Bcl-2 over-expression fails to prevent age-related loss of calretinin positive neurons in the mouse dentate gyrus.
BACKGROUND
Cognitive performance declines with increasing age. Possible cellular mechanisms underlying this age-related functional decline remain incompletely understood. Early studies attributed this functional decline to age-related neuronal loss. Subsequent studies using unbiased stereological techniques found little or no neuronal loss during aging. However, studies using specific cellular markers found age-related loss of specific neuronal types. To test whether there is age-related loss of specific neuronal populations in the hippocampus, and subsequently, whether over-expression of the B-cell lymphoma protein-2 (Bcl-2) in these neurons could delay possible age-related neuronal loss, we examined calretinin (CR) positive neurons in the mouse dentate gyrus during aging.


RESULTS
In normal mice, there was an age-related loss of CR positive cells in the dentate gyrus. At the same region, there was no significant decrease of total numbers of neurons, which suggested that age-related loss of CR positive cells was due to the decrease of CR expression in these cells instead of cell death. In the transgenic mouse line over-expressing Bcl-2 in neurons, there was an age-related loss of CR positive cells. Interestingly, there was also an age-related neuronal loss in this transgenic mouse line.


CONCLUSIONS
These data suggest an age-related loss of CR positive neurons but not total neuronal loss in normal mice and this age-related neuronal change is not prevented by Bcl-2 over-expression.
Han
Mingbo
M
Department of Otolaryngology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA. hanm@ent.wustl.edu
Schottler
Frank
F
Lei
Debin
D
Dong
Elizabeth Y
EY
Bryan
Alexander
A
Bao
Jianxin
J