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

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.

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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.

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Authors

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.

Corresponding author

Correspondence to Fabio Rogerio.

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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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Mota, M.V.B., Zaidan, B.C., do Canto, A.M. et al. ATP Synthase Subunit Beta Immunostaining is Reduced in the Sclerotic Hippocampus of Epilepsy Patients. Cell Mol Neurobiol 39, 149–160 (2019). https://doi.org/10.1007/s10571-018-0641-2

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Keywords

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