Altered in-vitro and in-vivo expression of glial glutamate transporter-1 following exposure to cerebrospinal fluid of amyotrophic lateral sclerosis patients.
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'.
Shobha
K
K
Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Hosur Road, Bangalore-560 029, India.
Vijayalakshmi
K
K
Alladi
Phalguni Anand
PA
Nalini
A
A
Sathyaprabha
T N
TN
Raju
T R
TR
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
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