To investigate the mechanism of IGF2/JAK2/STAT3 on learning and memory impairment induced by aluminum maltol in rats.

A total of 32 SD rats were divided into normal saline control group and low, medium and high maltol aluminum exposure groups (10, 20 and 40 μmol/kg) by random number table, respectively, and intraperitoneally injected every other day for three months. After exposure, Morris water maze was applied to examine the learning and memory ability of rats, and HE staining was used to check the arrangement of hippocampal neurons. Real-time fluorescence quantitative PCR was applied to detect the relative expression level of IGF2 mRNA in hippocampus of rats. Western Blotting was used for detecting the relative protein expression levels of Cleaved Caspase3, IGF2, p-JAK2(Tyr1007/1008), and p-STAT3(Ser727) in the hippocampus of rats.

With the increase of aluminum dose, the escape latency of rats in the same day was prolonged, and the residence time in the target quadrant and the times of crossing the platform were gradually reduced (F=7.900, P=0.001; F=6.693, P=0.002). HE staining results showed that the number of neurons in CA1 region of hippocampus gradually decreased and the arrangement of neurons was obviously loose with the increase of aluminum dose (F=25.947, P<0.001). With increasing aluminum dose, apoptosis-associated protein Bcl-2 levels decreased gradually (F=83.235, P<0.001), Bax (F=153.189, P<0.001) and Cleaved Caspase3 (F=11.636, P<0.01) levels was gradually increased, and the relative expression levels of IGF2 mRNA and IGF2, p-JAK2 (Tyr1007/1008), p-STAT3 (Ser727) proteins decreased gradually with the increase of aluminum dose (F=18.423, P<0.001; F=11.072, P=0.001; F=55.161, P<0.001; F=10.481, P=0.001).

Aluminum maltol can induce cell apoptosis by inhibiting IGF2/JAK2/STAT3 pathway, which could damage the learning and memory ability of rats.