The effects of lipoic acid on redox status in brain regions and systemic circulation in streptozotocin-induced sporadic Alzheimer's disease model

Metab Brain Dis. 2017 Aug;32(4):1017-1031. doi: 10.1007/s11011-017-9983-6. Epub 2017 Mar 15.

Abstract

While the deterioration of insulin-glucose metabolism (IGM), impaired redox homeostasis (IRH), β-amyloid accumulation was reported in Sporadic Alzheimer's Disease (SAD) model, aforementioned factors related to lipoic acid administration and anthropometric indexes (AIs) are not yet studied with integrative approach. β-amyloid accumulation, redox homeostasis biomarkers and AIs are investigated in SAD model. Streptozotocin-induced inhibition of insulin-signaling cascade but not GLUT-2 and GLUT-3 transporters takes a role in β-amyloid accumulation. Inhibition types are related to IRH in cortex, hippocampus and systemic circulation. Lipoic acid (LA) shows both antioxidant and prooxidant effect according to the anatomical location. LA administration also leads to improved AIs during GLUT-2 inhibition and cortical redox status in GLUT-3 inhibited group. Optimal LA action could be possible if its redox behavior is balanced to antioxidant effect. Diagnostic usage of systemic IRH parameters as biomarkers and their possible correlations with deteriorated IGM should be investigated. Graphical abstract ᅟ.

Keywords: Anthropometric indexes; Insulin-glucose metabolism; Lipoic acid; Oxidative stress; Sporadic Alzheimer’s disease model; β-amyloid accumulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Antioxidants / pharmacology*
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism
  • Disease Models, Animal
  • Glucose Transporter Type 2 / metabolism
  • Glucose Transporter Type 3 / metabolism
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Oxidation-Reduction
  • Oxidative Stress / drug effects*
  • Streptozocin
  • Thioctic Acid / pharmacology*

Substances

  • Amyloid beta-Peptides
  • Antioxidants
  • Glucose Transporter Type 2
  • Glucose Transporter Type 3
  • Streptozocin
  • Thioctic Acid