Neurochemical profile of the developing mouse cortex determined by in vivo¹H NMR spectroscopy at 14.1 T and the effect of recurrent anaesthesia

Abstract

The neurochemical profile of the cortex develops in a region and time specific manner, which can be distorted by psychiatric and other neurological pathologies. Pre-clinical studies often involve experimental mouse models. In this study, we determined the neurochemical profile of C57BL/6 mice in a longitudinal study design to provide a reference frame for the normal developing mouse cortex. Using in vivo proton NMR spectroscopy at 14 T, we measured the concentrations of 18 metabolites in the anterior and posterior cortex on postnatal days (P) 10, 20, 30, 60 and 90. Cortical development was marked by alterations of highly concentrated metabolites, such as N-acetylaspartate, glutamate, taurine and creatine. Regional specificity was represented by early variations in the concentration of glutamine, aspartate and choline. In adult animals, regional concentration differences were found for N-acetylaspartate, creatine and myo-inositol. In this study, animals were exposed to recurrent isoflurane anaesthesia. Additional experiments showed that the latter was devoid of major effects on behaviour or cortical neurochemical profile. In conclusion, the high sensitivity and reproducibility of the measurements achieved at 14 T allowed us to identify developmental variations of cortical areas within the mouse cortex.

Longitudinal neurochemical modifications in the aging mouse brain measured in vivo by 1H magnetic resonance spectroscopy

“…However, its concentration (signal) was found to change in certain pathologic conditions , during postnatal development (Kulak et al, 2010) and between gray and white matter (Mukherjee et al, 2000). Reduction of total creatine concentration with age was observed in the cortex, hippocampus, and striatum during aging (Fig.…”

“…Because in the brain choline is below the NMR detection limit and mainly GPC and PCho contribute to this intense resonance, the measured cholinecontaining compounds are likely reflecting membrane lipid synthesis rather than the biosynthesis of the neurotransmitter acetylcholine (reviewed in . During early development, brain choline increases with age in the mouse cortex (Kulak et al, 2010). The present study shows that this increase of tCho with age continued through adulthood and aging and that this increase was not specific to the cortex.…”

“…The neurochemical profiles of hippocampus, cortex, and striatum were determined longitudinally in 36 mice (19 males and 17 females) at the age of 3, 6, 12, 18, and 24 months. All scans were performed during the lightcycle under anesthesia of 1%e1.5% isoflurane in oxygen gas and the duration of each NMR scanning session was restricted to a maximum of 120 minutes (Kulak et al, 2010).…”

“…After desiccation, water content was calculated from the wet-dry weight difference. For younger animals, water content measurements were available from previous reports (Agrawal et al, 1968;Cohadon and Desbordes, 1986;Kulak et al, 2010;Larvaron et al, 2006).…”

“…At the age of 6 and 12 months, water content was 79 AE 1% (n ¼ 4) and 79 AE 1% (n ¼ 6), respectively, and reduced to 75 AE 1% at the age of 24 months (n ¼ 9, p < 0.01 vs. 6 and 12 months). Average reported water content at the age of 1 month was 80 AE 1% (Agrawal et al, 1968;Cohadon and Desbordes, 1986;Kulak et al, 2010;Larvaron et al, 2006). Water content at these ages and interpolated at the age of 3 and 18 months was used to estimate absolute concentration of metabolites in the brain.…”