Na+, K+-ATPase activity in children with autism spectrum disorder: Searching for the reason(s) of its decrease in blood cells

Bolotta Alessandra, Visconti Paola, Fedrizzi Giorgio, Ghezzo Alessandro, Marini Marina, Manunta Paolo, Messaggio Elisabetta, Posar Annio, Vignini Arianna, Provvidenza Maria Abruzzo

Research output: Contribution to journalArticle

Abstract

Na+, K+-ATPase (NKA) activity, which establishes the sodium and potassium gradient across the cell membrane and is instrumental in the propagation of the nerve impulses, is altered in a number of neurological and neuropsychiatric disorders, including autism spectrum disorders (ASD). In the present work, we examined a wide range of biochemical and cellular parameters in the attempt to understand the reason(s) for the severe decrease in NKA activity in erythrocytes of ASD children that we reported previously. NKA activity in leukocytes was found to be decreased independently from alteration in plasma membrane fluidity. The different subunits were evaluated for gene expression in leukocytes and for protein expression in erythrocytes: small differences in gene expression between ASD and typically developing children were not apparently paralleled by differences in protein expression. Moreover, no gross difference in erythrocyte plasma membrane oxidative modifications was detectable, although oxidative stress in blood samples from ASD children was confirmed by increased expression of NRF2 mRNA. Interestingly, gene expression of some NKA subunits correlated with clinical features. Excess inhibitory metals or ouabain-like activities, which might account for NKA activity decrease, were ruled out. Plasma membrane cholesterol, but not phosphatidylcholine and phosphatidlserine, was slighty decreased in erythrocytes from ASD children. Although no compelling results were obtained, our data suggest that alteration in the erytrocyte lipid moiety or subtle oxidative modifications in NKA structure are likely candidates for the observed decrease in NKA activity. These findings are discussed in the light of the relevance of NKA in ASD. Autism Research 2018.

Original languageEnglish
JournalAutism Research
DOIs
Publication statusAccepted/In press - Jan 1 2018

Keywords

  • autism spectrum disorders
  • beta-actin
  • endogenous ouabain
  • erythrocyte membrane
  • membrane lipids
  • metals
  • Na, K-ATPase
  • NRF2
  • oxidative stress

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Genetics(clinical)

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    Alessandra, B., Paola, V., Giorgio, F., Alessandro, G., Marina, M., Paolo, M., Elisabetta, M., Annio, P., Arianna, V., & Abruzzo, P. M. (Accepted/In press). Na+, K+-ATPase activity in children with autism spectrum disorder: Searching for the reason(s) of its decrease in blood cells. Autism Research. https://doi.org/10.1002/aur.2002