Antiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron overload

Transl Psychiatry. 2018 Sep 3;8(1):176. doi: 10.1038/s41398-018-0232-5.

Abstract

Iron accumulation in the brain has been recognized as a common feature of both normal aging and neurodegenerative diseases. Cognitive dysfunction has been associated to iron excess in brain regions in humans. We have previously described that iron overload leads to severe memory deficits, including spatial, recognition, and emotional memory impairments in adult rats. In the present study we investigated the effects of neonatal iron overload on proteins involved in apoptotic pathways, such as Caspase 8, Caspase 9, Caspase 3, Cytochrome c, APAF1, and PARP in the hippocampus of adult rats, in an attempt to establish a causative role of iron excess on cell death in the nervous system, leading to memory dysfunction. Cannabidiol (CBD), the main non-psychotropic component of Cannabis sativa, was examined as a potential drug to reverse iron-induced effects on the parameters analyzed. Male rats received vehicle or iron carbonyl (30 mg/kg) from the 12th to the 14th postnatal days and were treated with vehicle or CBD (10 mg/kg) for 14 days in adulthood. Iron increased Caspase 9, Cytochrome c, APAF1, Caspase 3 and cleaved PARP, without affecting cleaved Caspase 8 levels. CBD reversed iron-induced effects, recovering apoptotic proteins Caspase 9, APAF1, Caspase 3 and cleaved PARP to the levels found in controls. These results suggest that iron can trigger cell death pathways by inducing intrinsic apoptotic proteins. The reversal of iron-induced effects by CBD indicates that it has neuroprotective potential through its anti-apoptotic action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis / drug effects*
  • Cannabidiol / pharmacology*
  • Cognitive Dysfunction / chemically induced
  • Cognitive Dysfunction / drug therapy*
  • Disease Models, Animal
  • Hippocampus / drug effects
  • Hippocampus / pathology*
  • Iron / toxicity
  • Iron Compounds / toxicity
  • Iron Overload / physiopathology*
  • Male
  • Memory Disorders / chemically induced
  • Memory Disorders / prevention & control*
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects

Substances

  • Iron Compounds
  • Cannabidiol
  • iron pentacarbonyl
  • Iron