Nerolidol-loaded nanospheres prevent behavioral impairment via ameliorating Na+, K+-ATPase and AChE activities as well as reducing oxidative stress in the brain of Trypanosoma evansi-infected mice

Naunyn Schmiedebergs Arch Pharmacol. 2017 Feb;390(2):139-148. doi: 10.1007/s00210-016-1313-8. Epub 2016 Nov 2.

Abstract

The aim of this study was to investigate the effect of nerolidol-loaded nanospheres (N-NS) on the treatment of memory impairment caused by Trypanosoma evansi in mice, as well as oxidative stress, and Na+, K+-ATPase and acetylcholinesterase (AChE) activities in brain tissue. Animals were submitted to behavioral tasks (inhibitory avoidance task and open-field test) 4 days postinfection (PI). Reactive oxygen species (ROS) and thiobarbituric acid-reactive substance (TBARS) levels and catalase (CAT), superoxide dismutase (SOD), Na+, K+-ATPase and AChE activities were measured on the fifth-day PI. T. evansi-infected mice showed memory deficit, increased ROS and TBARS levels and SOD and AChE activities, and decreased CAT and Na+, K+-ATPase activities compared to uninfected mice. N-NS prevented memory impairment and oxidative stress parameters (except SOD activity), while free nerolidol (N-F) restored only CAT activity. Also, N-NS treatment was able to prevent alterations in Na+, K+-ATPase and AChE activities caused by T. evansi infection. A significantly negative correlation was observed between memory and ROS production (p < 0.001; r = -0.941), as well as between memory and AChE activity (p < 0.05; r = -0.774). On the contrary, a significantly positive correlation between memory and Na+, K+-ATPase activity was observed (p < 0.01; r = 0.844). In conclusion, N-NS was able to reverse memory impairment and to prevent increased ROS and TBARS levels due to amelioration of Na+, K+-ATPase and AChE activities and to activation of the antioxidant enzymes, respectively. These results suggest that N-NS treatment may be a useful strategy to treat memory dysfunction and oxidative stress caused by T. evansi infection.

Keywords: Antioxidant enzymes; Cognitive impairment; Nanomedicine; Trypanosomosis.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Antioxidants / administration & dosage*
  • Avoidance Learning / drug effects
  • Behavior, Animal / drug effects*
  • Brain / drug effects*
  • Brain / enzymology
  • Brain / pathology
  • Catalase / metabolism
  • Central Nervous System Protozoal Infections / drug therapy*
  • Central Nervous System Protozoal Infections / enzymology
  • Central Nervous System Protozoal Infections / parasitology
  • Central Nervous System Protozoal Infections / psychology
  • Cholinesterase Inhibitors / administration & dosage*
  • Cognition Disorders / drug therapy
  • Cognition Disorders / enzymology
  • Cognition Disorders / parasitology
  • Cognition Disorders / psychology
  • Disease Models, Animal
  • Female
  • GPI-Linked Proteins / antagonists & inhibitors
  • GPI-Linked Proteins / metabolism
  • Memory / drug effects
  • Memory Disorders / drug therapy
  • Memory Disorders / enzymology
  • Memory Disorders / parasitology
  • Memory Disorders / psychology
  • Mice
  • Motor Activity / drug effects
  • Nanospheres*
  • Nootropic Agents / administration & dosage
  • Oxidative Stress / drug effects*
  • Reaction Time / drug effects
  • Reactive Oxygen Species / metabolism
  • Sesquiterpenes / administration & dosage*
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors*
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Superoxide Dismutase / metabolism
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Trypanosoma / pathogenicity*
  • Trypanosomiasis / drug therapy*
  • Trypanosomiasis / enzymology
  • Trypanosomiasis / parasitology
  • Trypanosomiasis / psychology

Substances

  • Antioxidants
  • Cholinesterase Inhibitors
  • GPI-Linked Proteins
  • Nootropic Agents
  • Reactive Oxygen Species
  • Sesquiterpenes
  • Thiobarbituric Acid Reactive Substances
  • Catalase
  • Superoxide Dismutase
  • Acetylcholinesterase
  • Ache protein, mouse
  • Sodium-Potassium-Exchanging ATPase
  • nerolidol