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 MacColl Garfinkel, Jacob Raber

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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
Volume103
Issue number3
DOIs
StatePublished - Jan 2013

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Thioctic Acid
Irradiation
Nutrition
Data storage equipment
Diet
Cranial Irradiation
Brain
Radiation
Cognition
Microtubule-Associated Proteins
Confocal microscopy
Object recognition
Testing
Heat-Shock Proteins
Reversal Learning
Spatial Memory
Reactive Oxygen Species
Parahippocampal Gyrus
Antioxidants
Dentate Gyrus

Keywords

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

ASJC Scopus subject areas

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

Cite this

Effects of alpha-lipoic acid on associative and spatial memory of sham-irradiated and 56Fe-irradiated C57BL/6J male mice. / Villasana, Laura; Rosenthal, Rosalind A.; Doctrow, Susan R.; Pfankuch, Timothy; Zuloaga, Damian G.; Garfinkel, Alexandra MacColl; Raber, Jacob.

In: Pharmacology Biochemistry and Behavior, Vol. 103, No. 3, 01.2013, p. 487-493.

Research output: Contribution to journalArticle

Villasana, Laura ; Rosenthal, Rosalind A. ; Doctrow, Susan R. ; Pfankuch, Timothy ; Zuloaga, Damian G. ; Garfinkel, Alexandra MacColl ; Raber, Jacob. / Effects of alpha-lipoic acid on associative and spatial memory of sham-irradiated and 56Fe-irradiated C57BL/6J male mice. In: Pharmacology Biochemistry and Behavior. 2013 ; Vol. 103, No. 3. pp. 487-493.
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