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


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.


RESULTS
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.


CONCLUSIONS
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.
Wang
Wei
W
Laboratory of Brain and Mind, Institute of Neuroinformatics, Dalian University of Technology, 116024, Dalian, China.
Li
Song
S
Dong
Hui-Ping
HP
Lv
Shen
S
Tang
Yi-Yuan
YY
D000375:Aging / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D005690:Galactose / Q000633:toxicity; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning; D051379:Mice; D010364:Pattern Recognition, Visual / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000378:metabolism
D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; D053148:Caspase 3; D005690:Galactose