Lithium chloride ameliorated spatial cognitive impairment through activating mTOR phosphorylation and inhibiting excessive autophagy in the repeated cerebral ischemia‑reperfusion mouse model

Abstract

Lithium has been previously demonstrated to alleviate cognitive impairment caused by neurodegenerative diseases and acute brain injuries; however, the specific mechanism remains elusive. In the present study, the C57BL/6 mouse model of spatial cognitive impairment induced by repeated cerebral ischemia-reperfusion was established. Morris water maze test was performed to evaluate the levels of spatial cognitive impairment. Nissl staining was used to observe any morphological alterations, whilst western blotting was performed to measure the expression levels of microtubule-associated protein light chain 3 (LC3) and Beclin1 in addition to mTOR phosphorylation. LiCl was found to significantly improve spatial learning and memory impairments according to data from the Morris water maze test. Nissl staining indicated that LiCl inhibited neuronal damage in the CA1 region of the hippocampus. Additionally, LiCl increased mTOR phosphorylation, reduced beclin1 expression and reduced the LC3 II/I expression ratio. Taken together, these findings suggest that LiCl may alleviate the spatial cognitive impairment induced by repeated cerebral ischemia-reperfusion. This observation may be attributed to the inhibition of excessive autophagy by LiCl through mTOR signaling activation.

Selenium attenuates ischemia/reperfusion injury‑induced damage to the blood‑brain barrier in hyperglycemia through PI3K/AKT/mTOR pathway‑mediated autophagy inhibition

“…The autophagic process can be activated by nutritional deprivation or other stressful conditions. Previous studies have revealed that autophagy is upregulated following cerebral I/R in diabetes ( 2 , 65 , 66 ). Autophagy is characterized by the formation of autophagosomes that can engulf cytosolic organelles.…”

Lithium and Stroke Recovery: A Systematic Review and Meta-Analysis of Stroke Models in Rodents and Human Data

“…10 Other studies have shown that lithium treatment is associated with antiapoptotic eff ects, 15,34,43,49,51,52 decreased expression of inflammatory markers, 31,42,43,45,50 reduced oxidative stress, 35,43,45 and activation of immunomediated responses involved in the restoration of blood-brain barrier integrity. 44,50 Finally, evidence of trophic responses is supported by the ability of lithium to upregulate the brain-derived neurotrophic factor production, 39,52,53 to promote neuronal differentiation, axonal plasticity, and endogenous neurogenesis, 14,28,42,45 as well as to stimulate poststroke angiogenesis. 53 According to the SYRCLE's tool, the overall assessment of the quality of animal studies included in the review was ranked as good, that is, low risk of bias in most domains; except for performance-and detection-blinding, where the risk of bias was observed in >50% of studies.…”

Lithium chloride promotes neural functional recovery after local cerebral ischaemia injury in rats through Wnt signalling pathway activation

“…Lithium chloride (LiCl, Sigma-Aldrich, USA) was dissolved in 0.9% NaCl, and both the M+L group and M+L+D group rats were then treated with LiCl twice a day at the dose of 2.0 mmol/kg for one consecutive week after MCAO operation according to formerly described [16]. The S group and M group rats simultaneously received equivalent volumes of normal saline injected.…”