Effects of alpha-lipoic acid on associative and spatial memory of sham-irradiated and 56Fe-irradiated C57BL/6J male mice

Laura Villasana, Rosalind A. Rosenthal, Susan R. Doctrow, Timothy Pfankuch, Damian G. Zuloaga, Alexandra Mac Coll Garfinkel, Jacob Raber

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Cranial irradiation with 56Fe, a form of space radiation, causes hippocampus-dependent cognitive changes. 56Fe irradiation also increases reactive oxygen species (ROS) levels, which may contribute to these changes. Therefore, we investigated the effects of the antioxidant alpha lipoic acid (ALA) on cognition following sham-irradiation and irradiation. Male mice were irradiated (brain only) with 56Fe (3 Gy) or sham-irradiated at 6-9 months of age. Half of the mice remained fed a regular chow and the other half of the mice were fed a caloric-matched diet containing ALA starting two-weeks prior to irradiation and throughout cognitive testing. Following cognitive testing, levels of 3-nitrotyrosine (3NT), a marker of oxidative protein stress, and levels of microtubule-associated protein (MAP-2), a dendritic protein important for cognition, were assessed using immunohistochemistry and confocal microscopy. ALA prevented radiation-induced impairments in spatial memory retention in the hippocampal and cortical dependent water maze probe trials following reversal learning. However, in sham-irradiated mice, ALA treatment impaired cortical-dependent novel object recognition and amygdala-dependent cued fear conditioning. There was a trend towards lower 3NT levels in irradiated mice receiving a diet containing ALA than irradiated mice receiving a regular diet. In the hippocampal dentate gyrus of mice on regular diet, irradiated mice had higher levels of MAP-2 immunoreactivity than sham-irradiated mice. Thus, ALA might have differential effects on the brain under normal physiological conditions and those involving environmental challenges such as cranial irradiation.

Original languageEnglish (US)
Pages (from-to)487-493
Number of pages7
JournalPharmacology Biochemistry and Behavior
Issue number3
StatePublished - Jan 2013


  • Alpha-lipoic acid
  • Antioxidants
  • Cognition
  • Fe irradiation
  • Fear conditioning
  • Object recognition
  • Radiation
  • Sex
  • Water maze
  • Wild-type mice

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience


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