Neurochemical profile of the mouse hypothalamus using in vivo¹H MRS at 14.1T

Abstract

The hypothalamus plays an essential role in the central nervous system of mammals by among others regulating glucose homeostasis, food intake, temperature, and to some extent blood pressure. Assessments of hypothalamic metabolism using, e.g. 1 H MRS in mouse models can provide important insights into its function. To date, direct in vivo 1 H MRS measurements of hypothalamus have not been reported. Here, we report that in vivo single voxel measurements of mouse hypothalamus are feasible using 1 H MRS at 14.1T. Localized 1 H MR spectra from hypothalamus were obtained unilaterally (2-2.2 mL, VOI) and bilaterally (4-4.4 mL) with a quality comparable to that of hippocampus (3-3.5 mL). Using LCModel, a neurochemical profile consisting of 21 metabolites was quantified for both hypothalamus and hippocampus with most of the Cramé r-Rao lower bounds within 20%. Relative to the hippocampus, the hypothalamus was characterized by high g-aminobutryric acid and myo-inositol, and low taurine concentrations. When studying transgenic mice with no glucose transporter isoform 8 expressed, small metabolic changes were observed, yet glucose homeostasis was well maintained. We conclude that a specific neurochemical profile of mouse hypothalamus can be measured by 1 H MRS which will allow identifying and following metabolic alterations longitudinally in the hypothalamus of genetic modified models.

In Vivo Longitudinal 1H MRS Study of Transgenic Mouse Models of Prion Disease in the Hippocampus and Cerebellum at 14.1 T

“…In our study, the high quality of mouse brain spectra was achieved due to shimming with FASTMAP and also due to high signal intensity provided by the spinecho full intensity localization technique (SPECIAL) in a scan time of 25 min. The water linewidths were comparable with previously published mouse data [24,25], with slightly larger water linewidths in the cerebellum compared to hippocampus. This is mainly due to the fact that the cerebellum has higher microscopic heterogeneity but also due to its location (closer to the neck with a potentially higher risk of movement).…”

Glutamatergic and GABAergic TCA Cycle and Neurotransmitter Cycling Fluxes in Different Regions of Mouse Brain

“…The observed patterns of variation in the level of neurometabolite across the brain were found to be in agreement with the previous in vivo studies in mice. [24][25][26] Glu and NAA levels were found to be highest in the cortical region, indicating more excitatory synapses and density of neurons in the cerebral cortex. The finding of higher level of Glu in the cortical region is consistent with earlier reports, which stated that the excitatory synapses outnumber the inhibitory synapses in the cerebral cortex.…”

Effect of Manganese Chloride on the Neurochemical Profile of the Rat Hypothalamus

“…However, GABA and myo-Ins concentrations were also lower relative to the rat hippocampus, whereas these metabolites had significantly higher levels in the mouse hypothalamus relative to the hippocampus (Lei et al, 2010). g-Aminobutyric acid is known to have an important inhibitory role in the regulation of the hypothalamic-pituitary-adrenocortical axis (Cullinan et al, 2008) and especially at the level of the paraventricular nucleus (Cullinan et al, 2008).…”