PMID- 19109933 OWN - NLM STAT- MEDLINE DCOM- 20090318 LR - 20090203 IS - 1872-6240 (Electronic) IS - 0006-8993 (Linking) VI - 1255 DP - 2009 Feb 19 TI - Exposure to cerebrospinal fluid of sporadic amyotrophic lateral sclerosis patients alters Nav1.6 and Kv1.6 channel expression in rat spinal motor neurons. PG - 170-9 LID - 10.1016/j.brainres.2008.11.099 [doi] AB - 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. FAU - Gunasekaran, R AU - Gunasekaran R AD - Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Post Box no: 2900, Hosur Road, Bangalore-560 029, India. FAU - Narayani, R Sankara AU - Narayani RS FAU - Vijayalakshmi, K AU - Vijayalakshmi K FAU - Alladi, Phalguni Anand AU - Alladi PA FAU - Shobha, K AU - Shobha K FAU - Nalini, A AU - Nalini A FAU - Sathyaprabha, T N AU - Sathyaprabha TN FAU - Raju, T R AU - Raju TR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20081211 PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Biological Factors) RN - 0 (Kv1.6 Potassium Channel) RN - 0 (Sodium Channels) SB - IM MH - Amyotrophic Lateral Sclerosis/*metabolism MH - Animals MH - Animals, Newborn MH - Biological Factors/cerebrospinal fluid/*toxicity MH - Cells, Cultured MH - *Cerebrospinal Fluid MH - Gene Expression Regulation MH - Humans MH - Injections, Spinal MH - Kv1.6 Potassium Channel/*metabolism MH - Microinjections MH - Motor Neurons/*drug effects/metabolism MH - Rats MH - Rats, Wistar MH - Sodium Channels/*metabolism MH - Spinal Cord/cytology/drug effects/metabolism EDAT- 2008/12/27 09:00 MHDA- 2009/03/19 09:00 CRDT- 2008/12/27 09:00 PHST- 2008/09/12 00:00 [received] PHST- 2008/11/26 00:00 [revised] PHST- 2008/11/26 00:00 [accepted] PHST- 2008/12/27 09:00 [entrez] PHST- 2008/12/27 09:00 [pubmed] PHST- 2009/03/19 09:00 [medline] AID - S0006-8993(08)02900-4 [pii] AID - 10.1016/j.brainres.2008.11.099 [doi] PST - ppublish SO - Brain Res. 2009 Feb 19;1255:170-9. doi: 10.1016/j.brainres.2008.11.099. Epub 2008 Dec 11.