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

Author(s):Show less -

Boas Mota, Marcelo Vilas ^[1] ; Zaidan, Bruna Cunha ^[1] ; do Canto, Amanda Morato ^[2] ; Ghizoni, Enrico ^[3] ; Tedeschi, Helder ^[3] ; Queiroz, Luciano de Souza ^[1] ; Alvim, Marina K. M. ^[3] ; Cendes, Fernando ^[3] ; Lopes-Cendes, Iscia ^[2] ; Schenka, Andre Almeida ^[4] ; Vieira, Andre Schwambach ^[5] ; Rogerio, Fabio ^[1]

Affiliation

^[1] Univ Campinas UNICAMP, Sch Med Sci, Dept Anat Pathol, Ave Tessalia de Vieira Camargo 126, BR-13083887 Campinas, SP - Brazil

^[2] Univ Campinas UNICAMP, Sch Med Sci, Dept Med Genet, Ave Tessalia de Vieira Camargo 126, BR-13083887 Campinas, SP - Brazil

^[3] Univ Campinas UNICAMP, Sch Med Sci, Dept Neurol, Ave Tessalia de Vieira Camargo 126, BR-13083887 Campinas, SP - Brazil

^[4] Univ Campinas UNICAMP, Sch Med Sci, Dept Pharmacol, Ave Tessalia de Vieira Camargo 126, BR-13083887 Campinas, SP - Brazil

^[5] Univ Campinas UNICAMP, Inst Biol, Dept Struct & Funct Biol, R Monteiro Lobato 255, BR-13083852 Campinas, SP - Brazil

• Document type: Journal article
• Source: Cellular and Molecular Neurobiology; v. 39, n. 1, p. 149-160, JAN 2019.
• Web of Science Citations: 1

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 (NKA3), 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). NKA3 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. (AU)

• FAPESP's process: 13/07559-3 - BRAINN - The Brazilian Institute of Neuroscience and Neurotechnology
• Grantee: Fernando Cendes
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC