Selenothymidine protects against biochemical and behavioral alterations induced by ICV-STZ model of dementia in mice

Chem Biol Interact. 2018 Oct 1:294:135-143. doi: 10.1016/j.cbi.2018.08.004. Epub 2018 Aug 16.

Abstract

The present study evaluated the neuroprotective effects of one selenium-containing AZT derivative compound (S1073) in memory and learning impairment caused by Intracerebroventricular-streptozotocin (ICV-STZ). ICV-STZ in mice causes impairment of energy metabolism with oxidative damage and cholinergic dysfunction, and provides a relevant model for sporadic dementia of Alzheimer's type (AD). Acetylcolinesterase (AChE), Catalase (CAT), dichlorofluorescein oxidation (DCFH), TBARS and thiol content were measured. Swiss adult mice were pre-treated with S1073 [1 mmol/kg] (i.p.) and after 30 min of the injection received a bilateral dose of STZ [11.3 μmol/l]. After 8 days' STZ injection, we performed the behavioral experiments (Beaker test, Open field and Morris water maze task). ICV-STZ caused significant learning and memory impairments, which were significantly improved by S1073 pre-treatment. A significant increase in cerebral DFCH, TBARS levels and AChE activity and a disturbance in the memory and learning were observed in ICV-STZ injected animals. S1073 significantly ameliorated all alterations induced by ICV-STZ in mice. All these findings support the neuroprotective role of S1073 in mice model of Alzheimer's dementia-type induced by ICV-STZ, which may be associated with its antioxidant activity and/or with its inhibitory effect in brain AChE. In fact, in silico analysis indicated that S1073 may be an inhibitor of AChE.

Keywords: Alzheimer; Behavioral; Learning; Memory; Oxidative stress; Streptozotocin.

MeSH terms

  • Acetylcholinesterase / chemistry
  • Acetylcholinesterase / metabolism
  • Alzheimer Disease / chemically induced
  • Alzheimer Disease / prevention & control
  • Animals
  • Behavior, Animal / drug effects*
  • Binding Sites
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Catalase / metabolism
  • Catalytic Domain
  • Disease Models, Animal
  • Infusions, Intraventricular
  • Maze Learning / drug effects
  • Memory / drug effects
  • Mice
  • Molecular Docking Simulation
  • Neuroprotective Agents / metabolism
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Organoselenium Compounds / metabolism
  • Organoselenium Compounds / pharmacology*
  • Organoselenium Compounds / therapeutic use
  • Oxidative Stress / drug effects
  • Streptozocin
  • Zidovudine / analogs & derivatives*
  • Zidovudine / metabolism
  • Zidovudine / pharmacology*
  • Zidovudine / therapeutic use

Substances

  • Neuroprotective Agents
  • Organoselenium Compounds
  • Zidovudine
  • Streptozocin
  • Catalase
  • Acetylcholinesterase