Skip to main content
SpringerLink
Log in

Down-Regulation of CRMP-1 in Patients with Epilepsy and a Rat Model

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

The Collapsin Response Mediator Protein-1 (CRMP-1) is a brain specific protein identified as a signaling molecule of Semaphorin-3A and act as axon repellent guidance factor in nervous system. Recent studies indicated that axon guidance molecules may play a role in synaptic reorganization in the adult brain and thereby promote epileptogenesis. This study aimed to investigate expression pattern of CRMP-1 in epileptogenesis. Using double immunofluorescence labeling, immunohistochemistry and western blot analysis, we looked into the CRMP-1 expression in temporal neocortex from patients with temporal lobe epilepsy (TLE) and histological normal temporal neocortex from the controls. We also studied the expression pattern of CRMP-1 in hippocampus and adjacent cortex of a TLE rat model on 6, 24, 72 h, 1, 2 weeks, 1 month, and 2 months post-seizure, and from control rats. CRMP-1 was mainly expressed in the neuronal cytoplasm in the temporal lobe of intractable TLE patients, which was co-expressed with -2. CRMP-1 expression was downregulated in temporal neocortical of TLE patients. In addition, in pilocarpine-induced animal model of epilepsy, CRMP-1 dynamically decreased in a range of 2 months. Thus, our results indicate that CRMP-1 may be involved in the development of TLE.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Babb T, Kupfer W, Pretorius J, Crandall P, Levesque M (1991) Synaptic reorganization by mossy fibers in human epileptic fascia dentata. Neuroscience 42:351–363

    Article  PubMed  CAS  Google Scholar 

  2. Barnes G, Puranam RS, Luo Y, McNamara JO (2003) Temporal specific patterns of semaphorin gene expression in rat brain after kainic acid©\induced status epilepticus. Hippocampus 13:1–20

    Article  PubMed  CAS  Google Scholar 

  3. Beleza P (2009) Refractory epilepsy: a clinically oriented review. Eur Neurol 62:65–71

    Article  PubMed  Google Scholar 

  4. Bialer M, White HS (2010) Key factors in the discovery and development of new antiepileptic drugs. Nat Rev Drug Discov 9:68–82

    Article  PubMed  CAS  Google Scholar 

  5. Borges K, Gearing M, McDermott DL, Smith AB, Almonte AG, Wainer BH, Dingledine R (2003) Neuronal and glial pathological changes during epileptogenesis in the mouse pilocarpine model. Exp Neurol 182:21–34

    Article  PubMed  CAS  Google Scholar 

  6. Bragin A, Engel J Jr, Wilson CL, Vizentin E, Mathern GW (1999) Electrophysiologic analysis of a chronic seizure model after unilateral hippocampal KA injection. Epilepsia 40:1210–1221

    Article  PubMed  CAS  Google Scholar 

  7. Bretin S, Reibel S, Charrier E, Maus©\Moatti M, Auvergnon N, Thevenoux A, Glowinski J, Rogemond V, Pr¨¦mont J, Honnorat J (2005) Differential expression of CRMP1, CRMP2A, CRMP2B, and CRMP5 in axons or dendrites of distinct neurons in the mouse brain. J Comp Neurol 486:1–17

    Article  PubMed  CAS  Google Scholar 

  8. Cheng HJ, Bagri A, Yaron A, Stein E, Pleasure SJ, Tessier-Lavigne M (2001) Plexin-A3 mediates semaphorin signaling and regulates the development of hippocampal axonal projections. Neuron 32:249–263

    Article  PubMed  CAS  Google Scholar 

  9. Czech T, Yang JW, Csaszar E, Kappler J, Baumgartner C, Lubec G (2004) Reduction of hippocampal collapsin response mediated protein-2 in patients with mesial temporal lobe epilepsy. Neurochem Res 29:2189–2196

    Article  PubMed  CAS  Google Scholar 

  10. Dickson BJ (2002) Molecular mechanisms of axon guidance. Science 298:1959

    Article  PubMed  CAS  Google Scholar 

  11. Fang M, Liu GW, Pan YM, Shen L, Li CS, Xi ZQ, Xiao F, Wang L, Chen D, Wang XF (2010) Abnormal expression and spatiotemporal change of Slit2 in neurons and astrocytes in temporal lobe epileptic foci: a study of epileptic patients and experimental animals. Brain Res 1324:14–23

    Article  PubMed  CAS  Google Scholar 

  12. Fang M, Xi ZQ, Wu Y, Wang XF (2011) A new hypothesis of drug refractory epilepsy: neural network hypothesis. Med Hypotheses

  13. French JA (2007) Refractory epilepsy: clinical overview. Epilepsia 48:3–7

    Article  PubMed  Google Scholar 

  14. Gassmann M, Grenacher B, Rohde B, Vogel J (2009) Quantifying western blots: pitfalls of densitometry. Electrophoresis 30:1845–1855

    Article  PubMed  CAS  Google Scholar 

  15. Goshima Y, Nakamura F, Strittmatter P, Strittmatter SM (1995) Collapsin-induced growth cone collapse mediated by an intracellular protein related to UNC-33. Nature 376:509–514

    Article  PubMed  CAS  Google Scholar 

  16. Holtmaat AJGD, Gorter JA, Wit JD, Tolner EA, Spijker S, Giger RJ, Lopes da Silva FH, Verhaagen J (2003) Transient downregulation of sema3a mrna in a rat model for temporal lobe epilepsy: a novel molecular event potentially contributing to mossy fiber sprouting. Exp Neurol 182:142–150

    Article  PubMed  CAS  Google Scholar 

  17. Kurnellas M, Li H, Jain M, Giraud S, Nicot A, Ratnayake A, Heary R, Elkabes S (2010) Reduced expression of plasma membrane calcium ATPase 2 and collapsin response mediator protein 1 promotes death of spinal cord neurons. Cell Death Differ 17:1501–1510

    Article  PubMed  CAS  Google Scholar 

  18. Kwan P, Brodie MJ (2000) Early identification of refractory epilepsy. N Engl J Med 342:314–319

    Article  PubMed  CAS  Google Scholar 

  19. Luo J, Xu Y, Zhu Q, Zhao F, Zhang Y, Peng X, Wang W, Wang X (2011) Expression pattern of Mical-1 in the temporal neocortex of patients with intractable temporal epilepsy and pilocarpine-induced rat model. Synapse 65:1213–1221

    Article  PubMed  CAS  Google Scholar 

  20. Majores M, Schoch S, Lie A, Becker AJ (2007) Molecular neuropathology of temporal lobe epilepsy: complementary approaches in animal models and human disease tissue. Epilepsia 48:4–12

    Article  PubMed  CAS  Google Scholar 

  21. Mello LEAM, Cavalheiro EA, Tan AM, Kupfer WR, Pretorius JK, Babb TL, Finch DM (1993) Circuit mechanisms of seizures in the pilocarpine model of chronic epilepsy: cell loss and mossy fiber sprouting. Epilepsia 34:985–995

    Article  PubMed  CAS  Google Scholar 

  22. Pan Y, Liu G, Fang M, Shen L, Wang L, Han Y, Shen D, Wang X (2010) Abnormal expression of netrin-G2 in temporal lobe epilepsy neurons in humans and a rat model. Exp Neurol 224:340–346

    Article  PubMed  CAS  Google Scholar 

  23. Pasterkamp RJ, Giger RJ (2009) Semaphorin function in neural plasticity and disease. Curr Opin Neurobiol 19:263–274

    Article  PubMed  CAS  Google Scholar 

  24. Peng X, Zhang X, Wang L, Zhu Q, Luo J, Wang W, Wang X (2011) Gelsolin in cerebrospinal fluid as a potential biomarker of epilepsy. Neurochem Res 36:2250–2258

    Article  PubMed  CAS  Google Scholar 

  25. Pitk nen A, Lukasiuk K (2009) Molecular and cellular basis of epileptogenesis in symptomatic epilepsy. Epilepsy Behav 14:16–25

    Article  Google Scholar 

  26. Pitkanen A, Lukasiuk K (2011) Mechanisms of epileptogenesis and potential treatment targets. Lancet Neurol 10:173–186

    Article  PubMed  Google Scholar 

  27. Racine RJ (1972) Modification of seizure activity by electrical stimulation: II motor seizure. Electroencephalogr Clin Neurophysiol 32:281–294

    Article  PubMed  CAS  Google Scholar 

  28. Rakhade SN, Jensen FE (2009) Epileptogenesis in the immature brain: emerging mechanisms. Nat Rev Neurol 5:380–391

    Article  PubMed  CAS  Google Scholar 

  29. Schmidt EF, Strittmatter SM (2007) The CRMP family of proteins and their role in Sema3A signaling. Semaphorins Receptor Intracellular Signal Mech 600:1–11

    Article  Google Scholar 

  30. Shibley H, Smith BN (2002) Pilocarpine-induced status epilepticus results in mossy fiber sprouting and spontaneous seizures in C57BL/6 and CD-1 mice. Epilepsy Res 49:109–120

    Article  PubMed  CAS  Google Scholar 

  31. Sisodiya S, Lin WR, Harding B, Squier M, Thom M (2002) Drug resistance in epilepsy: expression of drug resistance proteins in common causes of refractory epilepsy. Brain 125:22

    Article  PubMed  CAS  Google Scholar 

  32. Su KY, Chien WL, Fu WM, Yu I (2007) Mice deficient in collapsin response mediator protein-1 exhibit impaired long-term potentiation and impaired spatial learning and memory. J Neurosci 27:2513

    Article  PubMed  CAS  Google Scholar 

  33. Sutula T, He XX, Cavazos J, Scott G (1988) Synaptic reorganization in the hippocampus induced by abnormal functional activity. Science 239:1147

    Article  PubMed  CAS  Google Scholar 

  34. Teng J, Takei Y, Harada A, Nakata T, Chen J, Hirokawa N (2001) Synergistic effects of MAP2 and MAP1B knockout in neuronal migration, dendritic outgrowth, and microtubule organization. J Cell Biol 155:65

    Article  PubMed  CAS  Google Scholar 

  35. Torres R, Polymeropoulos MH (1998) Genomic organization and localization of the human CRMP-1 gene. DNA Res 5:393

    Article  PubMed  CAS  Google Scholar 

  36. Vezzani A, French J, Bartfai T, Baram TZ (2010) The role of inflammation in epilepsy. Nat Rev Neurol 7:31–40

    Article  PubMed  Google Scholar 

  37. Wang LH, Strittmatter SM (1996) A family of rat CRMP genes is differentially expressed in the nervous system. J Neurosci 16:6197

    PubMed  CAS  Google Scholar 

  38. Xi ZQ, Xiao F, Yuan J, Wang XF, Wang L, Quan FY, Liu GW (2009) Gene expression analysis on anterior temporal neocortex of patients with intractable epilepsy. Synapse 63:1017–1028

    Article  PubMed  CAS  Google Scholar 

  39. Yamashita N, Morita A, Uchida Y, Nakamura F, Usui H, Ohshima T, Taniguchi M, Honnorat J, Thomasset N, Takei K (2007) Regulation of spine development by semaphorin3A through cyclin-dependent kinase 5 phosphorylation of collapsin response mediator protein 1. J Neurosci 27:12546

    Article  PubMed  CAS  Google Scholar 

  40. Yin H, Wang L, Xiao F, Huang Z, Huang Y, Zhou C, Han Y, Tao S, Yang H, Wang X (2011) Upregulation of liprin-α1 protein in the temporal neocortex of intractable epileptic patients and experimental rats. Synapse 65:742–750

    Article  PubMed  CAS  Google Scholar 

  41. Zeng K, Wang X, Wang Y, Yan Y (2009) Enhanced synaptic vesicle traffic in hippocampus of phenytoin-resistant kindled rats. Neurochem Res 34:899–904

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by National Natural Science Foundation of China (NO81071039), and the Natural Science Foundation of Chongqing (CSTC, 2008BB5076).The authors sincerely thank the subjects and their families for their participation in this study.

Author information

Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China

    Jing Luo, Kebin Zeng, Chengqu Zhang, Min Fang, Xiaogang Zhang, Qiong Zhu, Liang Wang, Xuefeng Wang & Guojun Chen

  2. Department of Neurology, The Affiliated Hospital of Guiyang Medical College, Guiyang, 550004, Guizhou, China

    Wei Wang

Authors
  1. Jing Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kebin Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chengqu Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Min Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiaogang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qiong Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Liang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Wei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xuefeng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Guojun Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Xuefeng Wang or Guojun Chen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Luo, J., Zeng, K., Zhang, C. et al. Down-Regulation of CRMP-1 in Patients with Epilepsy and a Rat Model. Neurochem Res 37, 1381–1391 (2012). https://doi.org/10.1007/s11064-012-0712-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-012-0712-6

Keywords

Search

Navigation