Exposure to cerebrospinal fluid of sporadic amyotrophic lateral sclerosis patients alters Nav1.6 and Kv1.6 channel expression in rat spinal motor neurons.
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.
Gunasekaran
R
R
Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Post Box no: 2900, Hosur Road, Bangalore-560 029, India.
Narayani
R Sankara
RS
Vijayalakshmi
K
K
Alladi
Phalguni Anand
PA
Shobha
K
K
Nalini
A
A
Sathyaprabha
T N
TN
Raju
T R
TR
D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001685:Biological Factors / Q000134:cerebrospinal fluid / Q000633:toxicity*; D002478:Cells, Cultured; D002555:Cerebrospinal Fluid; D005786:Gene Expression Regulation; D006801:Humans; D007278:Injections, Spinal; D051667:Kv1.6 Potassium Channel / Q000378:metabolism*; D008845:Microinjections; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D001685:Biological Factors; D051667:Kv1.6 Potassium Channel; D015222:Sodium Channels