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

ABSTRACT: Cranial irradiation with (56)Fe, a form of space radiation, causes hippocampus-dependent cognitive changes. (56)Fe 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 (56)Fe (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.

SUBMITTER: Villasana LE

PROVIDER: S-EPMC5930007 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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

Villasana Laura E LE Rosenthal Rosalind A RA Doctrow Susan R SR Pfankuch Timothy T Zuloaga Damian G DG Garfinkel Alexandra Maccoll AM Raber Jacob J

Pharmacology, biochemistry, and behavior 20121007 3

Cranial irradiation with (56)Fe, a form of space radiation, causes hippocampus-dependent cognitive changes. (56)Fe 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 (56)Fe (3 Gy) or sham-irradiated at 6-9 months of age. Half of the mice remained fed a regular cho ...[more]

PMID: 23051895

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Project description:The lifelong relationship between microorganisms and hosts has a profound impact on the overall health and physiology of the holobiont. Microbiome composition throughout the life span of a host remains largely understudied. Here, the fecal microbiota of conventionally raised C57BL/6J male mice was characterized throughout almost the entire adult life span, from "maturing" (9 weeks) until "very old" (112 weeks) age. Our results suggest that microbiota changes occur throughout life but are more pronounced in maturing to middle-age mice than in mice later in life. Phylum-level analysis indicates a shift of the Bacteroidota-to-Firmicutes ratio in favor of Firmicutes in old and very old mice. More Firmicutes amplicon sequence variants (ASVs) were transient with varying successional patterns than Bacteroidota ASVs, which varied primarily during maturation. Microbiota configurations from five defined life phases were used as training sets in a Bayesian model, which effectively enabled the prediction of host age. These results suggest that age-associated compositional differences may have considerable implications for the interpretation and comparability of animal model-based microbiome studies. The sensitivity of the age prediction to dietary perturbations was tested by applying this approach to two age-matched groups of C57BL/6J mice that were fed either a standard or western diet. The predicted age for the western diet-fed animals was on average 27 ± 11 (mean ± standard deviation) weeks older than that of standard diet-fed animals. This indicates that the fecal microbiota-based predicted age may be influenced not only by the host age and physiology but also potentially by other factors such as diet. IMPORTANCE The gut microbiome of a host changes with age. Cross-sectional studies demonstrate that microbiota of different age groups are distinct but do not demonstrate the temporal change that a longitudinal study is able to show. Here, we performed a longitudinal study of adult mice for over 2 years. We identified life stages where compositional changes were more dynamic and showed temporal changes for the more abundant species. Using a Bayesian model, we could reliably predict the life stages of the mice. Application of the same training set to mice fed different dietary regimens revealed that life-stage age predictions were possible for mice fed the same diet but less so for mice fed different diets. This study sheds light on the temporal changes that occur within the gut microbiota of laboratory mice over their life span and may inform researchers on the appropriate mouse age for their research.

Dataset Information

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

Publications

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

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