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Featured ArticleResearch Articles, Development/Plasticity/Repair

Developmental Changes in Brain Cellular Membrane and Energy Metabolism: A Multi-occasion 31P Magnetic Resonance Spectroscopy Study

Yana Fandakova, Naftali Raz, Ulman Lindenberger, Dalal Khatib, Usha Rajan and Jeffrey A. Stanley
Journal of Neuroscience 23 July 2025, 45 (30) e2222242025; https://doi.org/10.1523/JNEUROSCI.2222-24.2025
Yana Fandakova
1Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin 14195, Germany
2Department of Psychology and Institute for Cognitive & Affective Neuroscience, University of Trier, Trier 54296, Germany
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  • ORCID record for Yana Fandakova
Naftali Raz
1Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin 14195, Germany
3Department of Psychology, Stony Brook University, Stony Brook, New York 11794-2500
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Ulman Lindenberger
1Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin 14195, Germany
4Max Planck UCL Centre for Computational Psychiatry and Ageing Research, Berlin 14195, Germany and London WC1B 5EH, United Kingdom
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Dalal Khatib
5Department of Psychiatry and Behavioral Neurosciences, Brain Imaging Research Division, Tolan Park Building, School of Medicine, Wayne State University, Detroit, Michigan 48201
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Usha Rajan
5Department of Psychiatry and Behavioral Neurosciences, Brain Imaging Research Division, Tolan Park Building, School of Medicine, Wayne State University, Detroit, Michigan 48201
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Jeffrey A. Stanley
5Department of Psychiatry and Behavioral Neurosciences, Brain Imaging Research Division, Tolan Park Building, School of Medicine, Wayne State University, Detroit, Michigan 48201
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Abstract

Structural neuroimaging studies of typical development reveal increases in gray matter volume during childhood, followed by shrinkage in adolescence and early adulthood. With neuropil constituting the bulk of gray matter, these developmental changes may reflect neuropil reorganization accompanied by alterations in cellular membranes, as well as changes in related energy demand. Phosphorus magnetic resonance spectroscopy (31P MRS) allows in vivo assessment of changes in the brain's high-energy phosphates—phosphocreatine (PCr), inorganic phosphate (Pi), and adenosine triphosphate (ATP)—as well as metabolites associated with synthesis and degradation of membrane phospholipids (MPLs)—phosphocholine (PC) and phosphoethanolamine (PE)—and their breakdown products, glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE). Forty-nine children and adolescents aged 6–14 years at baseline (37 boys, 12 girls) were assessed on up to three occasions ca. 12 months apart. MPL precursor levels decreased across all examined regions over time, including cortical and subcortical gray matter and two major white matter tracts. Breakdown products increased in the prefrontal cortex (PFC) in younger children but decreased in their older counterparts. While ATP and Pi decreased across most regions, PCr changes were heterochronic and regional: hippocampal increases were more pronounced in older children, whereas most of the remaining regions showed no change. Changes in MPL precursors were positively associated with change in PFC cortical thickness, suggesting that the expansion and contraction of neuropil are coupled with structural brain changes during childhood and adolescence. Thus, in vivo 31P MRS provides new insights into the neurobiological mechanisms of normal brain development.

  • brain development
  • children
  • gray matter
  • in vivo neurochemistry
  • longitudinal
  • metabolites

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The Journal of Neuroscience: 45 (30)
Journal of Neuroscience
Vol. 45, Issue 30
23 Jul 2025
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Developmental Changes in Brain Cellular Membrane and Energy Metabolism: A Multi-occasion 31P Magnetic Resonance Spectroscopy Study
Yana Fandakova, Naftali Raz, Ulman Lindenberger, Dalal Khatib, Usha Rajan, Jeffrey A. Stanley
Journal of Neuroscience 23 July 2025, 45 (30) e2222242025; DOI: 10.1523/JNEUROSCI.2222-24.2025

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Developmental Changes in Brain Cellular Membrane and Energy Metabolism: A Multi-occasion 31P Magnetic Resonance Spectroscopy Study
Yana Fandakova, Naftali Raz, Ulman Lindenberger, Dalal Khatib, Usha Rajan, Jeffrey A. Stanley
Journal of Neuroscience 23 July 2025, 45 (30) e2222242025; DOI: 10.1523/JNEUROSCI.2222-24.2025
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Keywords

  • brain development
  • children
  • gray matter
  • in vivo neurochemistry
  • longitudinal
  • metabolites

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