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Cerium (Ce) compounds are now widely applied in medicine, agriculture, animal breeding, and daily life; however, the effects of Ce on human body, especially on the central nervous system, are still unclear. In order to investigate whether Ce exposure cause neurotoxicological effects, ICR mice were exposed to CeCl(3) through intragastric administration at 0, 2, 10, and 20 mg/kg body weight doses everyday for 60 days. The behaviors of spatial recognition memory, brain histopathology, the brain elements and neurochemicals, as well as enzymes activities in mice were determined. The Y-maze test showed that CeCl(3) exposure could significantly impair the behaviors of spatial recognition memory. Specifically, in these Ln(3+)-treated mice, the contents of Ca, Mg, Na, K, Fe, and Zn in brain were significantly altered, the activities of Na(+)/K(+)-ATPase, Ca(2+)-ATPase, Ca(2+)/Mg(2+)-ATPase, acetylcholine esterase, and nitric oxide synthase were significantly inhibited; monoamines neurotransmitters such as norepinephrine, dopamine, and 5-hydroxytryptamine were significantly decreased, while the contents of acetylcholine, glutamate, and nitric oxide were significantly increased. These results indicated that CeCl(3) exposure could impair the learning ability, which is attributed to the disturbance of the homeostasis of trace elements, enzymes, and neurotransmitter systems in the mouse brain. Therefore, our study aroused the attention of Ln application and long-term exposure effects.