Differential impairment of spatial and nonspatial cognition in a mouse model of brain aging

Wei Wang, Song Li, Hui ping Dong, Shen Lv, Yi yuan Tang

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Abstract

Aims: Chronic exposure to d-galactose (D-Gal), which causes acceleration in aging and simulated symptoms of natural senescence, has been used as a reliable animal model of aging. However, the different influences of D-Gal on spatial and nonspatial cognition are as yet unclear. Main methods: In the present study, the object recognition test (ORT), object location test (OLT) and Y-maze test were carried out to assess the cognitive performance of mice after 8 weeks of chronic D-Gal exposure. The expression of oxidative-stress biomarkers in the prefrontal cortex (PFC) and caspase-3 in the hippocampus (HIP) were also determined. Key findings: The results of the behavioral tests indicated that after chronic D-Gal exposure, the spatial memory of mice was seriously impaired, whereas nonspatial cognition remained intact. D-Gal exposure also induced more significant changes in malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activities in the HIP than in the PFC. Furthermore, chronic D-Gal exposure triggered more substantial caspase-3 overexpression in the HIP than in the PFC. Significance: Together, these findings suggest the impairment of spatial, but not nonspatial, cognitive ability after chronic D-Gal exposure. The differential nature of this impairment might be due to the more substantial reduction of antioxidant enzyme activities and more severe neuronal apoptosis mediated by caspase-3 in the HIP. The present results also indicate that the HIP and HIP-dependent spatial cognition might be more susceptible to oxidative stress during senescence or other pathological processes.

Original languageEnglish
Pages (from-to)127-135
Number of pages9
JournalLife Sciences
Volume85
Issue number3-4
DOIs
StatePublished - Jul 15 2009

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Keywords

  • Antioxidant enzyme
  • Caspase-3
  • Nonspatial cognition
  • Spatial cognition
  • d-galactose

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