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Neurofilament Phosphorylation is Increased in Ventral Horn Neurons of Neonatal Rat Spinal Cord Exposed to Cerebrospinal Fluid from patients with Amyotrophic Lateral Sclerosis
Institution:1. Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore, 560 029, India;2. Department of Neurology, National Institute of Mental Health and Neuro Sciences, Bangalore, 560 029, India;1. Laboratory of Molecular Cell Biology, School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan;2. Laboratory of Toxicology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikigorikita, Tondabayashi, Osaka 584-8540, Japan;3. Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 7-2-1 Kamiohno, Himeji 670-8524 Japan;1. Department of Bioengineering, University of Colorado – Anschutz Medical Campus, Aurora, CO, USA;2. Department of Neurology, University of Colorado – Anschutz Medical Campus, Aurora, CO, USA;3. Department of Cell and Developmental Biology, University of Colorado – Anschutz Medical Campus, Aurora, CO, USA;1. Institute of Microbial Chemistry (BIKAKEN), Tokyo, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan;2. Institute of Medical Genetics, Tokyo Women’s Medical University, 10-22 Kawadacho, Shinjyuku-ku, Tokyo 162-0054, Japan;3. Merck Millipore Merck Ltd., Arco Tower 5F, 1-8-1 Shimomeguro, Megro-ku, Tokyo 153-8927, Japan;1. Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 7-2-1 Kamiohno, Himeji 670-8524, Japan;2. Department of Life Sciences Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, Kobe 650-8586, Japan;1. Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China;2. Department of Spinal Surgery, Second Affiliated Hospital of Luohe Medical College, Luohe, China
Abstract:Aberrant neurofilament (NF) phosphorylation in the soma of the ventral horn neurons of neo-natal rat spinal cord is observed following exposure to cerebrospinal fluid (CSF) of patients suffering from Amyotrophic Lateral Sclerosis (ALS). CSF samples from ALS and non-ALS neurological patients were injected into the spinal subarachnoid space of 3 day old rat pups. After 48 h, sections of spinal cords were stained for the presence of phosphorylated NF epitopes with SMI-31 antibody. The number of neuronal soma staining with this antibody in the ventral and dorsal horns sides of the spinal cord was counted. There was a significant 3-fold increase in the number of soma stained with SMI-31 antibody in the ventral horns of rat spinal cords exposed to CSF of patients with ALS compared to cords from rats exposed to CSF of non-ALS patients and those which were not exposed to any CSF samples. Such an increase in staining of neuronal soma was not observed in the dorsal horns. Hyperphosphorylation of neuronal soma suggests an initial stage of degenerative changes occurring in the motor (ventral horn) neurons following exposure to circulating factor(s) in the CSF of patients with ALS.
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