Age-related progressive neuronal DNA damage associated with cerebral degeneration in a mouse model of accelerated senescence

The DNA of cerebral neurons in subjects with Alzheimer's disease is extensively damaged, although the morphological features of apoptosis are absent. We investigated whether DNA is damaged in the brains of the SAMP10 strain of mouse, in which accelerated senescence is characterized by age-related cerebral atrophy and cognitive impairment. We performed quantitative terminal deoxynucleotidyl transferase-mediated digoxigenin-labeled dUTP nick end labeling (TUNEL), using paraffin sections. TUNEL positive cells increased in number in the cerebral neurons of SAMP10 mice with aging. TUNEL positive cells were widely distributed in mice at age 13-14 months, and obvious in the olfactory tubercle, anterior cingulate cortex, insular cortex, and amygdala. These TUNEL positive cells did not have the morphological features of apoptosis. Therefore, the DNA became damaged with advancing age through a mechanism other than apoptosis. SAMP10 is a useful mouse model of brain aging that mimics the progressive neuronal DNA damage associated with human neurodegenerative disorders.