Exposure to cerebrospinal fluid of sporadic Amyotrophic Lateral Sclerosis patients alters Nav1.6 and Kv1.6 channel expression in rat spinal motor neurons
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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.