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

• Published in: Cellular and molecular neurobiology Vol. 40; no. 3; pp. 459 - 475
• Main Authors: Sun, Wenchang, Yang, Jinghua, Hong, Yunting, Yuan, Hui, Wang, Jianbo, Zhang, Yanqiang, Lu, Xiaobo, Jin, Cuihong, Wu, Shengwen, Cai, Yuan
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-04-2020; Springer Nature B.V
• Subjects: Actin; Actin-related protein 2; Animals; Animals, Newborn; Biomedical and Life Sciences; Biomedicine; Ca2+/calmodulin-dependent protein kinase II; Cell Biology; Dendritic spines; Dendritic Spines - drug effects; Dendritic Spines - metabolism; Dendritic Spines - pathology; Down-Regulation - drug effects; Female; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; Lactation - drug effects; Lactation - physiology; Lanthanum; Lanthanum - toxicity; Learning Disabilities - chemically induced; Learning Disabilities - physiopathology; Learning Disabilities - psychology; Male; Maternal Exposure - adverse effects; Maze Learning - drug effects; Memory - drug effects; Memory Disorders - chemically induced; Memory Disorders - physiopathology; Memory Disorders - psychology; Neurobiology; Neurosciences; Neurotoxicity; Neurotoxicity Syndromes - physiopathology; Neurotoxicity Syndromes - psychology; Offspring; Original Research; p21-Activated Kinases - metabolism; Pregnancy; Prenatal Exposure Delayed Effects - chemically induced; Prenatal Exposure Delayed Effects - physiopathology; Prenatal Exposure Delayed Effects - psychology; Pyramidal cells; rac1 GTP-Binding Protein - metabolism; Rac1 protein; Rats; Rats, Wistar; Regulatory proteins; Signal transduction; Signal Transduction - drug effects; Spatial discrimination learning; Spatial Learning - drug effects; Spatial memory; Tiam1 protein; Learning and memory; Dendritic spine; Lanthanum; Rac1; Hippocampus
• ISSN: 0272-4340; 1573-6830; 1573-6830
• DOI: 10.1007/s10571-019-00748-7

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 LaCl
3
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% LaCl
3
, respectively, and this was done from conception to the end of the location. The effects of LaCl
3
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 LaCl
3
impaired spatial learning and memory ability in offspring rats, and decreased dendritic spine density during development. In addition, LaCl
3
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 LaCl
3
exposure may be related to the down-regulation of the Rac1/PAK signaling pathway regulated by Tiam1 and p250GAP.