title: Exposure to cerebrospinal fluid of sporadic amyotrophic lateral sclerosis patients alters Nav1.6 and Kv1.6 channel expression in rat spinal motor neurons.
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.
authors.affiliation: Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Post Box no: 2900, Hosur Road, Bangalore-560 029, India.
authors.forename: R
authors.initials: R
authors.lastname: Gunasekaran
authors.forename: R Sankara
authors.initials: RS
authors.lastname: Narayani
authors.forename: K
authors.initials: K
authors.lastname: Vijayalakshmi
authors.forename: Phalguni Anand
authors.initials: PA
authors.lastname: Alladi
authors.forename: K
authors.initials: K
authors.lastname: Shobha
authors.forename: A
authors.initials: A
authors.lastname: Nalini
authors.forename: T N
authors.initials: TN
authors.lastname: Sathyaprabha
authors.forename: T R
authors.initials: TR
authors.lastname: Raju
mesh_terms: 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
chemical_list: D001685:Biological Factors; D051667:Kv1.6 Potassium Channel; D015222:Sodium Channels