Cholinergic receptor blockade by scopolamine and mecamylamine exacerbates global cerebral ischemia induced memory dysfunction in C57BL/6J mice

Nitric Oxide. 2014 Dec 1:43:62-73. doi: 10.1016/j.niox.2014.08.009. Epub 2014 Aug 25.

Abstract

Global cerebral ischemia/reperfusion (GCI/R) injury encompasses complex pathophysiological sequalae, inducing loss of hippocampal neurons and behavioural deficits. Progressive neuronal death and memory dysfunctions culminate from several different mechanisms like oxidative stress, excitotoxicity, neuroinflammation and cholinergic hypofunction. Experimental evidences point to the beneficial effects of cholinomimetic agents such as rivastigmine and galantamine in improving memory outcomes following GCI/R injury. However, the direct implications of muscarinic and nicotinic receptor blockade during global cerebral ischemia/reperfusion injury have not been investigated. Therefore, we evaluated the relative involvement of muscarinic and nicotinic receptors in spatial/associative memory functions and neuronal damage during global cerebral ischemia reperfusion injury. The outcomes of present study support the idea that preservation of both muscarinic and nicotinic receptor functions is essential to alleviate hippocampal neuronal death in CA1 region following global cerebral ischemia/reperfusion injury.

Keywords: Global cerebral ischemia; Hippocampus; Mecamylamine; Memory dysfunction; Muscarinic receptor; Nicotinic receptor; Scopolamine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Brain Ischemia / complications*
  • Brain Ischemia / physiopathology
  • Choline O-Acetyltransferase / metabolism
  • Cholinergic Antagonists / pharmacology*
  • Male
  • Mecamylamine / pharmacology*
  • Memory Disorders / chemically induced
  • Memory Disorders / etiology*
  • Memory Disorders / physiopathology
  • Mice
  • Mice, Inbred C57BL
  • Neurons / drug effects*
  • Receptors, Cholinergic / metabolism
  • Reperfusion Injury / chemically induced
  • Reperfusion Injury / etiology
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control
  • Scopolamine / pharmacology*

Substances

  • Cholinergic Antagonists
  • Receptors, Cholinergic
  • Mecamylamine
  • Scopolamine
  • Choline O-Acetyltransferase
  • Acetylcholinesterase