Abstract
Ciliary neurotrophic factor (CNTF) rescues motor neurons in animal models of injury and neurodegeneration, and disruption of the mouse CNTF gene results in motor neuron degeneration in mature adults. Glial cells increase nerve growth factor (NGF) expression in neuropathological conditions, and the sensory system can be affected in the amyotrophic lateral sclerosis (ALS) type of motor neuronic disease. We therefore studied CNTF and NGF levels in post mortem spinal cord and cerebral cortex from patients with ALS and matched controls. We report a marked decrease of CNTF in the ventral horn of spinal cord in ALS, with no change in cerebral motor cortex. In contrast, NGF levels were decreased in ALS cerebral motor cortex, where the corticospinal tract originates, but increased in the lateral column of spinal cord, which includes the region of corticospinal tract degeneration in ALS. Both CNTF and NGF levels were decreased in ALS dorsal spinal cord.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Tandan, R., & Bradley, W.G Amyotrophic lateral sclerosis: Clinical features, pathology and ethical issues in management. Ann. Neurol. 18 271–280 (1985).
Hughes, J Pathology of amyotrophic lateral sclerosis. Adv. Neurol. 36 61–73 (1982).
Rosen, D.R. et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362 59–62 (1993).
Manthorpe, M., Louis, J.-C., Hagg, T. & Varon, S. Ciliary neu-ronotrophic factor. In: Neurotrophic Factors (eds Loughlin S.E. & Fallen J.H.) 443–474, (Academic Press, San Diego, 1993).
Ip, N.Y. et al. The alpha component of the CNTF receptor is required for signalling and defines potential CNTF targets in the adult and during development. Neuron 10 89–102 (1993).
Mitsumoto, H. et al. Arrest of motor neuron disease in wobbler mice cotreated with CNTF and BDNF. Science 265 1107–1110 (1994).
Sendtner, M., Kreutzberg, G.W., Thoenen, H. Ciliary neurotrophic factor prevents the degeneration of motor neurons after axotomy. Nature 345 440–441 (1990).
Oppenheim, R.W., Prevette, D., Qin-Wei, Y., Collins, F., & MacDonald, J. Control of embryonic motor neuron survival in vivo by ciliary neurotrophic factor. Science 251 1616–1618 (1991).
Sendtner, M. et al. neurotrophic factor prevents degeneration of motor neurons in mouse mutant progressive motor neuronopathy. Nature 358 502–504 (1992).
Mitsumoto, H. et al. The effects of ciliary neurotrophic factor on motor dysfunction in wobbler mouse motor neuron disease. Ann. Neurol 36 142–148 (1994).
Helgren, M.E. et al. Trophic effect of ciliary neurotrophic factor on den-ervated muscle. Cell 76 493–504 (1994).
Gurney, M.E., Yamamoto, H., & Kwon, Y. Induction of motor neuron sprouting in vivo by ciliary neurotrophic factor and basic fibroblast growth factor. J. Neurosci. 12 3241–3247 (1992).
Curtis, R. et al. Retrograde axonal transport of ciliary neurotrophic factor is increased by peripheral nerve injury. Nature 365 253–255 (1993).
Ip, N.Y., Wiegand, S.J., Morse, J., Rudge, J.S Injury-induced regulation of CNTF mRNA in the adult rat brain. Eur. J. Neurosci. 5 25–33 (1993).
Masu, Y. et al. Disruption of the CNTF gene results in motor neuron degeneration. Nature 365 27–32 (1993).
Takahashi, R. et al. A null mutation in the human CNTF gene is not causally related to neurological diseases. Nature Genet 7 79–84 (1994).
Dyck, P.J., Stevens, J.C., Mulder, D.W., & Espinosa, R.E. Frequency of nerve fibre degeneration of peripheral motor and sensory neurons in amyotrophic lateral sclerosis. Neurology 25 781–785 (1975).
Gregory, R., Mills, K., Donaghy, & M. Progressive sensory dysfunction in amyotrophic lateral sclerosis. J. Neurol. 240 309–314 (1993).
Fernandez, E. et al. Spinal cord transection in adult rats: Effect of local infusion of nerve growth factor on the corticospinal tract axons. Neuro-surgery 33 889–893 (1993).
Swash, M., Scholtz, C.L., Vowles, G., & Ingram, D. Selective and asymmetric vulnerability of corticospinal and spinocerebellar tracts in motor neuron disease. J. Neurol. Neurosurg. Psychiat. 51 785–789 (1988).
Davidson, C.D. Amyotrophic lateral sclerosis: Origin and extent of the upper motor neuron lesion. Arch. Neurol. 46 1039–1056 (1941).
Stockli, K.A. et al. Molecular cloning, expression and regional distribution of rat ciliary neurotrophic factor. Nature 342 920–923 (1989).
Rende, M. et al. Immunolocalisation of ciliary neuronotrophic factor in adult rat sciatic nerve. Glia 5 25–32 (1992).
Stockli, K.A. et al. Regional distribution, developmental changes, and cellular localisation of CNTF-mRNA and protein in the rat brain. Cell Biol. 115 447–459 (1991).
Friedmann, B. et al. Regulation of ciliary neurotrophic factor expression in myelin-related Schwann cells in vivo . Neuron 9 295–305 (1992).
Heumann, R., Korsching, S., Bandtlow, C., Thoenen, H. Changes of nerve growth factor synthesis in non-neuronal cells in response to sciatic nerve transection. J. Cell Biol. 104 1623–1631 (1987).
Bakhit, C., Armanini, M., Wong, W.L., Bennett, G.L., & Wrathall, J.R. Increase in nerve growth factor-like immunoreactivity and decrease in choline acetyltransferase following contusive spinal cord injury. Brain Res. 554 264–271 (1991).
Altar, C.A. et al. Recovery of cholinergic phenotype in the injured rat neostriatum: Role for endogenous and exogenous nerve growth factor. J. Neurochem. 59 2167–2177 (1992).
Lorez, H., Keller, F., Ruess, G., & Otten, U. Nerve growth factor increases in adult rat brain after hypoxic injury. Neurosci Lett. 98 339–344 (1989).
Magal, E., Louis, J.C., Oudega, M., & Varon, S. CNTF promotes the survival of neonatal rat corticospinal neurons in vitro . Neuroreport 4 779–782 (1993).
Anand, P. et al. A VIP containing system concentrated in the lum-bosacral region of human spinal cord. Nature 305 143–145 (1983).
Malessa, S., Leigh, P.N., Bertel, O., Sluga, E., & Hornykiewicz, O Amyotrophic lateral sclerosis: Glutamate dehydrogenase and transmitter amino acids in the spinal cord. J. Neurol. Neurosurg. Psychiat. 54 984–988 (1991).
Ikeda, K. et al. Effects of brain-derived neurotrophic factor on motor dysfunction in wobbler mouse motor neuron disease. Ann. Neurol, in the press.
Wong, V, Arriaga, R, Ip, N.Y., Lindsay, R.M. The neurotrophins BDNF, NT-3 and NT-4/5, but not NGF, up-regulate the cholinergic phenotype of developing motor neurons. Eur. J. Neurosci. 5 466–474 (1993).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Anand, P., Parrett, A., Martin, J. et al. Regional changes of ciliary neurotrophic factor and nerve growth factor levels in post mortem spinal cord and cerebral cortex from patients with motor disease. Nat Med 1, 168–172 (1995). https://doi.org/10.1038/nm0295-168
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/nm0295-168
This article is cited by
-
All-Trans Retinoic Acid Exerts Neuroprotective Effects in Amyotrophic Lateral Sclerosis-Like Tg (SOD1*G93A)1Gur Mice
Molecular Neurobiology (2020)
-
The potential roles of aquaporin 4 in amyotrophic lateral sclerosis
Neurological Sciences (2019)
-
Adipose-derived Stem Cell Conditioned Media Extends Survival time of a mouse model of Amyotrophic Lateral Sclerosis
Scientific Reports (2015)
-
Down regulation of trophic factors in neonatal rat spinal cord after administration of cerebrospinal fluid from sporadic amyotrophic lateral sclerosis patients
Journal of Neural Transmission (2011)
-
Amyotrophic lateral sclerosis
Orphanet Journal of Rare Diseases (2009)