Protective effect of glutamic-oxaloacetic transaminase on hippocampal neurons in Alzheimer's disease using model mice

Elsevier, Neuroscience Letters, Volume 803, 23 April 2023
Authors: 
Li H., Zhang D., Wang X., Wang S., Xiao M.

Alzheimer's disease (AD), a neurodegenerative disease affecting the elderly, frequently causes cognitive impairment and memory decline, and there are currently no effective therapeutic drugs available. Glutamate excitotoxicity is one of the pathogeneses of AD, and there is evidence that glutamic-oxaloacetic transaminase (GOT) can significantly reduce glutamate concentrations in the hippocampi of mice, but its role in APP/PS1 transgenic mice is unknown. We investigated the improvement of neurological function and related protein expression following subcutaneous injection of GOT in mice with AD. We performed immunohistochemical staining on the brain tissue of 3-, 6-, and 12-month-old mice and found that the content of the β-amyloid protein Aβ1-42 in the 6 months old GOT treatment group was significantly reduced. Meanwhile, the APP-GOT group outperformed the APP group in the water maze and spatial object recognition experiments. The number of neurons in the hippocampal CA1 area of the APP-GOT group increased when compared to the APP group according to Nissl staining. Electron microscopic examination of the hippocampal CA1 area demonstrated that the number of synapses in the APP-GOT group was more than that in the APP group, and the mitochondrial structure was relatively complete. Finally, the protein content of the hippocampus was detected. In comparison to the APP group, SIRT1 content increased in the APP-GOT group whereas Aβ1-42 content decreased, and Ex527 could reverse this trend. These results suggest that GOT can significantly improve the cognitive function of mice in the early stage of AD, and the underlying mechanism may be through decreasing Aβ1-42 and increasing SIRT1 expressions.