| First Author | Vemula PK | Year | 2020 |
| Journal | Neurochem Int | Volume | 140 |
| Pages | 104798 | PubMed ID | 32711019 |
| Mgi Jnum | J:352661 | Mgi Id | MGI:7704293 |
| Doi | 10.1016/j.neuint.2020.104798 | Citation | Vemula PK, et al. (2020) Altered brain arginine metabolism with age in the APP(swe)/PSEN1(dE9) mouse model of Alzheimer's disease. Neurochem Int 140:104798 |
| abstractText | Amyloid-beta (Abeta) cleaved from amyloid precursor protein (APP) has been proposed to play a central and causative role in the aetiology of Alzheimer's disease (AD). APP(swe)/PSEN1(dE9) (APP/PS1) transgenic mice display chronic Abeta accumulation and deposition in the brain. L-arginine is a semi-essential amino acid with a number of bioactive metabolites, and altered arginine metabolism has been implicated in the pathogenesis and/or the development of AD. This study systematically investigated how arginine metabolic profiles changed in the frontal cortex, hippocampus, parahippocampal region and cerebellum of male APP/PS1 mice at 4, 9 and 17 months of age relative to their sex- and age-matched wildtype controls. Immunohistochemistry demonstrated age-related Abeta deposition in the brain. High-performance liquid chromatography and mass spectrometry revealed age-related increases in glutamine, spermidine and spermine in APP/PS1 mice in a region-specific manner. Notably, genotype-related increases in spermine were found in the frontal cortex at the 9-month age point and in the frontal cortex, hippocampus and parahippocampal region at 17 months of age. Given the existing literature indicating the role of polyamines (spermine in particular) in modulating the aggregation and toxicity of Abeta oligomers, increased spermidine and spermine levels in APP/PS1 mice may be a neuroprotective mechanism to combat Abeta toxicity. Future research is required to better understand the functional significance of these changes. |
