文摘
Lanthanum chloride (LaCl3) can affect neurobehavioral development and impair cognitive abilities. The mechanism underlying LaCl3-induced neurotoxic effects is still unknown. The purpose of this research was to investigate the neuronal impairment induced by LaCl3 and discuss the possible mechanism from the aspects of the alteration of glutamate level, intracellular calcium concentration ([Ca2+]i), Bax, Bcl-2 and caspases expression in the hippocampus. Lactational rats were exposed to 0, 0.25, 0.50 and 1.0?% LaCl3 in drinking water, respectively. Their offspring were exposed to LaCl3 by parental lactation and then administrated with 0, 0.25, 0.50 and 1.0?% LaCl3 in drinking water for 1?month. The results showed that 0.25, 0.50 and 1.0?% LaCl3 exposure induced neuronal impairment in the hippocampus of young rat. Hippocampal glutamate level, [Ca2+]i and ratio of Bax and Bcl-2 expression increased significantly after LaCl3 exposure. Besides, LaCl3 exposure increased GRP78, GRP94, GADD153 and p-JNK expression, promoted the activation of caspase-3, caspase-9 and caspase-12, induced PARP cleavage and caused excessive apoptosis. These results indicate that LaCl3 increases glutamate level, [Ca2+]i and ratio of Bax and Bcl-2 expression, which cause excessive apoptosis by the mitochondrial and endoplasmic reticulum stress-induced pathway, and thus neuronal damages in the hippocampus.