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Determination of polyamines in samples of human brain, spinal cord, CSF, muscle and muscle microdialysate by precolumn derivatization with 9-fluorenylmethyl chloroformate and high performance liquid chromatography
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
Article in journal (Refereed) Submitted
URN: urn:nbn:se:uu:diva-91274OAI: oai:DiVA.org:uu-91274DiVA: diva2:163953
Available from: 2004-01-22 Created: 2004-01-22Bibliographically approved
In thesis
1. Transmethylation, Polyamines and Apoptosis in Amyotrophic Lateral Sclerosis
Open this publication in new window or tab >>Transmethylation, Polyamines and Apoptosis in Amyotrophic Lateral Sclerosis
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive disorder characterized by degeneration of motor neurons in the cortex, brainstem and spinal cord. The patients usually die within 3-5 years after onset. The full etiology of ALS is unknown and many hypotheses have been proposed to explain the neurodegeneration. However, basic mechanisms of cellular function such as transmethylation and polyamine metabolism have not been extensively studied in ALS. Transmethylation reactions are very important in the synthesis of substrates such as proteins, neurotransmitters, DNA and RNA. The polyamines, putrescine, spermidine and spermine, are involved in essential functions such as cellular growth, proliferation and differentiation.

An initial study in this thesis concerned the process of neuronal death (apoptosis) in ALS spinal cord. The results showed increased levels of an apoptosis-stimulating protein and increased levels of DNA fragmentation indicative of an apoptotic process in the tissue. A comparative study of MAT-enzyme activity in spinal cord from different mammalian species was undertaken to provide a background for future studies on transmethylation and neurodegeneration. Transmethylation reactions were found altered in erythrocytes from males with ALS but not in spinal cord from ALS patients as compared to controls. An adaptation of previously described polyamine assays was made for the study of polyamines in ALS spinal cord. The method was validated and applied for polyamine analysis in human materials of different characteristics. Determination of polyamines in control and ALS spinal cords showed no major differences. However, in female ALS patients, significantly increased spermidine and spermine levels were observed in ventral horn regions. These gender-related alterations in transmethylation and polyamine metabolism are of interest since there is a male preponderance for the disease.

The lack of major differences in polyamine levels between ALS and control spinal cord suggests a maintained regulation of polyamines at the end stage of this neurodegenerative disease.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 62 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1319
Neurosciences, amyotrophic lateral sclerosis, neurodegeneration, transmethylation, polyamine, apoptosis, Neurovetenskap
National Category
urn:nbn:se:uu:diva-3952 (URN)91-554-5853-X (ISBN)
Public defence
2004-02-13, Hedstrandsalen, Akademiska Sjukhuset, Uppsala, 13:15
Available from: 2004-01-22 Created: 2004-01-22Bibliographically approved

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