title: Altered in-vitro and in-vivo expression of glial glutamate transporter-1 following exposure to cerebrospinal fluid of amyotrophic lateral sclerosis patients.
abstract: Our earlier studies have shown that cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients causes death of motor neurons, both in in-vitro as well as in-vivo. There was an aberrant phosphorylation of neurofilaments in cultured spinal cord neurons of chick and rats following exposure to CSF of ALS patients (ALS-CSF). Other features of neurodegeneration, such as swollen neuronal soma and beading of neurites were also observed. In neonatal rat pups exposed to ALS-CSF, we observed phosphorylated neurofilaments in the soma of spinal motor neurons in addition to the increased lactate dehydrogenase activity and reactive astrogliosis. The present study examines the effect of ALS-CSF on the expression of glial glutamate transporter (GLT-1) in embryonic rat spinal cord cultures as well as in spinal astrocytes of neonatal rats. Immunostaining suggested a decrease in the expression of GLT-1 by astrocytes both in culture and in-vivo following exposure to ALS-CSF. Quantification of Western blots confirmed the decreased expression of GLT-1. Our results provide evidence that toxic factor(s) present in ALS-CSF depletes GLT-1 expression. This could lead to an increased level of glutamate in the synaptic pool causing excitotoxicity to motor neurons, possibly by triggering the 'glutamate-mediated toxicity-pathway'.
authors.affiliation: Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Hosur Road, Bangalore-560 029, India.
authors.forename: K
authors.initials: K
authors.lastname: Shobha
authors.forename: K
authors.initials: K
authors.lastname: Vijayalakshmi
authors.forename: Phalguni Anand
authors.initials: PA
authors.lastname: Alladi
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 / Q000134:cerebrospinal fluid*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001685:Biological Factors / Q000134:cerebrospinal fluid / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002555:Cerebrospinal Fluid; D004791:Enzyme Inhibitors / Q000494:pharmacology; D027342:Excitatory Amino Acid Transporter 2 / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007278:Injections, Spinal; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009498:Neurotoxins / Q000134:cerebrospinal fluid; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D001685:Biological Factors; D004791:Enzyme Inhibitors; D027342:Excitatory Amino Acid Transporter 2; D009498:Neurotoxins; D018698:Glutamic Acid; D007770:L-Lactate Dehydrogenase; D019331:NG-Nitroarginine Methyl Ester