Exposure to cerebrospinal fluid of sporadic amyotrophic lateral sclerosis patients alters Nav1.6 and Kv1.6 channel expression in rat spinal motor neurons

Brain Res. 2009 Feb 19;1255:170-9. doi: 10.1016/j.brainres.2008.11.099. Epub 2008 Dec 11.

Abstract

Cerebro Spinal Fluid (CSF) from patients with ALS has been documented to have a toxic effect on motor neurons both in vivo and in vitro. Here we show that the CSF from Amyotrophic Lateral Sclerosis (ALS) patients (ALS-CSF) has the potential to perturb ion channel expression, specifically the Na(v)1.6, and K(v)1.6 channels in newborn rat spinal motor neurons both in vivo and in vitro. ALS-CSF and CSF from nonALS patients (nonALS-CSF) were intrathecally injected into 3-day-old rat pups at the rate of 1 microl/2.5 min using a microinjector. In addition, embryonic rat spinal cord cultures were also exposed to 10% ALS or nonALS-CSF on the 9th day in vitro (9DIV) in serum free DMEM medium. After 48 h of CSF exposure, the cultures and the spinal cord sections were processed for immunostaining of the above mentioned ion channels. We observed a decrease in the expression of Na(v)1.6 and K(v)1.6 channels in motor neurons in ALS-CSF treated group, and the presence of trophic factors like Brain Derived Neurotrophic Factor (BDNF) and Ciliary Neurotrophic Factor CNTF partially reversed the effects produced by ALS-CSF. Altered expression of these voltage-gated channels may interfere with the electrical activity of motor neurons, and thereby lead to the degeneration of neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / metabolism*
  • Animals
  • Animals, Newborn
  • Biological Factors / cerebrospinal fluid
  • Biological Factors / toxicity*
  • Cells, Cultured
  • Cerebrospinal Fluid*
  • Gene Expression Regulation
  • Humans
  • Injections, Spinal
  • Kv1.6 Potassium Channel / metabolism*
  • Microinjections
  • Motor Neurons / drug effects*
  • Motor Neurons / metabolism
  • Rats
  • Rats, Wistar
  • Sodium Channels / metabolism*
  • Spinal Cord / cytology
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism

Substances

  • Biological Factors
  • Kv1.6 Potassium Channel
  • Sodium Channels