Abstract
Amyotrophic lateral sclerosis (ALS), a neurodegenerative disease, is characterized by degeneration of lower and upper motor neurons. Serum and cerebrospinal fluid (CSF) of ALS patients have been found to exert toxic effects on neurons in culture. We report here increased phosphorylation of neurofilaments (NF) in the soma of chick spinal cord neurons in culture when exposed to CSF of ALS patients. Spinal cord neurons were cultured from 10-day embryonic chick and exposed to culture medium supplemented with CSF or serum (10%) from ALS and non-ALS patients for 48 h. There was a significant increase in the number of neuronal soma staining with antibodies against phosphorylated NF, following exposure to CSF from ALS patients. Such an increase, however, was not observed in cultures exposed to serum from ALS patients and also serum and CSF from non-ALS patients. These results suggest that the CSF of ALS patients may contain factor(s) which induces aberrant phosphorylation of NF in the soma, a probable forerunner to the formation of neurofibrillary tangles and eventual degeneration of neurons.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bigot D, Hunt SP (1991) The effects of quisqualate and nocodazole on the organization of MAP2 and neurofilaments in spinal cord neurons in vitro. Neurosci Lett 131: 21–26
Côle GM, Wu K, Tímiras PS (1985) A culture model for agerelated human neurofibrillary pathology. Int J Dev Neurosci 3: 23–32
Couratier P, Hugon J, Sindou P, Vallat JM, Dumas M (1993) Cell culture evidence for neuronal degeneration in amyotrophic lateral sclerosis being linked to glutamate AMPA/kainate receptors. Lancet 341: 265–268
Gajdusek DC (1987) Virus infection in aetiopathogenesis of motor neurone disease: a hypothesis for a final common path to neuronal lysis from multiple causes. In: Gourie-Devi M (ed) Motor neurone disease. Global clinical patterns and international research. Oxford and IBH, New Delhi, pp 83–92
Gourie-Devi M, Suresh TG, Shankar SK (1987) Pattern of motor neurone disease in South India and monomelic amyotrophy (A benign atypical form). In: Gourie-Devi M (ed) Motor neurone disease. Global clinical patterns and international research. Oxford and IBH, New Delhi, pp 171–190
Griffin JW, Clark AC, Parhad I, Watson DF, Hoffman PN (1991) The neuronal cytoskeleton in disorders of the motor neuron. Adv Neurol 56: 103–113
Hirano A (1991) Cytopathology of amyotrophic lateral sclerosis. Adv Neurol 56: 91–101
Hoffman PN, Lasek RJ (1975) The slow component of axonal transport. Identification of major structural polypeptides of the above and the generality among mammalian neurons. J Cell Biol 66: 351–356
Juurlink BHJ, Munoz DG, Devon RM (1991) Muscle derived motoneuron trophic factors promote the survival of motoneurons in vitro only when serum is present in the growth medium. Int J Neurosci 58: 249–254
Kurtzke JF (1982) Epidemiology of amyotrophic lateral sclerosis. Adv Neurol 36: 281–302
Leigh PN, Swash M (1991) Cytoskeletal pathology in motor neuron diseases. Adv Neurol 56: 115–124
Lichtenberg-Kraag B, Mandelkow EM, Biecna TJ, Steiner B, Schroter C, Gustke N, Meyer HE, Mandelkow E (1992) Phosphorylation-dependent epitopes of neurofilament antibodies on tau protein and relationship with Alzheimer tau. Proc Natl Acad Sci USA 89: 5384–5388
Manetto V, Sternberger NH, Perry G, Sternberger LA, Gambetti P (1988) Phosphorylation of neurofilaments is altered in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 47: 642–653
Mizusawa H, Matsumoto S, Yen SH (1989) Focal accumulation of phosphorylated neurofilaments within anterior horn cell in familial amyotrophic lateral sclerosis. Acta Neuropathol 79: 37–43
Raju TR, Meti BL (1993) Neuronal aging in vitro. An immunofluorescence study using chick embryo spinal cord cultures and antibodies against non-phosphorylated and phosphorylated neurofilaments. Natl Inst Mental Health Neurosci J 11: 49–54
Roisen Roisen FJ, Bartfeld H, Donnenfeld H, Benter J (1982) Neuron-specific in vitro cytoxicity of sera from patients with amyotrophic lateral sclerosis. Muscle Nerve 5: 48–53
Saitoh T, Masliah E, Jin L-W, Cole GM, Wieloch T, Shapiro IP (1991) Protein kinases and phosphorylation in neurologic disorders and cell death. Lab Invest 64: 596–616
Schulz M, Raju T, Ralstan G, Bennett MR (1990) A retinal ganglion cell neurotrophic factor purified from the superior colliculus. J Neurochem 55: 832–841
Taranath Shetty K, Link WJ, Pant SC (1993) Cdc2-like kinase from rat spinal cord specifically phosphorylate KSPXK motifs in neurofilament proteins: isolation and characterization. Proc Natl Acad Sci USA 90: 6844–6848
Wolfgram F, Myers L (1973) Amyotrophic lateral sclerosis: effect of serum on anterior horn cells in tissue culture. Science 179: 579–580
Author information
Authors and Affiliations
Additional information
Supported by a research grant from the National Institute of Mental Health and Neuro Sciences, Bangalore, India
Rights and permissions
About this article
Cite this article
Nagaraja, T.N., Raju, T.R., Gourie-Devi, M. et al. Neurofilament phosphorylation is enhanced in cultured chick spinal cord neurons exposed to cerebrospinal fluid from amyotrophic lateral sclerosis patients. Acta Neuropathol 88, 349–352 (1994). https://doi.org/10.1007/BF00310378
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00310378