Skip to main content
SpringerLink
Log in

Reduction of Hippocampal Collapsin Response Mediated Protein-2 in Patients with Mesial Temporal Lobe Epilepsy

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Although the syndrome of mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis has been elaborated in recent years, pathogenesis and pathomechanisms are still elusive. Performing protein hunting in hippocampus of patients with MTLE we detected derangement of collapsin response mediated protein-2 (CRMP-2). Hippocampal tissue from controls and MTLEs was taken and two-dimensional gel electrophoresis with subsequent MALDI-MS-characterisation was applied. The proteomic approach identified 13 spots unambiguously assigned to CRMP-2. Three spots at molecular weight 55 kDa showed a significant decrease in MTLE and other 3 spots at 65 kDa showed deranged in MTLE. Immunoblotting revealed two bands at 65 and 55 kDa in the control group whereas the 55 kDa band was extremely low expressed in MTLE. CRMP-2 is required to induce axonal outgrowth and maintaining neuronal polarity in hippocampal neurons and the significant decrease of this protein may represent or underlie impaired neuronal plasticity, neurodegeneration, wiring of the brain in MTLE and may explain abnormal migration. Therefore, the decrease of CRMP-2 may well contribute to the understanding of the still unclear pathomechanisms involved in MTLE.

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

Similar content being viewed by others

References

  • N. O. Dalby I. Mody (2001) ArticleTitleThe process of epileptogenesis: A pathophysiological approach Curr. Opin. Neurol. 14 187–192

    Google Scholar 

  • S. Pirker T. Czech C. Baumgartner H. Maier K. Novak S. Furtinger R. Fischer-Colbrie G. Sperk (2001) ArticleTitleChromogranins as markers of altered hippocampal circuitry in temporal lobe epilepsy Ann. Neurol. 50 216–226

    Google Scholar 

  • N. Hamajima K. Matsuda S. Sakata N. Tamaki M. Sasaki M. Nonaka (1996) ArticleTitleA novel gene family defined by human dihydropyrimidinase and three related proteins with differential tissue distribution Gene. 180 157–163

    Google Scholar 

  • J. E. Minturn H. J. Fryer D. H. Geschwind S. Hockfield (1995) ArticleTitleTOAD-64, a gene expressed early in neuronal differentiation in the rat, is related to unc-33, a C elegans gene involved in axon outgrowth. J. Neurosci. 15 6757–6766

    Google Scholar 

  • Y. Goshima F. Nakamura P. Strittmatter S. M. Strittmatter (1995) ArticleTitleCollapsin-induced growth cone collapse mediated by an intracellular protein related to UNC-33 Nature. 376 509–514

    Google Scholar 

  • T. Byk T. Dobransky C. Cifuentes-Diaz A. Sobel (1996) ArticleTitleIdentification and molecular characterization of Unc-33-like phosphoprotein (Ulip), a putative mammalian homolog of the axonal guidance-associated unc-33 gene product J. Neurosci. 16 688–701

    Google Scholar 

  • L. H. Wang S. M. Strittmatter (1996) ArticleTitleA family of rat CRMP genes is differentially expressed in the nervous system J. Neurosci. 16 6197–6207

    Google Scholar 

  • H. Inagaki Y. Kato N. Hamajima M. Nonaka M. Sasaki T. Eimoto (2000) ArticleTitleDifferential expression of dihydropyrimidinase-related protein genes in developing and adult enteric nervous system Histochem. Cell. Biol. 113 37–41

    Google Scholar 

  • Y. Gu N. Hamajima Y. Ihara (2000) ArticleTitleNeurofibrillary tangle-associated collapsin response mediator protein-2 (CRMP-2) is highly phosphorylated on Thr-509, Ser-518, and Ser-522 Biochemistry. 39 4267–4275

    Google Scholar 

  • D. Ricard B. Stankoff D. Bagnard M. Aguera V. Rogemond J. C. Antoine N. Spassky B. Zalc C. Lubetzki M. F. Belin J. Honnorat (2000) ArticleTitleDifferential expression of collapsin response mediator proteins (CRMP/ULIP) in subsets of oligodendrocytes in the postnatal rodent brain Mol. Cell. Neurosci. 16 324–327

    Google Scholar 

  • Y. Fukata T. J. Itoh T. Kimura C. Menager T. Nishimura T. Shiromizu H. Watanabe N. Inagaki A. Iwamatsu H. Hotani K. Kaibuchi (2002) ArticleTitleCRMP-2 binds to tubulin heterodimers to promote microtubule assembly Nat. Cell. Biol. 4 583–591

    Google Scholar 

  • G. D. Jackson S. F. Berkovic J. S. Duncan A. Connelly (1993) ArticleTitleOptimising the diagnosis of hippocampal sclerosis using magnetic resonance imaging Am. J. Neuroradiol. 14 753–762

    Google Scholar 

  • T. L. Babb W. J. Brown (1987) Pathological findings in epilepsy J. Jr. Engel (Eds) Surgical treatment of epilepsies Raven Press New York 511–540

    Google Scholar 

  • M. M. Bradford (1976) ArticleTitleA rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding Anal. Biochem. 76 248–254

    Google Scholar 

  • M. Fountoulakis R. Hardmaier E. Schuller G. Lubec (2000) ArticleTitleDifferences in protein level between neonatal and adult brain Electrophoresis. 21 673–678

    Google Scholar 

  • D. Suckau A. Resemann M. Schuerenberg P. Hufnagel J. Franzen A. Holle (2003) ArticleTitleA novel MALDI LIFT-TOF/TOF mass spectrometer for proteomics Anal. Bioanal. Chem. 376 952–965

    Google Scholar 

  • G. Lubec M. Nonaka K. Krapfenbauer M. Gratzer N. Cairns M. Fountoulakis (1999) ArticleTitleExpression of the dihydropyrimidinase related protein 2 (DRP-2) in Down syndrome and Alzheimer’s disease brain is downregulated at the mRNA and dysregulated at the protein level J. Neural. Transm. Suppl. 57 161–177

    Google Scholar 

  • N. Arimura N. Inagaki K. Chihara C. Menager N. Nakamura M. Amano A. Iwamatsu Y. Goshima K. Kaibuchi (2000) ArticleTitlePhosphorylation of collapsin response mediator protein-2 by Rho-kinase.Evidence for two separate signaling pathways for growth cone collapse. J. Biol. Chem. 275 23973–23980

    Google Scholar 

  • C. Gaetano T. Matsuo C. J. Thiele (1997) ArticleTitleIdentification and characterization of a retinoic acid-regulated human homologue of the unc-33-like phosphoprotein gene (hUlip) from neuroblastoma cells J. Biol. Chem. 272 12195–12201

    Google Scholar 

  • C. Hall M. Brown T. Jacobs G. Ferrari N. Cann M. Teo C. Monfries L. Lim (2001) ArticleTitleCollapsin response mediator protein switches RhoA and Rac1 morphology in N1E-115 neuroblastoma cells and is regulated by Rho kinase J. Biol. Chem. 276 43482–43486

    Google Scholar 

  • W. Li R. K. Herman J. E. Shaw (1992) ArticleTitleAnalysis of the Caenorhabditis elegans axonal guidance and outgrowth gene unc-33 Genetics. 132 675–689

    Google Scholar 

  • T. L. Babb W. R. Kupfer J. K. Pretorius P. H. Crandall M. F. Levesque (1991) ArticleTitleSynaptic reorganization by mossy fibers in human epileptic fascia dentate Neuroscience. 42 351–363

    Google Scholar 

  • I. Blümcke H. Beck A. A. Lie O. D. Wiestler (1999) ArticleTitleMolecular neuropathology of human mesial temporal lobe epilepsy Epilepsy Res. 36 205–223

    Google Scholar 

  • S. Furtinger S. Pirker T. Czech C. Baumgartner G. Ransmayr G. Sperk (2001) ArticleTitlePlasticity of Y1 and Y2 receptors and neuropeptide Y fibers in patients with temporal lobe epilepsy J. Neurosci. 21 5804–5812

    Google Scholar 

  • J. A. Gorter F. H.> da Silva (2002) ArticleTitleAbnormal plastic changes in a rat model for mesial temporal lobe epilepsy: A short review Prog. Brain Res. 138 61–72

    Google Scholar 

  • M. Isokawa M. F. Levesque T. L. Babb J. Engel SuffixJr. (1993) ArticleTitleSingle mossy fiber axonal systems of human dentate granule cells studied in hippocampal slices from patients with temporal lobe epilepsy J. Neurosci. 13 1511–1522

    Google Scholar 

  • N. C. Lanerolle Particlede J. H. Kim R. J. Robbins D. D. Spencer (1989) ArticleTitleHippocampal interneuron loss and plasticity in human temporal lobe epilepsy Brain Res. 495 387–395

    Google Scholar 

  • P. S. Buckmaster G. F. Zhang R. Yamawaki (2002) ArticleTitleAxon sprouting in a model of temporal lobe epilepsy creates a predominantly excitatory feedback circuit J. Neurosci. 22 6650–6658

    Google Scholar 

  • H. Beck I. V. Goussakov A. Lie C. Helmstaedter C. E. Elger (2000) ArticleTitleSynaptic plasticity in the human dentate gyrus J. Neurosci. 15 7080–7086

    Google Scholar 

  • N. Inagaki K. Chihara N. Arimura C. Menager Y. Kawano N. Matsuo T. Nishimura M. Amano K. Kaibuchi (2001) ArticleTitleCRMP-2 induces axons in cultured hippocampal neurons Nat. Neurosci. 4 781–782

    Google Scholar 

  • R. Weitzdoerfer M. Fountoulakis G. Lubec (2001) ArticleTitleAberrant expression of dihydropyrimidinase related proteins-2,-3 and -4 in fetal Down syndrome brain J. Neural. Transm. Suppl. 61 95–107

    Google Scholar 

  • A. Castegna M. Aksenov V. Thongboonkerd J. B. Klein W. M. Pierce R. Booze W. R. Markesbery D. A. Butterfield (2002) ArticleTitleProteomic identification of oxidatively modified proteins in Alzheimer’s disease brain.Part II: Dihydropyrimidinase-related protein 2 alpha-enolase and heat shock cognate 71. J. Neurochem. 82 1524–1532

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurosurgery, University of Vienna, Waehringer Guertel 18, Vienna, Austria, A-1090

    Thomas Czech

  2. Department of Pediatrics, University of Vienna, Waehringer Guertel 18, Vienna, Austria, A-1090

    Jae-Won Yang & Gert Lubec

  3. Mass Spectrometry Unit, University of Vienna, Dr. Bohr-Gasse 9, Vienna, Austria, A-1030

    Edina Csaszar

  4. Institut für Physiologische Chemie, Rheinische Friedrich-Wilhelms-Universität Bonn, Nussallee 11, Bonn, Germany, D-53114

    Joachim Kappler

  5. Section of Clinical Epilepsy Research Department of Neurology, University of Vienna, Waehringer Guertel 18, Vienna, Austria, A-1090

    Christoph Baumgartner

Authors
  1. Thomas Czech
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jae-Won Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Edina Csaszar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joachim Kappler
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christoph Baumgartner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gert Lubec
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gert Lubec.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Czech, T., Yang, JW., Csaszar, E. et al. Reduction of Hippocampal Collapsin Response Mediated Protein-2 in Patients with Mesial Temporal Lobe Epilepsy. Neurochem Res 29, 2189–2196 (2004). https://doi.org/10.1007/s11064-004-7025-3

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-004-7025-3

Keywords

Search

Navigation