Skip to main content

Advertisement

SpringerLink
Log in

The Effects of Topiramate on Caspase-3 Expression in Hippocampus of Basolateral Amygdala (BLA) Electrical Kindled Epilepsy Rat

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Caspase-3 expression was determined in the hippocampus of electrically kindled rats with and without topiramate treatment. Bipolar electrotrodes were implanted for chronic stimulation of the basolateral amygdala (BLA) to achieve a kindled state. Seizure and behavioral responses were observed, and video-electroencephalograms were recorded during and after kindling. After topiramate treatment (80 mg/kg, p.o.), the hippocampi were extracted and caspase-3 mRNA analyzed by semiquantitative RT-PCR. Caspase-3 immunoreactivity was determined with immunohistochemical staining. Topiramate treatment resulted in a significant decrease in the mean duration of seizures from 52 s in kindled rats to 13 s. The after-discharge duration was significantly decreased by 70% after topiramate treatment. Significant upregulations of both caspase-3 mRNA and caspase-3 immunoreactivity were observed in the kindled rats. These kindling-mediated increases in caspase-3 were prevented by topiramate treatment, and these levels were not different from those of sham-operated controls. In BLA-kindled rats, mRNA and immunoreactivity for caspase-3 were increased. Treatment with topiramate prevented the kindling-associated increases in caspase-3 as well as the increases in seizure duration and after-discharge duration. These data suggest that topiramate may have a neuroprotective role in addition to its action as an anticonvulsant.

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Asprodini, E. K., Rainnie, D. G., Anderson, A. C., & Shinnick-Gallagher, P. (1992). In vivo kindling does not alter afterhyperpolarization (AHPs) following action potential firing in vitro in basolateral amygdala neurons. Brain Research, 588, 329–334.

    Article  PubMed  CAS  Google Scholar 

  • Bengzon, J., Mohapel, P., & Ekdahl, C. T. (2002). Neuronal apoptosis after brief and prolonged seizures. Progress in Brain Research, 135, 111–119.

    Article  PubMed  CAS  Google Scholar 

  • Biton, V., Montouris, G. D., Ritter, F., et al. (1999). A randomized, placebo-controlled study of topiramate in primary generalized tonic-clonic seizures. Neurology, 52, 1330–1337.

    PubMed  CAS  Google Scholar 

  • Cha, B. H., Silveira, D. C., Liu, X., Hu, Y., & Holmes, G. L. (2002). Effect of topiramate following recurrent and prolonged seizures during early development. Epilepsy Research, 51, 217–232.

    Article  PubMed  CAS  Google Scholar 

  • DeLorenzo, R. J., Morris, T. A., Blair, R. E., Wallace, M., & Razvi, B. (2002). Topiramate is both neuroprotective and antiepileptogenic in the pilocarpine model of status epilepticus. Epilepsia, 43(Suppl 7), S15.

    Google Scholar 

  • Edmonds Jr., H. L., Jiang, Y. D., Zhang, P. Y., & Shank, R. (2001). Topiramate as a neuroprotectant in a rat model of global ischemia-induced degeneration. Life Science, 69, 2265–2277.

    Article  CAS  Google Scholar 

  • Ekdahl, C. T., Mohapel, P., Weber, E., Bahr, B., Blomgren, K., & Lindvall, O. (2002). Caspase-mediated death of newly formed neurons in the adult rat dentate gyrus following status epilepticus. European Journal of Neuroscience, 16(8), 1463–1471.

    Article  PubMed  Google Scholar 

  • Elterman, R. D., Glauser, T. A., Wyllie, E., Reife, R., Wu, S.-C., Pledger, G., Topiramate, Y. P., & Study Group (1999). A double-blind, randomized trial of topiramate as adjunctive therapy for partial-onset seizures in children. Neurology, 52, 1338–1344.

    PubMed  CAS  Google Scholar 

  • Faherty, C. J., Xanthoudakis, S., & Smeyne, R. J. (1999). Caspase-3-dependent neuronal death in the hippocampus following kainic acid treatment. Molecular Brain Research, 70(1), 159–163.

    Article  PubMed  CAS  Google Scholar 

  • Fernandes-Alnemri, T., Litwack, G., & Alnemri, E. S. (1994). CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1ß-converting enzyme. Journal of Biological Chemistry, 269, 30761–30764.

    PubMed  CAS  Google Scholar 

  • Frisch, C., Kudin, A. P., Elger, C. E., Kunz, W. S., & Helmstaedter, C. (2007). Amelioration of water maze performance deficits by topiramate applied during pilocarpine-induced status epilepticus is negatively dose-dependent. Epilepsy Research, 73(2), 173–180.

    Article  PubMed  CAS  Google Scholar 

  • Gean, P. W., Shinnick-Gallagher, P., & Anderson, A. C. (1989). Spontaneous epileptiform activity and alteration of GABA- and of NMDA- mediated neurotransmission in amygdala neurons kindled in vivo. Brain Research, 494, 177–181.

    Article  PubMed  CAS  Google Scholar 

  • Gibbs 3rd, J. W., Sombati, S., DeLorenzo, R. J., & Coulter, D. A. (2000). Cellular actions of topiramate: blockade of kainate-evoked inward currents in cultured hippocampal neurons. Epilepsia, 41(Suppl 1), S10–S16.

    Article  PubMed  CAS  Google Scholar 

  • Glier, C., Dzietko, M., Bittigau, P., Jarosz, B., Korobowicz, E., & Ikonomidou, C. (2004). Therapeutic doses of topiramate are not toxic to the developing rat brain. Experimental Neurology, 187, 403–409.

    Article  PubMed  CAS  Google Scholar 

  • Guberman, A., Neto, W., Gassmann-Mayer, C., & EPAJ-119 Study Group (2002). Low-dose topiramate in adults with treatment-resistant partial-onset seizures. Acta Neurologica Scandinavica, 106, 183–189.

    Article  PubMed  CAS  Google Scholar 

  • Henshall, D. C., Chen, J., & Simon, R. P. (2000a). Involvement of caspase-3-like protease in the mechanism of cell death following focally evoked limbic seizures. Journal of Neurochemistry, 74(3), 1215–1223.

    Article  PubMed  CAS  Google Scholar 

  • Henshall, D. C., Clark, R. S., Adelson, P. D., Chen, M., Watkins, S. C., & Simon, R. P. (2000b). Alterations in bcl-2 and caspase gene family protein expression in human temporal lobe epilepsy. Neurology, 55(2), 250–257.

    PubMed  CAS  Google Scholar 

  • Holmes, K. H., Keele, N. B., & Shinnick-Gallagher, P. (1996). Loss of metabotropic glutamate receptor (mGluR)-mediated hyperpolarizations and increase in mGluR depolarizations in basolateral amygdala neurons in kindling-induced epilepsy. Journal of Neurophysiology, 76, 1208–1212.

    Google Scholar 

  • Kondratyev, A., Selby, D., & Gale, K. (2002). Status epilepticus leads to the degradation of the endogenous inhibitor of caspase-activated DNase in rats. Neuroscience Letters, 319, 145–148.

    Article  PubMed  CAS  Google Scholar 

  • Krajewska, M., Wang, H.-G., Krajewski, S., et al. (1997). Immunohistochemical analaysis of in vivo patterns of expression of CPP32 (Caspase-3), a cell death protease. Cancer Research, 57, 1605–1613.

    PubMed  CAS  Google Scholar 

  • Kudin, A. P., Debska-Vielhaber, G., Vielhaber, S., Elger, C. E., & Kunz, W. S. (2004). The mechanism of neuroprotection by topiramate in an animal model of epilepsy. Epilepsia, 45(12), 1478–1487.

    Article  PubMed  CAS  Google Scholar 

  • Löscher, W., Ebert, U., Wahnschaffe, U., & Rundfeldt, C. (1995). Susceptibility of different cell layers of the anterior and posterior part of the piriform cortex to electrical stimulation and kindling: comparison with the basolateral amygdala and "area tempestas. Neuroscience, 66, 265–276.

    Article  PubMed  Google Scholar 

  • Morimoto, K., Fahnestock, M., & Racine, R. J. (2004). Kindling and status epilepticus models of epilepsy: rewiring the brain. Progress in Neurobiology, 73(1), 1–60.

    Article  PubMed  CAS  Google Scholar 

  • Nicholson, D. W., Ambereen, A., Thornberry, N. A., et al. (1995). Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature, 376, 37–43.

    Article  PubMed  CAS  Google Scholar 

  • Noè, F., Pool, A. H., Nissinen, J., Gobbi, M., et al. (2008). Neuropeptide Y gene therapy decreases chronic spontaneous seizures in a rat model of temporal lobe epilepsy. Brain, 131(6), 1506–1515.

    Article  PubMed  Google Scholar 

  • Pitkanen, A. (2004). New pharmacotherapy for epilepsy. Idrugs, 7(5), 471–477.

    PubMed  Google Scholar 

  • Privitera, M. D., Brodie, M. J., Mattson, R. H., Chadwick, D. W., Neto, W., Wang, S., & EPMN 105 Study Group (2003). Topiramate, carbamazepine and valproate monotherapy: double-blind comparison in newly diagnosed epilepsy. Acta Neurologica Scandinavica, 107, 165–175.

    Article  PubMed  CAS  Google Scholar 

  • Racine, R. J. (1972). Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol, 32, 281–294.

    Article  PubMed  CAS  Google Scholar 

  • Rainnie, D. G., Asprodini, E. K., & Shinnick-Gallagher, P. (1992). Kindling-induced long-lasting changes in synaptic transmission in the basolateral amygdala. Journal of Neurophysiology, 67, 443–454.

    PubMed  CAS  Google Scholar 

  • Rigoulot, M. A., Koning, E., Ferrandon, A., & Nehlig, A. (2004). Neuroprotective properties of topiramate in the lithium-pilocarpine model of epilepsy. Journal of Pharmacology and Experimental Therapeutics, 308(2), 787–795.

    Article  PubMed  CAS  Google Scholar 

  • Sachdeo, R. C., Glauser, T. A., Ritter, F., Reife, R., Lim, P., Pledger, G., Topiramate, Y. L., & Study Group (1999). A double-blind, randomized trial of topiramate in Lennox-Gastaut syndrome. Neurology, 52, 1882–1887.

    PubMed  CAS  Google Scholar 

  • Sakurai, M., Nagata, T., Abe, K., Horinouchi, T., Itoyama, Y., & Tabayashi, K. (2003). Survival and death-promoting events after transient spinal cord ischemia in rabbits: Induction of Akt and caspase3 in motor neurons. Journal of Thoracic and Cardiovascular Surgery, 125, 370.

    Article  PubMed  CAS  Google Scholar 

  • Shank, R. P., Gardocki, J. F., Streeter, A. J., & Maryanoff, B. E. (2000). An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics and mechanisms of action. Epilepsia, 41(Suppl 1), S3–S9.

    Article  PubMed  CAS  Google Scholar 

  • Wang, P., Ren, R. N., Cai, S. Y., Chen, X. M., & Ye, L. Y. (2008). Neuroprotective effects of topiramate and folic acid on young rats with kindling-induced epilepsy. Zhongguo Dang Dai Er Ke Za Zhi, 10(1), 65–9.

    PubMed  Google Scholar 

  • White, H. S., Brown, S. D., Woodhead, J. H., Skeen, G. A., & Wolf, H. H. (2000). Topiramate modulates GABA-evoked currents in murine cortical neurons by a nonbenzodiazepine mechanism. Epilepsia, 41(Suppl 1), S17–S20.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, X., Velumian, A. A., Jones, O. T., & Carlen, P. L. (2000). Modulation of high-voltage-activated calcium channels in dentate granule cells by topiramate. Epilepsia, 41(Suppl 1), S52–S60.

    Article  PubMed  CAS  Google Scholar 

  • Zona, C., Ciotti, M. T., & Avoli, M. (1997). Topiramate attenuates voltage-gated sodium currents in rat cerebellar granule cells. Neurosci Lett, 231, 123–126.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

We would like to thank Drs. Douglas E. Brenneman and Illana Gozes for extensive editorial suggestions; Prof. Qizhang Yin and Shan Gong for technical assistance in model establishment; Dr. Xiaodong Wang for offering stimulator; and Dr. Xueming Zhu for advice with microscopy. This work was supported by the Medical Development Foundation of Suzhou University (2007) and Suzhou Social Development Foundation (No.SS08016) Xuqin Chen and Guanshui Bao contributed equally to this work.

Author information

Authors and Affiliations

  1. Department of Neurology, Children’s Hospital of Soochow University, No.303, Jingde Road, Suzhou, 215003, China

    Xuqin Chen, Yan Li & Zhedong Wang

  2. Institute of Medical Biotechnology, Soochow University, No.708, Renmin Road, Suzhou, 215007, China

    Xueguang Zhang

  3. Department of Neurology, No.3 People’s Hospital Affiliated to Shanghai Jiaotong University School of Medicine, No.280, Mohe Road, Shanghai, 201900, China

    Guanshui Bao

  4. Department of Pediatrics, Wuxi People’s Hospital, No.299, Qingyang Road, Wuxi, 214023, China

    Ying Hua

Authors
  1. Xuqin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guanshui Bao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ying Hua
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhedong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xueguang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Zhedong Wang or Xueguang Zhang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, X., Bao, G., Hua, Y. et al. The Effects of Topiramate on Caspase-3 Expression in Hippocampus of Basolateral Amygdala (BLA) Electrical Kindled Epilepsy Rat. J Mol Neurosci 38, 201–206 (2009). https://doi.org/10.1007/s12031-008-9173-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-008-9173-4

Keywords

Search

Navigation