Blocking of L-type calcium channels protects hippocampal and nigral neurons against iron neurotoxicity. The role of L-type calcium channels in iron-induced neurotoxicity

Int J Neurosci. 2013 Dec;123(12):876-82. doi: 10.3109/00207454.2013.813510. Epub 2013 Jul 15.

Abstract

Iron plays an important role in maintaining normal brain function. However, iron overload and enhanced hydroxyl radical formation have been implicated as the causative factors of some neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. Calcium is also required for diverse physiological process including secretion of neurotransmitters, synaptic plasticity, gene expression and axonal growth. Iron and calcium are essential for neuronal function but, when present in excessive level, they induce neuronal damage and may even cause neuronal death. Some reports suggest that voltage gated calcium channels (VGCCs) are an alternate route for iron entry into neuronal cell lines under conditions of iron overload. The aim of the present study was to investigate the effects of L-type VGCCs on iron-induced neurotoxicity. Iron neurotoxicity was generated by intracerebroventricular FeCl₃ injection. Nicardipine treatment (10 mg/kg/d) was applied to block L-type VGCCs for 10 d. Rats were perfused intracardially under deep urethane anaesthesia after treatment period. Removed brains were processed using the standard histological techniques. The numbers of neurons in hippocampus and substantia nigra of all rats were estimated by stereological techniques. Results of present study show that nicardipine decreased hippocampal and nigral neuron loss from 43.9% to 18.4% and 41.0% to 12.1%, respectively. Outcomes of the present study propose that blocking of L-type VGCCs may reduce the neurotoxic effects of iron by inhibiting the cellular influx of excessive calcium and/or iron ions.

MeSH terms

  • Animals
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels, L-Type / metabolism*
  • Cell Count
  • Disease Models, Animal
  • Hippocampus / pathology*
  • Iron / metabolism
  • Iron / toxicity
  • Male
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurotoxicity Syndromes / drug therapy
  • Neurotoxicity Syndromes / etiology
  • Neurotoxicity Syndromes / pathology*
  • Nicardipine / pharmacology*
  • Rats
  • Rats, Wistar
  • Stereotaxic Techniques
  • Substantia Nigra / pathology*

Substances

  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Nicardipine
  • Iron