Effects of aluminum on expressions of fat mass and obesity-associated protein and brain-derived neurotrophic factor in rat brain and PC12 cells

Background Chemical modification of RNA is a recent hotspot in the field of epigenetics, but the specific mechanism of chemical modification of RNA in aluminum neurotoxicity has not been fully reported.

Objective To investigate the alterations of fat mass and obesity-associated protein (FTO), that demethylates N6-methyladenosine (m⁶A), and brain-derived neurotrophic factor (BDNF) in different brain regions of rats and rat adrenal pheochromocytoma differentiated cells (PC12 cells) following aluminum exposure.

Methods Animal experiment: Twenty-four healthy male SD rats were randomly divided into a control group (normal saline) and 10, 20, and 40 μmol·kg⁻¹ exposure groups according to body weight, with 6 rats in each group. Maltol aluminum Al(mal)₃ was injected intraperitoneally every other day for 3 months. Cell experiment: PC12 cells were divided into a control group and 100, 200, and 400 μmol·L⁻¹ exposure groups exposed to Al(mal)₃ for 24 h. After exposure, the learning and memory ability of rats was measured by water maze experiment, and the protein expression levels of FTO and BDNF in rat cortex (n=6) and hippocampus (n=6) samples as well as in PC12 cells (n=5) were determined by Western blotting.

Results The results of water maze test showed that the escape latency of the 40 μmol·kg⁻¹Al(mal)₃ group was higher than those of the control group, the 10 μmol·kg⁻¹Al(mal)₃ group, and the 20 μmol·kg⁻¹Al(mal)₃ group on day 3, 4, and 5 of training (P<0.05). The retention time of the target quadrant of the 40 μmol·kg⁻¹Al(mal)₃ group was also reduced compared with that of the control group (P<0.05), indicating that aluminum exposure damaged the learning and memory ability of the rats. The Western blotting results showed that in the cortex, compared with the control group, the protein expression levels of FTO and BDNF in the aluminum treated groups were decreased (P<0.05). In the hippocampus, compared with the control group, the protein expression levels of FTO and BDNF in the 20 μmol·kg⁻¹ and the 40 μmol·kg⁻¹Al(mal)₃ groups were decreased (P<0.05). In PC12 cells, compared with the control group, the protein expression levels of FTO and BDNF in the aluminum treated groups were decreased (P<0.05).

Conclusion Aluminum-induced learning and memory impairment is related to a simultaneous reduction of FTO and BDNF protein expressions, suggesting that m⁶A methylation may be involved.