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Cellular and Molecular Neurobiology

, Volume 39, Issue 1, pp 149–160 | Cite as

ATP Synthase Subunit Beta Immunostaining is Reduced in the Sclerotic Hippocampus of Epilepsy Patients

  • Marcelo Vilas Boas Mota
  • Bruna Cunha Zaidan
  • Amanda Morato do Canto
  • Enrico Ghizoni
  • Helder Tedeschi
  • Luciano de Souza Queiroz
  • Marina K. M. Alvim
  • Fernando Cendes
  • Iscia Lopes-Cendes
  • André Almeida Schenka
  • André Schwambach Vieira
  • Fabio RogerioEmail author
Original Research
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Abstract

Epilepsy is a common disease presenting with recurrent seizures. Hippocampal sclerosis (HS) is the commonest histopathological alteration in patients with temporal lobe epilepsy (TLE) undergoing surgery. HS physiopathogenesis is debatable. We have recently studied, by using mass spectrometry-based proteomics, an experimental model of TLE induced by electrical stimulation. Specifically, protein expressions of both the beta subunit of mitochondrial ATP synthase (ATP5B) and of membrane ATPases were found to be reduced. Here, we investigated tissue distribution of ATP5B and sodium/potassium-transporting ATPase subunit alpha-3 (NKAα3), a protein associated with neuromuscular excitability disorders, in human hippocampi resected “en bloc” for HS treatment (n = 15). We used immunohistochemistry and the stained area was digitally evaluated (increase in binary contrast of microscopic fields) in the hippocampal sectors (CA1–CA4) and dentate gyrus. All HS samples were classified as Type 1, according to the International League Against Epilepsy (ILAE) 2013 Classification (predominant cell loss in CA1 and CA4). ATP5B was significantly decreased in all sectors and dentate gyrus of HS patients compared with individuals submitted to necropsy and without history of neurological alterations (n = 10). NKAα3 expression showed no difference. Moreover, we identified a negative correlation between frequency of pre-operative seizures and number of neurons in CA1. In conclusion, our data showed similarity between changes in protein expression in a model of TLE and individuals with HS. ATP5B reduction would be at least in part due to neuronal loss. Future investigations on ATP5B activity could provide insights into the process of such cell loss.

Keywords

Epilepsy Hippocampal sclerosis Proteomics Immunohistochemistry Mitochondrial ATP synthase Sodium/potassium ATPase 

Notes

Acknowledgements

This study was sponsored by grants from Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP; 2013/07559-3). The authors wish to thank Mr. Helymar C. Machado for helping with statistical analysis.

Author Contributions

MVBM, AMC, IL-C, ASV and FR contributed to study design. MVBM, BCZ, AMC, EG, HT, LSQ, MKMA, FC, IL-C, AAS, ASV and FR obtained and analyzed the data. MVBM, BCZ, IL-C, ASV and FR drafted the manuscript and figures.

Conflict of interest

Dr Iscia Lopes-Cendes was an ad-hoc specialist for Biomarin (Dec. 2017). The other authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Marcelo Vilas Boas Mota
    • 1
  • Bruna Cunha Zaidan
    • 1
  • Amanda Morato do Canto
    • 2
  • Enrico Ghizoni
    • 3
  • Helder Tedeschi
    • 3
  • Luciano de Souza Queiroz
    • 1
  • Marina K. M. Alvim
    • 3
  • Fernando Cendes
    • 3
  • Iscia Lopes-Cendes
    • 2
  • André Almeida Schenka
    • 4
  • André Schwambach Vieira
    • 5
  • Fabio Rogerio
    • 1
    Email author
  1. 1.Department of Anatomical Pathology, School of Medical SciencesUniversity of Campinas (UNICAMP)CampinasBrazil
  2. 2.Department of Medical Genetics, School of Medical SciencesUniversity of Campinas (UNICAMP)CampinasBrazil
  3. 3.Department of Neurology, School of Medical SciencesUniversity of Campinas (UNICAMP)CampinasBrazil
  4. 4.Department of Pharmacology, School of Medical SciencesUniversity of Campinas (UNICAMP)CampinasBrazil
  5. 5.Department of Structural and Functional Biology, Institute of BiologyUniversity of Campinas (UNICAMP)CampinasBrazil

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