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

Abstract

The present study represents the first longitudinal, within-subject 1H 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 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 change 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 concentrations of N-acetylaspartate + N-acetylaspartylglutamate, glutamate + glutamine, and glycerophosphocholine + phosphocholine observed between postnatal days 35 and 60. 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.

Effect of diet on brain metabolites and behavior in spontaneously hypertensive rats

“…Although based on the work from Morgan and colleagues [69], the time frame in our study may be sufficient to reflect brain metabolite changes; however, others [70] have shown that in animals born with depletion in omega 3 fatty acids, the effects could possibly be reversed with supplemental diet when the supplementation was given from birth, but when the diet was given starting at weaning, recovery was only partial [70]. The onset of feeding (at weaning) and the duration of the diet (almost 6 weeks) may account for the lack of significant behavioral differences.…”

Characterization of the response of taurine protons to PRESS at 9.4 T for Resolving choline and Determining taurine T2

“…The imaging sequence employed a TE of 13 ms and a TR of 1250 ms. Fifteen transverse slices and seven coronal slices (thickness, 2 mm) were obtained of the rat brain. A 5 × 5 × 5-mm 3 voxel was approximately centered in the brain, with its center a distance of approximately 6 mm from the surface. Effort was made to ensure that the voxel was located in a similar location in each rat, but no segmentation procedures were carried out.…”

“…Proton magnetic resonance spectroscopy ( 1 H MRS) studies of mouse and rat brain at high magnetic field strengths, such as 9.4 T, have been demonstrated to be useful for the study of a variety of animal models of disease 1 and of brain developmental changes. 2,3 Taurine (Tau) is a relevant brain metabolite in the study of brain tumors, the brain and its development. [4][5][6][7][8] At 9.4 T, the Tau resonance at 3.42 ppm is sufficiently well resolved from other metabolite peaks to be utilized for quantification.…”

“…The levels of Cho have been shown to be altered in MRS examinations investigating brain tumors, 14 hypomyelination 15 and postnatal mouse brain development. 16 The Cho peak in rat and mouse brain has been shown to contain significant signal contamination from the Tau resonance at about 3.25 ppm, even at a high field strength of 9.4 T. 17,18 The quantification of Cho has been performed by either relying on spectral fitting software, such as LCModel, 2,3 or by subtracting the area of the other Tau resonance at approximately 3.42 ppm from the combined Cho and Tau peak. 16,19 The latter method may suffer from subtraction errors and uncertainties from making the assumption that the two Tau resonances are identical in the experimentally acquired spectrum.…”

Evaluating long-term consequences of adolescent antipsychotic exposure

“…A recent longitudinal magnetic resonance imaging (MRI) study in rats has also identified a peak in cortical thickness during adolescence and a continued increase in volume of cerebral cortex and striatum and myelination from adolescence to adulthood (until PND60) (Mengler et al 2014). Levels of striatal metabolites such as N-acetylaspartate (NAA), glutamate and glutamine have also been observed to increase from neonatal period through adolescence to adulthood as examined in a longitudinal magnetic resonance spectroscopy (MRS) study in rats (Morgan et al 2013). Detailed reviews on maturation of adolescent neuronal systems can be found elsewhere (Brenhouse and Andersen 2011;Lewis 1997;McCutcheon and Marinelli 2009;Spear 2000;Sturman and Moghaddam 2011;Wahlstrom et al 2010).…”