Cognitive deficits induced by combined exposure of stress and alcohol mediated through oxidative stress-PARP pathway in the hippocampus

Neurosci Lett. 2017 Jul 13:653:208-214. doi: 10.1016/j.neulet.2017.05.058. Epub 2017 May 30.

Abstract

Several studies reported that stress can enhance the consumption of alcohol in humans and animals. However, the combinatorial effect of stress and alcohol on cognitive function and neurochemical alterations is quite understudied. In the present study, we have elucidated the involvement of oxidative stress-PARP cascade in alcohol and restraint stress (RS)-exposed animals using a PARP inhibitor, 1,5-isoquinolinediol (3mg/kg for 14days). Male Swiss albino mice were given alcohol (ALC) or RS (2h per day) or both in ALC+RS group for 28days. Behavioral analysis revealed cognitive dysfunction in ALC+RS group. Furthermore, oxidative stress and raised level of pro-inflammatory cytokines were found in the hippocampus region of ALC+RS group. Semi-quantitative reverse transcriptase PCR showed overactivation of PARP-1 gene in ALC+RS group. 1,5-isoquinolinediol treatment significantly prevented cognitive deficits and aforementioned neurochemical alterations. Overall, our findings showed that ALC+RS exerted deleterious effects on the hippocampus which involves oxidative stress-PARP overactivation cascade.

Keywords: Alcohol; Memory; Oxidative stress; PARP; Restraint stress.

MeSH terms

  • Animals
  • Cognitive Dysfunction / chemically induced
  • Cognitive Dysfunction / enzymology
  • Cognitive Dysfunction / etiology*
  • Encephalitis / complications
  • Encephalitis / metabolism
  • Ethanol / administration & dosage*
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Hippocampus / physiopathology
  • Interleukin-1beta / metabolism
  • Male
  • Mice
  • Oxidative Stress*
  • Poly (ADP-Ribose) Polymerase-1 / antagonists & inhibitors
  • Poly (ADP-Ribose) Polymerase-1 / metabolism*
  • Poly(ADP-ribose) Polymerase Inhibitors / administration & dosage
  • Restraint, Physical
  • Stress, Psychological / complications
  • Stress, Psychological / metabolism*

Substances

  • Interleukin-1beta
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Ethanol
  • Parp1 protein, mouse
  • Poly (ADP-Ribose) Polymerase-1