Lanthanum Chloride Impairs Learning and Memory and Induces Dendritic Spine Abnormality by Down-Regulating Rac1/PAK Signaling Pathway in Hippocampus of Offspring Rats

Lanthanum (La) is a natural rare earth element. It has neurotoxic effects which can impair learning and memory in humans. However, its mechanism of neurotoxicity is unclear. Learning and memory are coordinated by dendritic spines which form tiny protruding structures on the dendritic branches of neurons. This study investigated the effect of LaCl3 exposure to pregnant and lactating rats on the offspring rats’ learning and memory ability. In this study, rats were divided into 4 groups and given distilled water solution containing 0%, 0.125%, 0.25%, 0.5% LaCl3, respectively, and this was done from conception to the end of the location. The effects of LaCl3 on spatial learning and memory ability in offspring rats and in the development of dendritic spines in CA1 pyramidal cells were investigated. The results showed that LaCl3 impaired spatial learning and memory ability in offspring rats, and decreased dendritic spine density during development. In addition, LaCl3 can affect the expression of CaMKII, miRNA132, p250GAP, Tiam1, PARD3, and down-regulated the activation of Rac1 which led to a decrease in the expression of Rac1/PAK signaling pathway and downstream regulatory proteins Cortactin and actin-related protein 2/3 complex (Arp2/3 complex). This study indicated that the learning and memory impairment and the decrease of dendritic spine density in the offspring of LaCl3 exposure may be related to the down-regulation of the Rac1/PAK signaling pathway regulated by Tiam1 and p250GAP.