Metabolic Brain Disease

, Volume 28, Issue 3, pp 387–396

Experimentally-induced Wernicke’s encephalopathy modifies crucial rat brain parameters: the importance of Na+,K+-ATPase and a potentially neuroprotective role for antioxidant supplementation

  • Apostolos Zarros
  • Charis Liapi
  • Hussam Al-Humadi
  • Marianna Almpani
  • Vasileios Stolakis
  • Nikolina Skandali
  • Konstantinos Voumvourakis
  • Eleni Katsouni
  • Stylianos Tsakiris
Original Paper

DOI: 10.1007/s11011-013-9394-2

Cite this article as:
Zarros, A., Liapi, C., Al-Humadi, H. et al. Metab Brain Dis (2013) 28: 387. doi:10.1007/s11011-013-9394-2

Abstract

Wernicke’s encephalopathy (WE) is a serious neuropsychiatric syndrome caused by chronic alcoholism and thiamine (T) deficiency. Our aim was to shed more light on the pathophysiology of WE, by introducing a modified in vivo experimental model of WE and by focusing on changes provoked in the total antioxidant status (TAS) and three crucial brain enzyme activities in adult rats. Rats were placed on ethanol (EtOH) consumption (20 % v/v) for a total of 5 weeks. By the end of the third week, rats were fed a T-deficient diet (TDD) and were treated with pyrithiamine (PT; 0.25 mg/kg) for the remaining 2 weeks. Following the induction of WE symptomatology, rats were treated with three consecutive (every 8 h) injections of saline or T (100 mg/kg) and were sacrificed. Brain homogenates were generated and used for spectrophotometrical evaluation of TAS and enzymatic activities. Additionally, in vitro experiments were conducted on brain homogenates or pure enzymes incubated with T or neuromodulatory antioxidants. Pre-exposure to EtOH provided a successful protocol modification that did not affect the expected time of WE symptomatology onset. Administration of T ameliorated this symptomatology. WE provoked oxidative stress that was partially limited by T administration, while T itself also caused oxidative stress to a smaller extent. Brain acetylcholinesterase (AChE) was found inhibited by WE and was further inhibited by T administration. In vitro experiments demonstrated a potential neuroprotective role for L-carnitine (Carn). Brain sodium-potassium adenosine triphosphatase (Na+,K+-ATPase) activity was found increased in WE and was reduced to control levels by in vivo T administration; this increase was also evident in groups exposed to PT or to TDD, but not to EtOH. In vitro experiments demonstrated a potential neuroprotective role for this Na+,K+-ATPase stimulation through T or L-cysteine (Cys) administration. Brain magnesium adenosine triphosphatase (Mg2+-ATPase) activity was found decreased by prolonged exposure to EtOH, but was not affected by the experimental induction of WE. Our data suggest that T administration inhibits AChE, which is also found inhibited in WE. Moreover, increased brain Na+,K+-ATPase activity could be a marker of T deficiency in WE, while combined T and antioxidant co-supplementation of Cys and/or Carn could be neuroprotective in terms of restoring the examined crucial brain enzyme activities to control levels.

Keywords

Wernicke’s encephalopathyAcetylcholinesteraseNa+,K+-ATPaseMg2+-ATPaseAntioxidants

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Apostolos Zarros
    • 1
    • 2
  • Charis Liapi
    • 2
  • Hussam Al-Humadi
    • 2
  • Marianna Almpani
    • 1
  • Vasileios Stolakis
    • 1
    • 2
  • Nikolina Skandali
    • 1
    • 2
  • Konstantinos Voumvourakis
    • 3
  • Eleni Katsouni
    • 1
    • 2
  • Stylianos Tsakiris
    • 1
  1. 1.Laboratory of Physiology, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
  2. 2.Laboratory of Pharmacology, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
  3. 3.2nd Department of NeurologyAttikon University Hospital, Medical School, National and Kapodistrian University of AthensAthensGreece