Quercetin prevents chronic unpredictable stress induced behavioral dysfunction in mice by alleviating hippocampal oxidative and inflammatory stress

Physiol Behav. 2017 Mar 15:171:69-78. doi: 10.1016/j.physbeh.2017.01.006. Epub 2017 Jan 7.

Abstract

It is now evident that chronic stress is associated with anxiety, depression and cognitive dysfunction and very few studies have focused on identifying possible methods to prevent these stress-induced disorders. Previously, we identified abundance of quercetin in Urtica dioica extract, which efficiently attenuated stress related complications. Therefore, current study was designed to investigate the effect of quercetin on chronic unpredicted stress (CUS) induced behavioral dysfunction, oxidative stress and neuroinflammation in the mouse hippocampus. Animals were subjected to unpredicted stress for 21days, during which 30mg/kg quercetin was orally administered to them. Effect of CUS and quercetin treatment on animal behavior was assessed between day 22-26. Afterward, the hippocampus was processed to evaluate neuronal damage, oxidative and inflammatory stress. Results revealed that stressed animals were highly anxious (Elevated Plus Maze and Open Field), showed depressive-like behavior (sucrose preference task), performed poorly in short-term and long-term associative memory task (passive avoidance step-through task) and displayed reduced locomotion (open field). Quercetin alleviated behavioral dysfunction in chronically stressed animals. Compared to CUS, quercetin treatment significantly reduced anxiety, attenuated depression, improved cognitive dysfunction and normalized locomotor activity. Further, CUS elevated the levels of oxidative stress markers (TBARS, nitric oxide), lowered antioxidants (total thiol, catalase), enhanced expression of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β and COX-2) in the hippocampus and damaged hippocampal neurons. Quercetin treatment significantly lowered oxidative and inflammatory stress and prevented neural damage. In conclusion, quercetin can efficiently prevent stress induced neurological complications by rescuing brain from oxidative and inflammatory stress.

Keywords: Antioxidant; Anxiety; Cognition; Depression; Quercetin; Stress.

MeSH terms

  • Animals
  • Antioxidants / therapeutic use*
  • Avoidance Learning / drug effects
  • Catalase / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Exploratory Behavior / drug effects
  • Food Preferences / drug effects
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Maze Learning / drug effects
  • Mental Disorders / etiology
  • Mental Disorders / prevention & control*
  • Mice
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects*
  • Quercetin / therapeutic use*
  • RNA, Messenger / metabolism
  • Stress, Psychological / complications
  • Time Factors

Substances

  • Antioxidants
  • Cytokines
  • RNA, Messenger
  • Nitric Oxide
  • Quercetin
  • Catalase