Lithium prevents acrolein-induced neurotoxicity in HT22 mouse hippocampal cells

Neurochem Res. 2014 Apr;39(4):677-84. doi: 10.1007/s11064-014-1252-z. Epub 2014 Feb 13.


Acrolein is a highly electrophilic alpha, beta-unsaturated aldehyde to which humans are exposed in many situations and has been implicated in neurodegenerative diseases, such as Alzheimer's disease. Lithium is demonstrated to have neuroprotective and neurotrophic effects in brain ischemia, trauma, neurodegenerative disorders, and psychiatric disorders. Previously we have found that acrolein induced neuronal death in HT22 mouse hippocampal cells. In this study, the effects of lithium on the acrolein-induced neurotoxicity in HT22 cells as well as its mechanism(s) were investigated. We found that lithium protected HT22 cells against acrolein-induced damage by the attenuation of reactive oxygen species and the enhancement of the glutathione level. Lithium also attenuated the mitochondrial dysfunction caused by acrolein. Furthermore, lithium significantly increased the level of phospho-glycogen synthase kinase-3 beta (GSK-3β), the non-activated GSK-3β. Taken together, our findings suggest that lithium is a protective agent for acrolein-related neurotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrolein / antagonists & inhibitors*
  • Acrolein / toxicity*
  • Animals
  • Cell Line
  • Dose-Response Relationship, Drug
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Lithium Chloride / pharmacology*
  • Mice
  • Neuroprotective Agents / pharmacology*
  • Reactive Oxygen Species / metabolism


  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Acrolein
  • Lithium Chloride