Objective To observe the effects of subchronic aluminum exposure on the expression of PTEN-induced kinase 1 (PINK1)/E3 ubiquitin ligase (Parkin) pathway microtubule-associated protein 1 light chain 3B (LC3B), selective autophagy receptor protein 62 (P62), and cytochrome c oxidase IV (COXIV) in rat hippocampal mitochondria, and to explore the specific mechanism by which aluminum exposure affects cognitive impairment through the mitophagy PINK1/Parkin pathway LC3B/P62/COXIV pathway.
Methods Thirty-two 6-week-old healthy male Sprague-Dawley (SD) rats of SPF grade, weighing (190±20) g, were randomly divided into four groups according to their body weight: control, low-dose (10 µmol/kg), medium-dose (20 µmol/kg), and high-dose (40 µmol/kg) groups, with 8 rats in each group. The animal intoxication model was established by intraperitoneal injection of aluminum maltolate for 90 days. After the exposure, the learning and memory abilities of the rats were measured by the Morris water maze behavioral test, the expression level of reactive oxygen species (ROS) in the cerebral cortex was measured by frozen sections, and the expression of PINK1, Parkin, LC3B, P62, and COXIV proteins in the hippocampal tissue was detected by Western blotting (WB).
Results On days 3, 4, and 5 of the Morris water maze place navigation test, the escape latency of rats in each group gradually increased with the increase of the exposure dose (P<0.05). On day 6, the number of times the rats in the high-dose group crossed the platform and the platform quadrant decreased compared with the control group and the low- and medium-dose groups (P<0.05). With the increase of the exposure dose in each group, the ROS level in the cerebral cortex of rats gradually increased (P<0.05), and the content of glutathione peroxidase (GSH-Px) gradually decreased (P<0.05). The relative expression levels of PINK1, Parkin, and LC3B in the hippocampal tissue of rats in each group gradually increased with the increase of the exposure dose (P<0.05), while the relative expression levels of P62 and COXIV gradually decreased with the increase of the exposure dose (P<0.05).
Conclusions Subchronic aluminum exposure can impair learning and memory function in rats, activate the PINK1/Parkin pathway LC3B/P62/COXIV pathway, and induce mitophagy.
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