Neonatal aluminum hydroxide exposure induces social and cognitive dysfunction in adulthood mice

Abstract

Objective To investigate the effects of neonatal aluminum hydroxide [Al(OH)3] exposure in mice on social behavior and cognitive function in their adulthood. Methods Sixteen newborn C57BL/6 male mice of SPF class with body mass of 2~3 g were divided into 2 groups (n=8): the normal control group (C57+Sal) and the neonatal Al(OH)3 treated group [C57+ Al(OH)3]. Al(OH)3 was administered by intramuscular injection at doses of 290, 75, 100, 110 and 50 μg/kg on postnatal days of 3, 5, 7, 10 and 12, respectively. The control group received intramuscular injections of equal volumes of saline. The open field test, light-dark box test, elevated plus maze test were used to evaluate the motor function and anxiety-like behavior of mice; The grooming test and marble burying test were used to assess the repetitive stereotypic behavior of mice; The three-chamber social test was used to evaluate the social ability of mice; The novel object recognition, Y-maze and nest building test were used to evaluate the short-term memory function and cognitive function of mice; The Morris water maze test was used to evaluate the spatial memory ability and learning ability of mice. Sox2, GFAP, PCNA immunofluorescence assay was used to detect the number of neural stem cells and proliferating cells in the hippocampus; NeuN, S100β, Iba1 immunofluorescence assay was used to detect the differentiation of neurons, astrocytes and microglia in the hippocampus. Results Compared with the C57+Sal group, the C57+ Al(OH)3 group showed no significant changes in total distance, total center time and segmental distance in the open field test, as well as no significant changes in open arm time percentage in the elevated plus maze test and the percentage of dark box time in the light-dark box test. In the three-box socialization test, the C57+ Al(OH)3 group showed no difference in chamber time, a preference for unfamiliar objects in both chamber preference index and sniffing preference index (P < 0.05), and significantly higher grooming time than the control group (P < 0.05); The results of novel object recognition test and Y-maze test showed the C57+Al(OH)3 group had a significantly lower novel object recognition index and spontaneous alternation exploration behavior ratio than those in the control group (P < 0.05); In the morris water maze test, the C57+Al(OH)3 group had a significantly lower target quadrant time than those in the control group (P < 0.05). Compared with the C57+Sal group, the C57+Al(OH)3 group had a significantly reduced number of neural stem cells in the hippocampal dentate gyrus (P < 0.05), thinner granule layer thickness (P < 0.01) and increased differentiation of mature astrocytes (P < 0.05). Conclusion Neonatal Al(OH)3 exposure can lead to social and cognitive dysfunction in adult mice, which may be related to hippocampal developmental defects.

Keywords

• aluminum hydroxide
• social communication disorder
• cognitive function
• hippocampus
• neurotoxicity