Lanthanum chloride reduces lactate production in primary culture rat cortical astrocytes and suppresses primary co-culture rat cortical astrocyte-neuron lactate transport
- 310 Downloads
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.
KeywordsLanthanum Lactate production Astrocyte-neuron lactate transport Long-term memory
Astrocyte-neuron lactate transport
Glucose transporter 1
This work was supported by the National Nature Science Foundation of China (nos. 81273117 and 81673220 and 81373024). All experiments were conducted in compliance with the APPIVE guidelines.
Compliance with ethical standards
Conflict of interest
The authors declare that there are no conflicts of interest.
- Chen Z (2004) The hormesis effect of rare earths and potential impact of application in agriculture on the agriculture environment. Rural Ecol Environ 20:1–5 (in Chinese) Google Scholar
- Chen Z (2005) Brain accumulation, toxicity and potential hazards to human health in rare earths. Rural Ecol Environ 72:73–80 (in Chinese) Google Scholar
- Choeiri C, Staines W, Miki T, Seino S, Messier C (2005) Glucose transporter plasticity during memory processing. Neuroscience 130:591–600. https://doi.org/10.1016/j.neuroscience.2004.09.011 CrossRefPubMedGoogle Scholar
- Fan G, Yuan Z, Zheng H, Liu Z (2004) Study on the effects of exposure to rare earth elements and health-responses in children aged 7–10 years. Wei sheng yan jiu = J Hyg Res 33:23–28Google Scholar
- Gibbs ME, O’Dowd BS, Hertz E, Hertz L (2006) Astrocytic energy metabolism consolidates memory in young chicks. Neuroscience 141:9–13. https://doi.org/10.1016/j.neuroscience.2006.04.038 CrossRefPubMedGoogle Scholar
- Jakoby P, Schmidt E, Ruminot I, Gutierrez R, Barros LF, Deitmer JW (2014) Higher transport and metabolism of glucose in astrocytes compared with neurons: a multiphoton study of hippocampal and cerebellar tissue slices. Cereb Cortex 24:222–231. https://doi.org/10.1093/cercor/bhs309 CrossRefPubMedGoogle Scholar
- Jin M, Huang Y, Hu Y, Qiao M, Wang X (2014) Rare earth elements content and health risk assessment of soil and crops in typical rare earth mine area in Jiangxi Province. Acta Sci Circumst 34:3084–3093Google Scholar
- Libao R, Xiaoyan W, Qing X, Jingxiu L, Zhuo H, Ying D, Jingyu W (2007) Study on the correlation of light rare earth elements content in rat brain tissue. Chin J Anal Lab. https://doi.org/10.13595/j.cnki.issn1000-0720.2007.0214 Google Scholar
- Rutten K, Prickaerts J, Hendrix M, van der Staay FJ, Sik A, Blokland A (2007b) Time-dependent involvement of cAMP and cGMP in consolidation of object memory: studies using selective phosphodiesterase type 2, 4 and 5 inhibitors. Eur J Pharmacol 558:107–112. https://doi.org/10.1016/j.ejphar.2006.11.041 CrossRefPubMedGoogle Scholar
- Tadi M, Allaman I, Lengacher S, Grenningloh G, Magistretti PJ (2015) Learning-induced gene expression in the hippocampus reveals a role of neuron -astrocyte metabolic coupling in long term memory. PloS One 10:e0141568. https://doi.org/10.1371/journal.pone.0141568 CrossRefPubMedPubMedCentralGoogle Scholar
- Xiaofei L, Zhibiao C, yonghe Z, Zhiqiang C (2013) Evaluation of rare earth elements content and health risk of soil and vegetables in rare earth mining area. J Environ Sci:835–843Google Scholar
- Zhang XJ, Li TY, Liu YX, Chen J, Qu P, Wei XP, He J (2010) Primary culture of rat hippocampal neurons and detection of the neuronal excitability. Nan fang yi ke da xue xue bao = J South Med Univ 30:2080–2083Google Scholar
- Zhao Y, Yang J, QufangLiu, Jin C, Wu S, Wang C, Cai Y (2013) Effects of lanthanum on the spatial learning, memory,c AMP content and PKA expression in the hippocampus of rats. J Toxicol:321–324Google Scholar