DOI QR코드

DOI QR Code

The Protective Effects of IGF-1 on Different Subpopulations of DRG Neurons with Neurotoxicity Induced by gp120 and Dideoxycytidine In Vitro

  • Lu, Lin (Department of Neurology, Shandong University Affiliated Shandong Provincial Hospital) ;
  • Dong, Haixia (Department of Computer Tomography and Magnetic Resonance Imaging, Weifang Medical College Affiliated Yidu Central Hospital) ;
  • Liu, Guixiang (Department of Histology and Embryology, Binzhou Medical College) ;
  • Yuan, Bin (Department of Internal Medicine, Heze Boai Hospital) ;
  • Li, Yizhao (Jinan e-Join Science and Technology, Co., Ltd.) ;
  • Liu, Huaxiang (Department of Rheumatology, Shandong University Qilu Hospital)
  • Received : 2014.03.24
  • Accepted : 2014.07.26
  • Published : 2014.11.30

Abstract

Peripheral neuropathy induced by human immunodeficiency virus (HIV) infection and antiretroviral therapy is not only difficult to distinguish in clinical practice, but also difficult to relieve the pain symptoms by analgesics because of the severity of the disease at the later stage. Hence, to explore the mechanisms of HIV-related neuropathy and find new therapeutic options are particularly important for relieving neuropathic pain symptoms of the patients. In the present study, primary cultured embryonic rat dorsal root ganglion (DRG) neurons were used to determine the neurotoxic effects of HIV-gp120 protein and/or antiretroviral drug dideoxycytidine (ddC) and the therapeutic actions of insulin-like growth factor-1 (IGF-1) on gp120- or ddC-induced neurotoxicity. DRG neurons were exposed to gp120 (500 pmol/L), ddC ($50{\mu}mol/L$), gp120 (500 pmol/L) plus ddC ($50{\mu}mol/L$), gp120 (500 pmol/L) plus IGF-1 (20 nmol/L), ddC ($50{\mu}mol/L$) plus IGF-1 (20 nmol/L), gp120 (500 pmol/L) plus ddC ($50{\mu}mol/L$) plus IGF-1 (20 nmol/L), respectively, for 72 hours. The results showed that gp120 and/or ddC caused neurotoxicity of primary cultured DRG neurons. Interestingly, the severity of neurotoxicity induced by gp120 and ddC was different in different subpopulation of DRG neurons. gp120 mainly affected large diameter DRG neurons (> $25{\mu}m$), whereas ddC mainly affected small diameter DRG neurons (${\leq}25{\mu}m$). IGF-1 could reverse the neurotoxicity induced by gp120 and/or ddC on small, but not large, DRG neurons. These data provide new insights in elucidating the pathogenesis of HIV infection- or antiretroviral therapy-related peripheral neuropathy and facilitating the development of novel treatment strategies.

Keywords

Acknowledgement

Supported by : National Natural Science Foundation of China

References

  1. Acharjee, S., Zhu, Y., Maingat, F., Pardo, C., Ballanyi, K., Hollenberg, M. D. and Power, C. (2011) Proteinase-activated receptor-1 mediates dorsal root ganglion neuronal degeneration in HIV/AIDS. Brain 134 (Pt 11), 3209-3221. https://doi.org/10.1093/brain/awr242
  2. Blackbeard, J., Wallace, V. C., O'Dea, K. P., Hasnie, F., Segerdahl, A., Pheby, T., Field, M. J., Takata, M. and Rice, A. S. (2012) The correlation between pain-related behaviour and spinal microgliosis in four distinct models of peripheral neuropathy. Eur. J. Pain 16, 1357-1367. https://doi.org/10.1002/j.1532-2149.2012.00140.x
  3. Bomze, H. M., Bulsara, K. R., Iskandar, B. J., Caroni, P. and Skene, J. H. (2001) Spinal axon regeneration evoked by replacing two growth cone proteins in adult neurons. Nat. Neurosci. 4, 38-43. https://doi.org/10.1038/82881
  4. Chirivella, L., Cano-Jaimez, M., Perez-Sanchez, F., Herraez, L., Carretero, J., Farinas, I., Burks, D. J. and Kirstein, M. (2012) IRS2 signalling is required for the development of a subset of sensory spinal neurons. Eur. J. Neurosci. 35, 341-352. https://doi.org/10.1111/j.1460-9568.2011.07959.x
  5. Craner, M. J., Klein, J. P., Black, J. A. and Waxman, S. G. (2002) Preferential expression of IGF-I in small DRG neurons and down-regulation following injury. Neuroreport 13, 1649-1652. https://doi.org/10.1097/00001756-200209160-00016
  6. Croci, L., Barili, V., Chia, D., Massimino, L., van Vugt, R., Masserdotti, G., Longhi, R., Rotwein, P. and Consalez, G. G. (2011) Local insulin-like growth factor I expression is essential for Purkinje neuron survival at birth. Cell Death Differ. 18, 48-59. https://doi.org/10.1038/cdd.2010.78
  7. Dalakas, M. C., Semino-Mora, C. and Leon-Monzon, M. (2001) Mitochondrial alterations with mitochondrial DNA depletion in the nerves of AIDS patients with peripheral neuropathy induced by 2'3'-dideoxycytidine (ddC). Lab. Invest. 81, 1537-1544. https://doi.org/10.1038/labinvest.3780367
  8. Gabbai, A. A., Castelo, A. and Oliveira, A. S. (2013) HIV peripheral neuropathy. Handb. Clin. Neurol. 115, 515-529. https://doi.org/10.1016/B978-0-444-52902-2.00029-1
  9. Guan, J. (2008) Insulin-like growth factor-1 and its derivatives: potential pharmaceutical application for ischemic brain injury. Recent Pat. CNS Drug Discov. 3, 112-127. https://doi.org/10.2174/157488908784534630
  10. Hoschele D. (2006) Cell culture models for the investigation of NRTIinduced mitochondrial toxicity. Relevance for the prediction of clinical toxicity. Toxicol. In Vitro 20, 535-546. https://doi.org/10.1016/j.tiv.2005.11.007
  11. Huang, W., Calvo, M., Karu, K., Olausen, H. R., Bathgate, G., Okuse, K., Bennett, D. L. and Rice, A. S. (2013) A clinically relevant rodent model of the HIV antiretroviral drug stavudine induced painful peripheral neuropathy. Pain 154, 560-575. https://doi.org/10.1016/j.pain.2012.12.023
  12. Jones, D. M., Tucker, B. A., Rahimtula, M. and Mearow, K. M. (2003) The synergistic effects of NGF and IGF-1 on neurite growth in adult sensory neurons: convergence on the PI 3-kinase signaling pathway. J. Neurochem. 86, 1116-1128. https://doi.org/10.1046/j.1471-4159.2003.01925.x
  13. Kokotis, P., Schmelz, M., Papadimas, G. K., Skopelitis, E. E., Aroni, K., Kordossis, T. and Karandreas, N. (2013) Polyneuropathy induced by HIV disease and antiretroviral therapy. Clin. Neurophysiol. 124, 176-182. https://doi.org/10.1016/j.clinph.2012.05.022
  14. Lee, M. H., Amin, N. D., Venkatesan, A., Wang, T., Tyagi, R., Pant, H. C. and Nath, A. (2013) Impaired neurogenesis and neurite outgrowth in an HIV-gp120 transgenic model is reversed by exercise via BDNF production and Cdk5 regulation. J. Neurovirol. 19, 418-431. https://doi.org/10.1007/s13365-013-0194-6
  15. Li, H., Dong, H., Li, J., Liu, H., Liu, Z. and Li, Z. (2013) Neuroprotective effect of insulin-like growth factor-1: Effects on tyrosine kinase receptor (Trk) expression in dorsal root ganglion neurons with glutamate-induced excitotoxicity in vitro. Brain Res. Bull. 97C, 86-95.
  16. Liu, H., Lu, J., He, Y., Yuan, B., Li, Y. and Li, X. (2014) Insulin-like growth factor-1 prevents dorsal root ganglion neuronal tyrosine kinase receptor expression alterations induced by dideoxycytidine in vitro. Cell. Mol. Neurobiol 34, 183-194. https://doi.org/10.1007/s10571-013-0001-1
  17. Luma, H. N., Tchaleu, B. C., Doualla, M. S., Temfack, E., Sopouassi, V. N., Mapoure, Y. N. and Djientcheu, V. D. (2012) HIV-associated sensory neuropathy in HIV-1 infected patients at the Douala General Hospital in Cameroon: a cross-sectional study. AIDS Res. Ther. 9, 35. https://doi.org/10.1186/1742-6405-9-35
  18. Lunn, J. S., Pacut, C., Backus, C., Hong, Y., Johe, K., Hefferan, M., Marsala, M. and Feldman, E. L. (2010) The pleotrophic effects of insulin-like growth factor-I on human spinal cord neural progenitor cells. Stem Cells Dev. 19, 1983-1993. https://doi.org/10.1089/scd.2010.0003
  19. Miura, M., Sasaki, M., Mizukoshi, K., Shibasaki, M., Izumi, Y., Shimosato, G., and Amaya, F. (2011) Peripheral sensitization caused by insulin-like growth factor 1 contributes to pain hypersensitivity after tissue injury. Pain 152, 888-895. https://doi.org/10.1016/j.pain.2011.01.004
  20. Myllymaki, M., Panoutsopoulou, I. G. and Sarkka, A. (2012) Analysis of spatial structure of epidermal nerve entry point patterns based on replicated data. J. Microsc. 247, 228-239. https://doi.org/10.1111/j.1365-2818.2012.03636.x
  21. Ng, K., Kumar, K., Brew, B. and Burke, D. (2011) Axonal excitability in viral polyneuropathy and nucleoside neuropathy in HIV patients. J. Neurol. Neurosurg. Psychiatry 82, 978-980. https://doi.org/10.1136/jnnp.2009.203091
  22. Rather, Z. A., Chowta, M. N., Raju, G. J., Mubeen, F. (2013) Evaluation of the adverse reactions of antiretroviral drug regimens in a tertiary care hospital. Indian J. Pharmacol. 45, 145-148. https://doi.org/10.4103/0253-7613.108294
  23. Robinson, B., Li, Z. and Nath, A. (2007) Nucleoside reverse transcriptase inhibitors and human immunodeficiency virus proteins cause axonal injury in human dorsal root ganglia cultures. J. Neurovirol. 13, 160-167. https://doi.org/10.1080/13550280701200102
  24. Schutz, S. G. and Robinson-Papp, J. (2013) HIV-related neuropathy: current perspectives. HIV AIDS 5, 243-251.
  25. Seki, T., Abdel Nazeer, A., Sekimoto, K., Guao, Y., Al-jahdari, W. and Saito, S. (2010) Fibroblast growth factor and insulin-like growth factor rescue growth cones of sensory neurites from collapse after tetracaine-induced injury. Anesth. Analg. 110, 1468-1472. https://doi.org/10.1213/ANE.0b013e3181d31ea6
  26. Shikuma, C., Gerschenson, M., Ananworanich, J., Valcour, V., Teeratakulpisarn, N., Jadwattanakul, T., Degruttola, V., Liang CY, McArthur, J., Ebenezer, G., Chomchey, N., Praihirunkit, P., Hongchookiath, P., Mathajittiphun, P., Nakamoto, B., Hauer, P., Phanuphak, P. and Phanuphak, N. Search 003 protocol team. (2012) Determinants of epidermal nerve fibre density in antiretroviral-naive HIVinfected individuals. HIV Med. 13, 602-608. https://doi.org/10.1111/j.1468-1293.2012.01024.x
  27. Smith, H. S. (2011) Treatment considerations in painful HIV-related neuropathy. Pain Physician 14, E505-524.
  28. Suvada, J. (2013) Neuropathic and neurocongnitive complications of antiretroviral therapy among HIV-infected patients. Neuro Endocrinol. Lett. 34(Suppl1), 5-11.
  29. Wood, T. L., Loladze, V., Altieri, S., Gangoli, N., Levison, S. W., Brywe, K. G., Mallard, C. and Hagberg, H. (2007) Delayed IGF-1 administration rescues oligodendrocyte progenitors from glutamate-induced cell death and hypoxic-ischemic brain damage. Dev. Neurosci. 29, 302-310. https://doi.org/10.1159/000105471
  30. Zheng, W., Ouyang, H., Zheng, X., Liu, S., Mata, M., Fink, D. J. and Hao, S. (2011) Glial $TNF{\alpha}$ in the spinal cord regulates neuropathic pain induced by HIV gp120 application in rats. Mol. Pain 7, 40. https://doi.org/10.1186/1744-8069-7-40
  31. Zheng, W. H. and Quirion, R. (2006) Insulin-like growth factor-1 (IGF-1) induces the activation/phosphorylation of Akt kinase and cAMP response element-binding protein (CREB) by activating different signaling pathways in PC12 cells. BMC Neurosci. 7, 51. https://doi.org/10.1186/1471-2202-7-51

Cited by

  1. Proanthocyanidin B2 attenuates high-glucose-induced neurotoxicity of dorsal root ganglion neurons through the PI3K/Akt signaling pathway vol.13, pp.9, 2018, https://doi.org/10.4103/1673-5374.237174
  2. The delicate balance between neurotoxicity and neuroprotection in the context of HIV‐1 infection vol.69, pp.2, 2014, https://doi.org/10.1002/glia.23904