Abstract
Temporal lobe epilepsy (TLE), the most common type of epilepsy in humans, is frequently associated with hippocampal sclerosis, cognitive deficit, and pharmacoresistant seizures. A major difficulty in designing new treatments to block seizures or epileptogenesis is the sequence of events involved in the development of the epileptic circuitry after an initial insult in the brain. The neuroproteomics emerges as a powerful tool for researchers interested in pursuing biomarkers for neurodegenerative diseases, including TLE. In this chapter, we present data obtained from studies employing proteomics technology to determine differential expression of proteins in brain tissue or cerebrospinal fluid of patients with TLE and in experimental models of epilepsy. Based on the findings it is possible to identify similarities of protein changes related to TLE in humans and models. Data obtained with proteomics are very useful to understand the pathophysiology of TLE and in the future may assist in finding target proteins for new therapies.
Keywords
- Temporal lobe epilepsy
- Proteomics
- Neuroproteomics
- Pharmacoresistant seizures
- Hippocampus
- Pilocarpine
- Status epilepticus
This is a preview of subscription content, access via your institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Adibhatla RM, Hatcher JF. Altered lipid metabolism in brain injury and disorders. Subcell Biochem. 2008;49:241–68. doi:10.1007/978-1-4020-8831-5_9.
Aker RG, Yananli HP, Gurbanova AA, Özkaynakça AE, Ates N, Luijtelaar G, et al. Amygdale kindling in the WAG/Rij rat model of absence epilepsy. Epilepsia. 2006;47:33–40. doi:10.1111/j.1528-1167.2006.00367.x.
Akman O, Karson A, Aker EG, Ates N, Onat FY. Hippocampal kindling in rats with absence epilepsy resembles amygdaloid kindling. Epilepsy Res. 2008;81:211–9. doi:10.1016/j.eplepsyres.2008.06.004.
Akman O, Karson A, Aker EG, Ates N, Onat FY. Perirhinal cortical kindling in rats with genetic absence epilepsy. Neurosci Lett. 2010;479:74–8. doi:10.1016/j.neulet.2010.05.034.
Alzate O. Neuroproteomics. In: Alzate O, editor. Neuroproteomics. Boca Raton, FL: CRC Press; 2010.
Babb TL, Kupfer WR, Pretorius JK, Crandall PH, Levesque MF. Synaptic reorganization by mossy fibers in human epileptic fascia dentata. Neuroscience. 1991;42:351–63. doi:10.1016/0306-4522(91)90380-7.
Ben-Ari Y. Limbic seizures and brain damage produced by kainic acid: mechanisms and relevance to human temporal lobe epilepsy. Neuroscience. 1985;14:375–403.
Buckmaster PS. Laboratory animal models of temporal lobe epilepsy. Comp Med. 2004;54:473–85.
Castegna A, Aksenov M, Thongboonkerd V, Pierce WM, Booze R, Markesbery WR, et al. Proteomic identification of oxidatively modified profiles proteins in Alzheimer’s disease brain. Part II: dihydropyrimidinase-related protein 2, alpha-enolase and heat shock cognate 71. J Neurochem. 2002;82:1524–32. doi:10.1046/j.1471-4159.2002.01103.x.
Cavalheiro EA. The pilocarpine model of epilepsy. Italian J Neurol Sci. 1995;16:33–7. doi:10.1007/BF02229072.
Cavalheiro EA, Leite JP, Bortolotto ZA, Turski WA, Ikonomidou C, Turski L. Long-termeffects of pilocarpine in rats: structural damage of the brain triggers kindling and spontaneously recurrent seizures. Epilepsia. 1991;32:778–82. doi:10.1111/j.1528-1157.1991.tb05533.x.
Conboy L, Varea E, Castro JE, Sakaouhi-Ouertatani H, Calandra T, Lashuel HA, et al. Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hipocampal cell proliferation and in anxiety, depression, and memory-related behaviors. Mol Psychiatry. 2011;16:533–47. doi:10.1038/mp. 2010.15.
Czech T, Yang JW, Csaszar E, Kappler J, Baumgartner C, Lubec G. Reduction of hippocampal collapsin response mediated protein-2 in patients with mesial temporal lobe epilepsy. Neurochem Res. 2004;29:2189–96. doi:0364-3190/04/1200-2189/0.
Danis O, Demir S, Günel A, Aker RG, Gülçebi M, Onat F, et al. Changes in intracellular protein expression in cortex, thalamus and hippocampus in a genetic rat model of absence epilepsy. Brain Res Bull. 2011;84:381–8. doi:10.1016/j.brainresbull.2011.02.002.
Danober L, Deransart C, Depaulis A, Vergnes M, Marescaux C. Pathophysiological mechanisms of genetic absence epilepsy in the rat. Prog Neurobiol. 1998;55:27–57. PII: S0301-0082(97)00091-9.
Di Ciero L, Bellato CM. Proteoma: avanços recentes em técnicas de eletroforese bidimensional e espectrometria de massa. Biotecnol Clin Desenvolv. 2003;29:158–64. http://www.biotecnologia.com.br/revista/bio29/proteoma.pdf. Acessed 24 Aug 2012.
Engel J. Clinical aspects of epilepsy. Epilepsy Res. 1991;10:9–17.
Engel Jr J. Introduction to temporal lobe epilepsy. Epilepsy Res. 1996;26:141–50. doi:10.1016/S0920-1211(96)00043-5.
Engel Jr J. A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology. Epilepsia. 2001;42:796–803. doi:10.1046/j.1528-1157.2001.10401.x.
Eun JP, Choi HY, Kwak YG. Proteomic analysis of human cerebral cortex in epileptic patients. Exp Mol Med. 2004;36:185–91.
Fountoulakis M. Proteomics: current technologies and applications in neurological disorders and toxicology. Amino Acids. 2001;21:363–81. doi:10.1007/s007260170002.
Fountoulakis M, Takács B. Enrichment and proteomic analysis of low-abundance bacterial proteins. Methods Enzymol. 2002;358:288–306. doi:10.1016/S0076-6879(02)58096-4.
French JA, Williamson PD, Thadani VM, Darcey TM, Mattson RH, Spencer SS, et al. Characteristics of medial temporal lobe epilepsy: I. Results of history and physical examination. Ann Neurol. 1993;34:774–80. doi:10.1002/ana.410340604.
French JA, Kanner AM, Bautista J, Abou-Khalil B, Browne T, Harden CL, et al. Efficacy and tolerability of the new antiepileptic drugs I: treatment of new onset epilepsy. Neurology. 2004;62:1252–60.
Greenberg DA, Cayanis E, Strug L, Sudhir M, Durner M, Pal DK, et al. Malic Enzyme 2 underline susceptibility to adolescent-onset idiopatic generalized epilepsy. Am J Hum Genet. 2005;76:139–46. doi:10.1086/426735.
House CR, Miyashiro JE, Swartz BE, Walsh GO, Rich JR, Delgado-Escueta AV. Altered patterns of dynorphin immunoreactivity suggest mossy fiber reorganization in human hippocampal epilepsy. J Neurosci. 1990;10:267–82. doi:0270-6474/90/010267-16$02.00/0.
Huang ZL, Zhou Y, Xiao B, Wu J, Wu XM, Yang P, et al. Proteomic screening of postsynaptic density proteins related with temporal lobe epilepsy. Zhonghua Yi Xue Za Zhi. 2008;88:3205–9.
Kasper BS, Stefan H, Buchfelder M, Paulus W. Temporal lobe microdysgenesis in epilepsy versus control brains. J Neuropathol Exp Neurol. 1999;58:22–8. doi:00005072-199901000-00003.
Kim H, Eliuk S, Deshane J, Meleth S, Sanderson T, Pinner A, et al. 2D gel proteomics: an approach to study age-related differences in protein abundance or isoform complexity in biological samples. Methods Mol Biol. 2007;371:349–91. doi:10.1007/978-1-59745-361-5_24.
Li LM, Sander JW. National demonstration project on epilepsy in Brazil. Arq Neuropsiquiatr. 2003;61:153–6. doi:10.1590/S0004-282X2003000100033.
Li KW, Smit AB. Subcellular proteomics in neuroscience. Front Biosci. 2008;13:4416–25. doi:doi.org/10.2741/3014.
Li Z, Burrone J, Tyler WJ, Hartman KN, Albeanu DF, Murthy VN. Synaptic vesicle recycling studied in transgenic mice expressing synaptopHluorin. Proc Natl Acad Sci USA. 2005;102:6131–6. doi:10.1073/pnas.0501145102.
Liu X, Wen F, Yang J, Chen L, Wei YQ. A review of current applications of mass spectrometry for neuroproteomics in epilepsy. Mass Spectrom Rev. 2010;29:197–246. doi:10.1002/mas.20243.
Lo WY, Tsai FJ, Liu CH, Tang NY, Su SY, Lin SZ, et al. Uncaria rhynchophylla upregulates the expression of MIF and cyclophilin A in kainic acid-induced epilepsy rats: a proteomic analysis. Am J Chin Med. 2010;38:745–59. doi:10.1142/S0192415X10008214.
Marchi N, Teng Q, Ghosh C, Fan Q, Nguyen MT, Desai NK, et al. Blood-brain barrier damage, but not parenchymal white blood cells, is a hallmark of seizure activity. Brain Res. 2010;1353:176–86. doi:10.1016/j.brainres.2010.06.051.
Martins-de-Souza D, Gattaz WF, Schmitt A, Novello JC, Marangoni S, Turck CW, et al. Proteome analysis of schizophrenia patients Wernicke’s area reveals an energy metabolism dysregulation. BMC Psychiatry. 2009;9:17. doi:10.1186/1471-244X-9-17.
Masino SA, Kawamura M, Wasser CD, Pomeroy LT, Ruskin DN. Adenosine, ketogenic diet and epilepsy: the emerging therapeutic relationship between metabolism and brain activity. Curr Neuropharmacol. 2009;7:257–68. doi:10.2174/157015909789152164.
Mathern GW, Babb TL, Vickrey BG, Melendez M, Pretorius JK. The clinical-pathogenic mechanisms of hippocampal neuron loss and surgical outcomes in temporal lobe epilepsy. Brain J Neurol. 1995;118:105–18. doi:10.1093/brain/118.1.105.
Mayer MP, Bukau B. Hsp70 chaperones: cellular functions and molecular mechanism. Cell Mol Life Sci. 2005;62:670–84. doi:10.1007/s00018-004-4464-6.
Mus-Veteau I. Heterologous expression and purification systems for structural proteomics of mammalian membrane proteins. Comp Funct Genomics. 2002;3:511–7. doi:10.1002/cfg.218.
Neves SR, Ram PT, Iyengar R. G protein pathways. Science. 2002;296:1636–9. doi:10.1126/science.1071550.
Onat FY, Aker RG, Gurbanova AA, Ates N, Luijtelaar G. The effect of generalized absence seizures on the progression of kindling in the rat. Epilepsia. 2007;5:150–6. doi:10.1111/j.1528-1167.2007.01303.x.
Pappin DJ, Hojrup P, Bleasby AJ. Rapid identification of proteins by peptide-mass fingerprinting. Curr Biol. 1993;3:327–32. doi:10.1016/0960-9822(93)90195-T.
Persike DS, Casarini DE, Lima ML, Amorim RP, Yacubian EMT, Centeno R, Canzian M, Fernandes MJS. Differential expression of proteins in the hippocampus of patients with temporal lobe epilepsy. In: 8th Ibro World Congress of Neuroscience. International Brain Research Organization, Florence. 2011. http://www.ibro2011.org.
Persike DS, Lima ML, Amorim RP, Araújo MGL, Sierra LF, Cavalheiro EA, Schenkman S, Fernandes MJS. Proteomics profile of rat hippocampus subjected to the pilocarpine model of epilepsy. In: XXVII Annual FeSBE Meeting. Serviço de Biblioteca e Informação Biomédica do Instituto de Ciências Biomédicas da Universidade de São Paulo, Águas de Lindóia. 2012. http://www.fesbe.org.br/fesbe2012.
Ross BM, Hudson C, Erlich J, Warsh JJ, Kish SJ. Increased phospholipid breakdown in schizophrenia. Evidence for the involvement of a calcium independent phospholipase A2. Arch Gen Psychiatry. 1997;54:487–94. doi:00000756-199705000-00012.
Shang W, Liu WH, Zhao XH, Sun QJ, Bi JZ, Chi ZF. Expressions of glutathione S-transferase alpha, mu, and pi in brains of medically intractable epileptic patients. BMC Neurosci. 2008;9:67. doi:10.1186/1471-2202-9-67.
Sharma R, Yang Y, Sharma A, Awasthi S, Awasthi YC. Antioxidant role of glutathione S-transferases: protection against oxidant toxicity and regulation of stress-mediated apoptosis. Antioxid Redox Signal. 2004;6:289–300. doi:10.1089/152308604322899350.
Silva AV, Cabral FR. Ictogênese, Epileptogênese e Mecanismo de Ação das Drogas na Profilaxia e Tratamento da Epilepsia. J Epilepsy Clin Neurophysiol. 2008;14:39–45.
Talib LL, Yassuda MS, Diniz BSO, Forlenza OV, Gattaz WF. Cognitive training increases platelet PLA2 activity in healthy elderly subjects. Prostaglandins Leukot Essent Fatty Acids. 2008;78:265–9. doi:10.1016/j.plefa.2008.03.002.
Temkin NR. Preventing and treating posttraumatic seizures: the human experience. Epilepsia. 2009;50:10–3. doi:10.1111/j.1528-1167.2008.02005.x.
Ujike H, Sakai A, Tanaka Y, Kodaka T, Okahisa Y, Harano M, et al. Association study of the dihydropyrimidinase-related protein 2 gene and methamphetamine psychosis. Ann N Y Acad Sci. 2006;1074:90–6. doi:10.1196/annals.1369.008.
Van den Bergh G, Arckens L. Recent advances in 2D electrophoresis: an array of possibilities. Expert Rev Proteomics. 2005;2:243–52. doi:10.1586/14789450.2.2.243.
Wang YY, Smith P, Murphy M, Cook M. Global expression profiling in epileptogenesis: does it add to the confusion? Brain Pathol. 2010;20:1–16. doi:10.1111/j.1750-3639.2008.00254.x.
Wechsler A, Teichberg VI. Brain spectrin binding to the NMDA receptor is regulated by phosphorylation, calcium and calmodulin. EMBO J. 1998;17:3931–9. doi:10.1093/emboj/17.14.3931.
Wilkens S, Zhang Z, Zheng Y. A structural model of the vacuolar ATPase from transmission electron microscopy. Micron. 2005;36:109–26. doi:10.1016/j.micron.2004.10.002.
Wilkins MR, Sanchez IC, Gooley AA, Appel RD, Humphery-Smith I, Hochstrasser DF, et al. Progress with proteome projects: why all proteins expressed by a genome should be identified and how to do it. Biotechnol Genet Eng Rev. 1996;13:19–50. doi:0264-8725/94/12/1-38$20.00+$0.00.
Xiao F, Chen D, Lu Y, Xiao Z, Guan LF, Yuan J, et al. Proteomic analysis of cerebrospinal fluid from patients with idiopathic temporal lobe epilepsy. Brain Res. 2009;1255:180–9. doi:10.1016/j.brainres.2008.12.008.
Yang JW, Czech T, Yamada J, Csaszar Z, Baumgartner C, Slavc I, et al. Aberrant cytosolic acyl-CoA thioester hydrolase in hippocampus of patients with mesial temporal lobe epilepsy. Amino Acids. 2004;27:269–75. doi:10.1007/s00726-004-0138-9.
Yang JW, Czech T, Gelpi E, Lubec G. Extravasation of plasma proteins can confound interpretation of proteomic studies of brain: a lesson from apo A-I in mesial temporal lobe epilepsy. Mol Brain Res. 2005;139:348–56. doi:10.1016/j.molbrainres.2005.06.010.
Yang JW, Czech T, Felizardio M, Baumgartner C, Lubec G. Aberrant expression of cytoskeleton proteins in hippocampus from patients with mesial temporal lobe epilepsy. Amino Acids. 2006;30:477–93. doi:10.1007/s00726-005-0281-y.
Zetterberg FL, Ruetschi U, Portelius E, Brinkmalm G, Andreasson U, Blennow K, et al. Clinical proteomics in neurodegenerative disorders. Acta Neurol Scand. 2008;118:1–11. doi:10.1111/j.1600-0404.2007.00985.x.
Acknowledgements
The authors thank Fapesp, CNPq, CAPES, and INNT/MCT for financial support and UNIPETE-UNIFESP.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
da Silva Fernandes, M.J., Amorim, R.P., Carneiro, J.E.M., Araújo, M.G.L., Persike, D.S. (2013). Proteomics-Based Strategy to Identify Biomarkers and Pharmacological Targets in Temporal Lobe Epilepsy. In: Rocha, L., Cavalheiro, E. (eds) Pharmacoresistance in Epilepsy. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6464-8_8
Download citation
DOI: https://doi.org/10.1007/978-1-4614-6464-8_8
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-6463-1
Online ISBN: 978-1-4614-6464-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)