Accumulation and neuroprotective effects of lithium on hepatocellular carcinoma mice model

Nataliya Bgatova; Natalia Obanina; Iuliia Taskaeva; Viktoriia Makarova; Asel Rakhmetova; Svetlana Shatskaya; Nikita Khotskin; Evgenii Zavjalov

doi:10.1016/j.bbr.2023.114679

Accumulation and neuroprotective effects of lithium on hepatocellular carcinoma mice model

Behav Brain Res. 2024 Jan 5:456:114679. doi: 10.1016/j.bbr.2023.114679. Epub 2023 Sep 20.

Authors

Nataliya Bgatova¹, Natalia Obanina¹, Iuliia Taskaeva², Viktoriia Makarova¹, Asel Rakhmetova³, Svetlana Shatskaya⁴, Nikita Khotskin⁵, Evgenii Zavjalov⁵

Affiliations

¹ Research Institute of Clinical and Experimental Lymphology - Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.
² Research Institute of Clinical and Experimental Lymphology - Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia. Electronic address: taskaeva.iuliia@gmail.com.
³ Toraigyrov University, Pavlodar, Kazakhstan.
⁴ Institute of Solid State Chemistry and Mechanochemistry, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia.
⁵ Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia.

PMID: 37739227
DOI: 10.1016/j.bbr.2023.114679

Abstract

Aim: The peripheral tumor growth is accompanied by the accumulation of inflammatory mediators in the blood that can negatively influence blood-brain barrier function and neuronal structure and develop the cancer-associated depression. The aim of the study was to evaluate the neurobiological effects of lithium on hepatocellular carcinoma mice model.

Methods: In this study we analyzed the locomotor activity of lithium-treated tumor-bearing mice using the Phenomaster instrument. Inductively coupled plasma mass-spectral analysis was used to determine lithium levels in blood, brain, liver, kidneys, tumors and muscle tissues. The prefrontal cortex neurons ultrastructure was assessed by transmission electron microscopy. Expression of BDNF, GRP78, EEA1, LAMP1, and LC3 beta in neurons was determined by immunohistochemical analysis.

Results: A decrease in locomotor activity was found in animals with tumors. At the same time, the low expression levels of the neurotrophic factor BDNF and early endosomal marker EEA1 were revealed, as well as the decreased amount of synaptic vesicles and synapses was shown. Signs of endoplasmic reticulum stress and autophagy development in neurons of animals with tumors were noted. Lithium carbonate administration had a corrective effect on animal's behavior and the prefrontal cortex neurons structure.

Conclusions: In summary, lithium can restore the neuronal homeostasis in tumor-bearing mice.

Keywords: Autophagy; Endoplasmic reticulum stress; Lithium; Prefrontal cortex neurons; Tumor; Ultrastructure.