Lanthanum chloride reduces lactate production in primary culture rat cortical astrocytes and suppresses primary co-culture rat cortical astrocyte-neuron lactate transport.

Author(s) Sun, Y.; Yang, J.; Hu, X.; Gao, X.; Li, Y.; Yu, M.; Liu, S.; Lu, X.; Jin, C.; Wu, S.; Cai, Y.
Journal Arch Toxicol
Date Published 2017 Dec 20
Abstract

Lanthanum (La) can impair learning memory and induce behavioral abnormalities in animals. However, the mechanism underlying these adverse effects of La is still elusive. It has been demonstrated that lactate derived from astrocytes is the major energy source for neurons during long-term memory (LTM) formation and the deficiency of lactate supply can result in LTM damage. However, little work has been done with respect to the impact of La on the lactate production in astrocytes and astrocyte-neuron lactate transport (ANLT). Herein, experiments were undertaken to explore if there was such an adverse effect of La. Primary culture rat cortical astrocytes and primary co-culture rat cortical astrocyte-neuron were treated with (0.125, 0.25 and 0.5 mM) lanthanum chloride (LaCl3) for 24 h. The results showed that LaCl3 treatment significantly downregulated the mRNA and protein expression of glucose transporter 1 (GLUT1), glycogen synthase (GS), glycogen phosphorylase (GP), lactate dehydrogenase A (LDHA), and monocarboxylate transporter 1, 2 and 4 (MCT 1 2 and 4); upregulated the mRNA and protein expression of lactate dehydrogenase B (LDHB); and decreased the glycogen level, total LDH and GP activity, GS/p-GS ratio and lactate contents. Moreover, rolipram (20, 40 μM) or forskolin (20, 40 μM) could increase the lactate content by upregulating GP expression and the GS/p-GS ratio, as well as antagonize the effects of La. These results suggested that La-induced learning-memory damage was probably related to its suppression of lactate production in astrocytes and ANLT. This study provides some novel clues for clarifying the mechanism underlying the neurotoxicity of La.

DOI 10.1007/s00204-017-2148-x
ISSN 1432-0738
Citation Sun Y, Yang J, Hu X, Gao X, Li Y, Yu M, et al. Lanthanum chloride reduces lactate production in primary culture rat cortical astrocytes and suppresses primary co-culture rat cortical astrocyte-neuron lactate transport. Arch Toxicol. 2017.

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