MRS studies using animal models of human diseases facilitate biomarker identification and drug development because they allow delineation of the pathological correlates of biomarkers and screening of potential drugs in preclinical trials. As such, these animal studies enhance human applications of MRS, however, the interpretation and translation of animal data to human applications need additional considerations. First, the PF-573228 concentration regional differences

and developmental changes in metabolite levels120 need to be taken into account when designing studies. Of note, the neurochemical profile of the rodent and human brain is very similar, with only few differences, Inhibitors,research,lifescience,medical such as very high taurine levels in the rodent brain (Figure 4). Second,

potential effects of anesthesia, which is necessary for animal scanning, need to be considered. General anesthesia was not found to affect steady-state levels of MRS detectable metabolites in Inhibitors,research,lifescience,medical the brain, except for glucose and lactate.121,122 Figure 4. Neurochemical profiles of human and mouse cerebellum. Concentrations ± SD (µmol/g) obtained from the cerebellum of 16 healthy volunteers (35±15 years old) and 6 mice (C57BL/6, 6-8 weeks old) at 4T and 9.4T, respectively. The concentrations Inhibitors,research,lifescience,medical … Diagnosis MRS can be utilized in preclinical and eventually clinical applications to distinguish, for example, transgenic mouse models from wild-type (WT) animals or patients from healthy controls. For the successful translation of biomarker data from animal models to humans,123 not only does the model need to faithfully reproduce the Inhibitors,research,lifescience,medical pathology and phenotype of the human disease, but the same biomarker alterations need to be observed in the mouse Inhibitors,research,lifescience,medical model and in patients. This is a critical consideration. MRS studies with various AD mouse models demonstrate this issue well. For example, among the different AD models studied with 1H MRS, APP-PS1 mice match the neurochemical profile found in human AD best.103 These mice

display reductions in NAA and glutamate, as well as an increase in myo-inositol. The myoinositol difference in particular had not been detected in other AD models, but is a prominent neurochemical alteration detected in human AD.110 A more recent studydemonstrated these neurochemical profile changes at an even earlier age than the APP-PS1 mice in a different AD Nature Reviews Molecular Cell Biology mouse model.124 In MPTP-intoxicated mice, well-accepted model of the dopaminergic denervation in Parkinson’s disease (PD), high field MRS enabled detection of elevated glutamate, glutamine and GABA levels in the striatum.125 Of these alterations, the GABA difference was confirmed in human PD at ultra-high field.126 Longitudinal changes in neurochemical profiles were also reported in transgenic117 and knock-in118,127 mouse models of Huntington’s disease (HD).