Altered brain arginine metabolism in a mouse model of tauopathy.
Tauopathies consist of intracellular accumulation of hyperphosphorylated and aggregated microtubule protein tau, which remains a histopathological feature of Alzheimer's disease (AD) and frontotemporal dementia. L-Arginine is a semi-essential amino acid with a number of bioactive molecules. Its downstream metabolites putrescine, spermidine, and spermine (polyamines) are critically involved in microtubule assembly and stabilization. Recent evidence implicates altered arginine metabolism in the pathogenesis of AD. Using high-performance liquid chromatographic and mass spectrometric assays, the present study systematically determined the tissue concentrations of L-arginine and its nine downstream metabolites in the frontal cortex, hippocampus, parahippocampal region, striatum, thalamus, and cerebellum in male PS19 mice-bearing human tau P301S mutation at 4, 8, and 12-14 months of age. As compared to their wild-type littermates, PS19 mice displayed early and/or prolonged increases in L-ornithine and altered polyamine levels with age. There were also genotype- and age-related changes in L-arginine, L-citrulline, glutamine, glutamate, and γ-aminobutyric acid in a region- and/or chemical-specific manner. The results demonstrate altered brain arginine metabolism in PS19 mice with the most striking changes in L-ornithine, polyamines, and glutamate, indicating a shift of L-arginine metabolism to favor the arginase-polyamine pathway. Given the role of polyamines in maintaining microtubule stability, the functional significance of these changes remains to be explored in future research.
['Vemula|Pranav|P|', 'Jing|Yu|Y|', 'Zhang|Hu|H|', 'Hunt|Jerry B|JB|', 'Sandusky-Beltran|Leslie A|LA|', 'Lee|Daniel C|DC|', 'Liu|Ping|P|']
D000818:Animals D001120:Arginine D001921:Brain D004195:Disease Models, Animal D006801:Humans D008297:Male D051379:Mice D008822:Mice, Transgenic D024801:Tauopathies D016875:tau Proteins
Arginine metabolism Tauopathy Polyamines Hippocampus L-Ornithine Glutamate