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Cerebrospinal fluid ATP metabolites in multiple sclerosis

Cerebrospinal fluid ATP metabolites in multiple sclerosis
Cerebrospinal fluid ATP metabolites in multiple sclerosis
Increased axonal energy demand and mitochondrial failure have been suggested as possible causes for axonal degeneration and disability in multiple sclerosis.

Our objective was to test whether ATP depletion precedes clinical, imaging and biomarker evidence for axonal degeneration in multiple sclerosis.

The method consisted of a longitudinal study which included 21 patients with multiple sclerosis. High performance liquid chromatography was used to quantify biomarkers of the ATP metabolism (oxypurines and purines) from the cerebrospinal fluid at baseline. The Expanded Disability Status Scale, MRI brain imaging measures for brain atrophy (ventricular and parenchymal fractions), and cerebrospinal fluid biomarkers for axonal damage (phosphorylated and hyperphosphorylated neurofilaments) were quantified at baseline and 3-year follow-up.

Central ATP depletion (sum of ATP metabolites >19.7 µmol/litre) was followed by more severe progression of disability if compared to normal ATP metabolites (median 1.5 versus 0, p < 0.05). Baseline ATP metabolite levels correlated with change of Expanded Disability Status Scale in the pooled cohort (r = 0.66, p = 0.001) and subgroups (relapsing–remitting patients: r = 0.79, p < 0.05 and secondary progressive/primary progressive patients: r = 0.69, p < 0.01). There was no relationship between central ATP metabolites and either biomarker or MRI evidence for axonal degeneration.

The data suggests that an increased energy demand in multiple sclerosis may cause a quantifiable degree of central ATP depletion. We speculate that the observed clinical disability may be related to depolarisation associated conduction block.
energy metabolism, atp, multiple sclerosis, mitochondria
1352-4585
549-554
Lazzarino, G.
bae2ec3b-fa81-4f36-a968-8a2e5f4e3d09
Amorini, A.M.
b4aa1124-07a8-4106-9d80-d7509101b559
Eikelenboom, M.J.
a4832207-2e8f-49df-8a1d-8912cc6065cc
Killestein, J.
38d15b28-dcf9-4b36-858d-000a5a2d94c6
Belli, A.
173116e3-a9e8-4ed2-afc4-932f7001eeb0
Di Pietro, V.
1ebabbfd-3a8f-4507-8e76-b58fac0673aa
Tavazzi, B.
ae8a9acc-cc89-4a7a-b846-21125e9624b1
Barkhof, F.
88b1f87e-5e81-4080-ad9b-f2b0c57d2ecb
Polman, C.H.
1b8a6da4-2a0a-4015-b31c-5ee45be8c8d8
Uitdehaag, B.M.J.
230b02b6-c43b-40ef-a60d-245f0b32e501
Petzold, A.
3142ddf4-b2e1-4f9f-bfad-ba869e3b190f
University of Catania
Lazzarino, G.
bae2ec3b-fa81-4f36-a968-8a2e5f4e3d09
Amorini, A.M.
b4aa1124-07a8-4106-9d80-d7509101b559
Eikelenboom, M.J.
a4832207-2e8f-49df-8a1d-8912cc6065cc
Killestein, J.
38d15b28-dcf9-4b36-858d-000a5a2d94c6
Belli, A.
173116e3-a9e8-4ed2-afc4-932f7001eeb0
Di Pietro, V.
1ebabbfd-3a8f-4507-8e76-b58fac0673aa
Tavazzi, B.
ae8a9acc-cc89-4a7a-b846-21125e9624b1
Barkhof, F.
88b1f87e-5e81-4080-ad9b-f2b0c57d2ecb
Polman, C.H.
1b8a6da4-2a0a-4015-b31c-5ee45be8c8d8
Uitdehaag, B.M.J.
230b02b6-c43b-40ef-a60d-245f0b32e501
Petzold, A.
3142ddf4-b2e1-4f9f-bfad-ba869e3b190f

Lazzarino, G., Amorini, A.M., Eikelenboom, M.J., Killestein, J., Belli, A., Di Pietro, V., Tavazzi, B., Barkhof, F., Polman, C.H., Uitdehaag, B.M.J. and Petzold, A. , University of Catania (2010) Cerebrospinal fluid ATP metabolites in multiple sclerosis. Multiple Sclerosis Journal, 16 (5), 549-554. (doi:10.1177/1352458510364196). (PMID:20194579)

Record type: Article

Abstract

Increased axonal energy demand and mitochondrial failure have been suggested as possible causes for axonal degeneration and disability in multiple sclerosis.

Our objective was to test whether ATP depletion precedes clinical, imaging and biomarker evidence for axonal degeneration in multiple sclerosis.

The method consisted of a longitudinal study which included 21 patients with multiple sclerosis. High performance liquid chromatography was used to quantify biomarkers of the ATP metabolism (oxypurines and purines) from the cerebrospinal fluid at baseline. The Expanded Disability Status Scale, MRI brain imaging measures for brain atrophy (ventricular and parenchymal fractions), and cerebrospinal fluid biomarkers for axonal damage (phosphorylated and hyperphosphorylated neurofilaments) were quantified at baseline and 3-year follow-up.

Central ATP depletion (sum of ATP metabolites >19.7 µmol/litre) was followed by more severe progression of disability if compared to normal ATP metabolites (median 1.5 versus 0, p < 0.05). Baseline ATP metabolite levels correlated with change of Expanded Disability Status Scale in the pooled cohort (r = 0.66, p = 0.001) and subgroups (relapsing–remitting patients: r = 0.79, p < 0.05 and secondary progressive/primary progressive patients: r = 0.69, p < 0.01). There was no relationship between central ATP metabolites and either biomarker or MRI evidence for axonal degeneration.

The data suggests that an increased energy demand in multiple sclerosis may cause a quantifiable degree of central ATP depletion. We speculate that the observed clinical disability may be related to depolarisation associated conduction block.

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More information

Published date: 1 March 2010
Keywords: energy metabolism, atp, multiple sclerosis, mitochondria

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Local EPrints ID: 73623
URI: http://eprints.soton.ac.uk/id/eprint/73623
ISSN: 1352-4585
PURE UUID: cb1fdcda-8bee-4d61-9b7c-577c6ea6576f

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Date deposited: 10 Mar 2010
Last modified: 13 Mar 2024 22:12

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Contributors

Author: G. Lazzarino
Author: A.M. Amorini
Author: M.J. Eikelenboom
Author: J. Killestein
Author: A. Belli
Author: V. Di Pietro
Author: B. Tavazzi
Author: F. Barkhof
Author: C.H. Polman
Author: B.M.J. Uitdehaag
Author: A. Petzold
Corporate Author: University of Catania

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