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

Gunasekaran, R. ; Sankara Narayani, R. ; Vijayalakshmi, K. ; Anand Alladi, Phalguni ; Shobha, K. ; Nalini, A. ; Sathyaprabha, T. N. ; Raju, T. R. (2009) Exposure to cerebrospinal fluid of sporadic amyotrophic lateral sclerosis patients alters Nav1.6 and Kv1.6 channel expression in rat spinal motor neurons Brain Research, 1255 . pp. 170-179. ISSN 0006-8993

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Official URL: http://linkinghub.elsevier.com/retrieve/pii/S00068...

Related URL: http://dx.doi.org/10.1016/j.brainres.2008.11.099

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 Nav1.6, and Kv1.6 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 μl/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 Nav1.6 and Kv1.6 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.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
Keywords:Spinal Motor Neuron; ALS-CSF; Nav1; 6 Sodium and Kv1; 6 Potassium Channel; BDNF; CNTF; Immunocytochemistry
ID Code:38509
Deposited On:23 May 2011 14:33
Last Modified:23 May 2011 14:33

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