

  14. Lynds R, Lyu C, Lyu GW, et al. Neuronal plasticity of trigeminal ganglia in mice following nerve injury. J Pain Res, 2017,10:349–357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Li M, Xin M, Song K, et al. Evaluation of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer nanomicelle for trigeminal ganglion neurons delivering with intranasal administration. Curr Eye Res, 2018,43(3):406–414

    Article  PubMed  Google Scholar 

  16. Cortina MS, He J, Russ T, et al. Neuroprotectin D1 restores corneal nerve integrity and function after damage from experimental surgery. Invest Ophthalmol Vis Sci, 2013,54(6):4109–4116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Nakajima E, Walkup RD, Shearer TR, et al. FK962 induces neurite outgrowth in cultured monkey trigeminal ganglion cells. Graefes Arch Clin Exp Ophthalmol, 2017,255(1):107–112

    Article  CAS  PubMed  Google Scholar 

  18. Kaewpitak A, Bauer CS, Seward EP, et al. Porphyromonas gingivalis lipopolysaccharide rapidly activates trigeminal sensory neurons and may contribute to pulpal pain. Int Endod J, 2020, 53(6):846–858

    Article  CAS  PubMed  Google Scholar 

  19. Iannotta M, Belardo C, Trotta MC, et al. N-palmitoyl-D-glucosamine, a Natural Monosaccharide-Based Glycolipid, Inhibits TLR4 and Prevents LPS-Induced Inflammation and Neuropathic Pain in Mice. Int J Mol Sci, 2021,22(3):1491

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hartmann H, Hoehne K, Rist E, et al. miR-124 disinhibits neurite outgrowth in an inflammatory environment. Cell Tissue Res, 2015,362(1):9–20

    Article  CAS  PubMed  Google Scholar 

  21. Inada T, Sato H, Hayashi Y, et al. Rapamycin Accelerates Axon Regeneration Through Schwann Cell-mediated Autophagy Following Inferior Alveolar Nerve Transection in Rats. Neuroscience, 2021,468:43–52

    Article  CAS  PubMed  Google Scholar 

  22. Yang Y, Fukui K, Koike T, et al. Induction of autophagy in neurite degeneration of mouse superior cervical ganglion neurons. Eur J Neurosci, 2007,26(10):2979–2988

    Article  PubMed  Google Scholar 

  23. Yang Y, Coleman M, Zhang L, et al. Autophagy in axonal and dendritic degeneration. Trends Neurosci, 2013,36(7):418–428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jing Du.

Additional information

Conflict of Interest Statement

No potential conflicts of interest were disclosed.

This work was supported by the Key Research and Development Program of Shaanxi Provice (No. 2023-YBSF-586), Natural Science Basic Research Plan of Shaanxi Province of China (No. 2017JM8043), the Health Research Project of Shaanxi Province (No. 2020yb11), and the Science Research of Xi’an Fourth Hospital of Shaanxi Province of China (No. FZ-4).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Y., Li, J., Wei, Ss. et al. Lipopolysaccharide-induced Trigeminal Ganglion Nerve Fiber Damage is Associated with Autophagy Inhibition. CURR MED SCI 43, 489–495 (2023). https://doi.org/10.1007/s11596-023-2739-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-023-2739-0

Key words

Navigation