Journal
TALANTA
Volume 253, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.talanta.2022.124046
Keywords
Alzheimer?s disease; Mass spectrometry imaging; Metabolic pathway; Glutamine-glutamate; GABA cycle; Neuronal activity
Categories
Funding
- National Key Plan for Scientific Research and Development of China [2019YFA045603, 2020YFA0509304, 2021YFA0805300]
- Chinese Academy of Sciences [QYZDY-SSW-SMC012, XDB39000000]
- National Natural Sciences Foundation of China [82030034, 81100861, 21775143]
- Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology [2017FXCX003]
- Fundamental Research Funds for the Central Universities [YD2070002003]
- Foundation form National Synchrotron Radiation Laboratory
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This study used a modified mass spectrometry imaging technique to visualize the spatial distributions of metabolites in the whole brain slices from AD mice. The researchers found dysfunction in the glutamine-glutamate/ GABA cycle, which might contribute to abnormal neural activity. The untargeted mapping of metabolic dysregulations during pathological progression in the AD model could provide implications for the pathogenesis and treatment of AD.
There is growing evidence that metabolic dysregulation contributes to the pathogenesis of Alzheimer's disease (AD). It is however difficult to detect multiple metabolites simultaneously in the different areas of the entire AD brain. Our research used a modified mass spectrometry imaging technique based on desorption electrospray ionization to visualize the spatial distributions of more than 300 compounds, including 119 putative metabolite candidates, in the whole brain slices from AD mice. Through such imaging measurements, we had quantified the level changes of more than 70 metabolites in 12 brain regions of AD mice. We had also evaluated metabolic pathway alterations in AD mice of various ages. In AD mice, we found a dysfunctional glutamine-glutamate/ GABA cycle with deficient production and release of glutamate in glutamatergic neurons and aberrant in-crease of GABA. Disordered metabolism of excitatory glutamate and inhibitory GABA might contribute to the abnormal neural activity. The untargeted mapping of metabolic dysregulations during pathological progression in the AD model might provide implications for the pathogenesis and treatment of AD.
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