【Introduction】Shati/Nat8l was discovered from drug addictive mice, which synthesizes N-acetyl aspartic acid (NAA), an important molecule for neuronal activity. We have been reported that Shati/Nat8l is involved in the cognitive function and stress sensitivity. Alzheimer’s disease (AD) is a dementia, one of whose characteristics is a deposition of senile plaques in the brain. Lower levels of NAA have been reported in the hippocampus of AD patients and AD model mice. Expression of Shati/Nat8l has also been reported to decrease in the AD model mice. However, involvement of Shati/Nat8l in AD pathogenesis has not been clarified. Here, we generated AD model mice with hippocampus-specific overexpression of Shati/Nat8l and determined the suppressive effects of Shati/Nat8l on AD pathogenesis.
【Methods】We selected 5xFAD transgenic line as AD model mice with senile plaque deposition. Shati/Nat8l was overexpressed by local injection of adeno-associated viral vector (AAV-Shati) into the hippocampus (AD-Shati). As a control group, AAV including GFP was injected to 5xFAD (AD-mock).
【Results】In a novel object recognition test, which evaluates cognitive function, cognitive impairment was confirmed in AD-mock mice as a typical phenotype of AD model mice. In comparison, cognitive function was improved in AD-Shati mice. There were no differences in the locomotor activity, anxiety-like behavior between AD-mock and AD-Shati.
【Discussion】Overexpression of Shati/Nat8l in the hippocampus ameliorated cognitive decline in a mouse model of AD.