{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T07:14:37Z","timestamp":1760426077794,"version":"3.41.2"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T00:00:00Z","timestamp":1659657600000},"content-version":"vor","delay-in-days":32,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008731","name":"European Leukodystrophy Association","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008731","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"crossref","award":["R01 MH65420"],"award-info":[{"award-number":["R01 MH65420"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Pelizaeus\u2013Merzbacher disease is an X-linked recessive leucodystrophy of the central nervous system caused by mutations affecting the major myelin protein, proteolipid protein 1. The extent of the altered in vivo neurochemistry of protein, proteolipid protein 1 duplications, the most common form of Pelizaeus\u2013Merzbacher disease, is, however, poorly understood. Phosphorus magnetic resonance spectroscopy is the only in vivo technique that can assess the biochemistry associated with high-energy phosphate and membrane phospholipid metabolism across different cortical, subcortical and white matter areas. In this cross-sectional study, whole-brain, multi-voxel phosphorus magnetic resonance spectroscopy was acquired at 3\u2005T on 14 patients with Pelizaeus\u2013Merzbacher disease with protein, proteolipid protein 1 duplications and 23 healthy controls (all males). Anabolic and catabolic levels of membrane phospholipids (phosphocholine and phosphoethanolamine, and glycerophosphoethanolamine and glycerophosphocholine, respectively), as well as phosphocreatine, inorganic orthophosphate and adenosine triphosphate levels relative to the total phosphorus magnetic resonance spectroscopy signal from 12 different cortical and subcortical areas were compared between the two groups. Independent of brain area, phosphocholine, glycerophosphoethanolamine and inorganic orthophosphate levels were significantly lower (P\u2009=\u20090.0025, P\u2009&amp;lt;\u20090.0001 and P\u2009=\u20090.0002) and phosphocreatine levels were significantly higher (P\u2009&amp;lt;\u20090.0001) in Pelizaeus\u2013Merzbacher disease patients compared with controls. Additionally, there was a significant group-by-brain area interaction for phosphocreatine with post-hoc analyses demonstrating significantly higher phosphocreatine levels in patients with Pelizaeus\u2013Merzbacher disease compared with controls across multiple brain areas (anterior and posterior white matter, superior parietal lobe, posterior cingulate cortex, hippocampus, occipital cortex, striatum and thalamus; all P\u2009\u2264\u20090.0042). Phosphoethanolamine, glycerophosphoethanolamine and adenosine triphosphate levels were not significantly different between groups. For the first-time, widespread alterations in phosphorus magnetic resonance spectroscopy metabolite levels of Pelizaeus\u2013Merzbacher disease patients are being reported. Specifically, increased high-energy phosphate storage levels of phosphocreatine concomitant with decreased inorganic orthophosphate across multiple areas suggest a widespread reduction in the high-energy phosphate utilization in Pelizaeus\u2013Merzbacher disease, and the membrane phospholipid metabolite deficits suggest a widespread degradation in the neuropil content\/maintenance of patients with Pelizaeus\u2013Merzbacher disease which includes axons, dendrites and astrocytes within cortex and the myelin microstructure and oligodendrocytes within white matter. These results provide greater insight into the neuropathology of Pelizaeus\u2013Merzbacher disease both in terms of energy expenditure and membrane phospholipid metabolites. Future longitudinal studies are warranted to investigate the utility of phosphorus magnetic resonance spectroscopy as surrogate biomarkers in monitoring treatment intervention for Pelizaeus\u2013Merzbacher disease.<\/jats:p>","DOI":"10.1093\/braincomms\/fcac202","type":"journal-article","created":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T17:59:42Z","timestamp":1659722382000},"source":"Crossref","is-referenced-by-count":2,"title":["Altered high-energy phosphate and membrane metabolism in Pelizaeus\u2013Merzbacher disease using phosphorus magnetic resonance spectroscopy"],"prefix":"10.1093","volume":"4","author":[{"given":"Jeremy J","family":"Laukka","sequence":"first","affiliation":[{"name":"Department of Medical Education, University of Toledo College of Medicine and Life Sciences , Toledo, OH , USA"},{"name":"Department of Neurology, University of Toledo College of Medicine and Life Sciences , Toledo, OH , 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