The effect of intrahippocampal beta amyloid (1-42) peptide injection on oxidant and antioxidant status in rat brain

Ann N Y Acad Sci. 2007 Apr;1100:510-7. doi: 10.1196/annals.1395.056.

Abstract

In some animal models, cognitive impairment and neurodegenerative disorders that mimic Alzheimer's disease (AD) can be reproduced by intracerebral or intracerebroventricular administration of peptide (Abeta) beta amyloid. Evidence suggests that oxidative stresses are involved in the mechanism of Abeta-induced neurotoxicity and AD pathogenesis. Exposure to Abeta increases lipid peroxidation, protein oxidation, and the formation of hydrogen peroxide in cultured cells. Nitric oxide (NO) has significant physiological roles in the central nervous system and also it can be implicated in neurodegenerative diseases because of its free radical properties. The purpose of this study is to search the effects of intrahippocampal Abeta (1-42) injection on malondialdehyde (MDA), glutathione (GSH), and nitrite plus nitrate (NOx) levels in temporal cortex and basal forebrain in rats. In this study, male adult Wistar albino rats were divided into two groups. Abeta (1-42) peptide (10 mug/2 muL) was administered bilaterally as a single injection into the hippocampal fissure by a Hamilton microsyringe. Distilled water was administered to the control group by using the same procedure. Ten days after the Abeta (1-42) injection, the rats were decapitated and brains were rapidly removed. MDA, GSH, and NOx levels were analyzed spectrophotometrically in temporal cortex and basal forebrain. MDA levels and NOx were increased 10 days after the injection of Abeta (1-42) in temporal cortex and basal forebrain, but no statistical significance was found compared to control group. However, GSH levels were significantly higher in temporal cortex and basal forebrain in the Abeta (1-42)-injected group than the control group (P < 0.05). In conclusion, increased levels of GSH in temporal cortex and basal forebrain after the intrahippocampal Abeta (1-42) injection show that a protective mechanism might develop due to oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / administration & dosage
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Antioxidants / metabolism*
  • Brain / metabolism*
  • Glutathione / metabolism
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Humans
  • Male
  • Malondialdehyde / pharmacology
  • Nitric Oxide / metabolism
  • Oxidants / metabolism
  • Oxidative Stress
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / metabolism*
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Rats
  • Rats, Wistar

Substances

  • Amyloid beta-Peptides
  • Antioxidants
  • Oxidants
  • Peptide Fragments
  • Peptides
  • amyloid beta-protein (1-42)
  • Nitric Oxide
  • Malondialdehyde
  • Glutathione