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Longitudinal 1H MRS of rat forebrain from infancy to adulthood reveals adolescence as a distinctive phase of neurometabolite development.

ABSTRACT: This study represents the first longitudinal, within-subject (1) H MRS investigation of the developing rat brain spanning infancy, adolescence and early adulthood. We obtained neurometabolite profiles from a voxel located in a central location of the forebrain, centered on the striatum, with smaller contributions for the cortex, thalamus and hypothalamus, on postnatal days 7, 35 and 60. Water-scaled metabolite signals were corrected for T1 effects and quantified using the automated processing software LCModel, yielding molal concentrations. Our findings indicate age-related concentration changes in N-acetylaspartate?+?N-acetylaspartylglutamate, myo-inositol, glutamate?+?glutamine, taurine, creatine?+?phosphocreatine and glycerophosphocholine?+?phosphocholine. Using a repeated measures design and analysis, we identified significant neurodevelopment changes across all three developmental ages and identified adolescence as a distinctive phase in normative neurometabolic brain development. Between postnatal days 35 and 60, changes were observed in the concentrations of N-acetylaspartate?+?N-acetylaspartylglutamate, glutamate?+?glutamine and glycerophosphocholine?+?phosphocholine. Our data replicate past studies of early neurometabolite development and, for the first time, link maturational profiles in the same subjects across infancy, adolescence and adulthood.

SUBMITTER: Morgan JJ

PROVIDER: S-EPMC3634877 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Longitudinal 1H MRS of rat forebrain from infancy to adulthood reveals adolescence as a distinctive phase of neurometabolite development.

Morgan Jonathan J JJ Kleven Gale A GA Tulbert Christina D CD Olson John J Horita David A DA Ronca April E AE

NMR in biomedicine 20130116 6

This study represents the first longitudinal, within-subject (1) H MRS investigation of the developing rat brain spanning infancy, adolescence and early adulthood. We obtained neurometabolite profiles from a voxel located in a central location of the forebrain, centered on the striatum, with smaller contributions for the cortex, thalamus and hypothalamus, on postnatal days 7, 35 and 60. Water-scaled metabolite signals were corrected for T1 effects and quantified using the automated processing so ...[more]

PMID: 23322706

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Project description:Selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs), and (es)ketamine are used to treat major depressive disorder (MDD). These different types of medication may involve common neural pathways related to glutamatergic and GABAergic neurotransmitter systems, both of which have been implicated in MDD pathology. We conducted a systematic review of pharmacological proton Magnetic Resonance Spectroscopy (1H-MRS) studies in healthy volunteers and individuals with MDD to explore the potential impact of these medications on glutamatergic and GABAergic systems. We searched PubMed, Web of Science and Embase and included randomized controlled trials or cohort studies, which assessed the effects of SSRIs, SNRIs, or (es)ketamine on glutamate, glutamine, Glx or GABA using single-voxel 1H-MRS or Magnetic Resonance Spectroscopic Imaging (MRSI). Additionally, studies were included when they used a field strength > 1.5 T, and when a comparison of metabolite levels between antidepressant treatment and placebo or baseline with post-medication metabolite levels was done. We excluded animal studies, duplicate publications, or articles with 1H-MRS data already described in another included article. Twenty-nine studies were included in this review. Fifteen studies investigated the effect of administration or treatment with SSRIs or SNRIs, and fourteen studies investigated the effect of (es)ketamine on glutamatergic and GABAergic metabolite levels. Studies on SSRIs and SNRIs were highly variable, generally underpowered, and yielded no consistent findings across brain regions or specific populations. Although studies on (es)ketamine were also highly variable, some demonstrated an increase in glutamate levels in the anterior cingulate cortex in a time-dependent manner after administration. Our findings highlight the need for standardized study and acquisition protocols. Additionally, measuring metabolites dynamically over time or combining 1H-MRS with whole brain functional imaging techniques could provide valuable insights into the effects of these medications on glutamate and GABAergic neurometabolism.

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Dataset Information

Longitudinal 1H MRS of rat forebrain from infancy to adulthood reveals adolescence as a distinctive phase of neurometabolite development.

Publications

Longitudinal 1H MRS of rat forebrain from infancy to adulthood reveals adolescence as a distinctive phase of neurometabolite development.

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