Localization of atrophy-prone areas in the aging mouse brain: Comparison between the brain atrophy model SAM-P/10 and the normal control SAM-R/1

Abstract

Mouse inbred strain “SAM-P/10” (Senescence Accelerated Mouse) is a model of age-related brain atrophy. In this strain there is an earlier and more severe age-related deterioration in the conditional avoidance learning than the normal control inbred SAM-R/1 strain. The present study analysed age-related changes in brain area size using a computerized morphometric method. The region most vulnerable to age-related atrophy in SAM-P/10 was the frontal region of the cerebral cortex, including the prefrontal cortex. Other neocortical regions underwent diffuse atrophy. Posterior piriform cortex, entorhinal cortex, anterior olfactory nucleus, amygdala, caudate-putamen, nucleus accumbens and cerebellar cortex were atrophy-prone regions. The septum also underwent atrophy but other basal forebrain structures were intact. The hippocampus, diencephalon and brainstem structures showed no atrophie change. White matter structures did not change in size with aging except for the forceps minor of the corpus callosum, which showed age-related atrophy. On the contrary, SAM-R/1 showed a significant age-related atrophy only in a restricted part of the cerebral cortex, mainly in the parietal region. Other cortical regions, subcortical structures, diencephalon, brainstem structures, cerebellum and white matter were atrophy-resistant in SAM-R/1. The prefrontal cortex, entorhinal cortex, piriform cortex and striatum are closely interconnected and also connect with the amygdala which plays a key role in conditioning in the rodent. Age-related atrophy in all these structures in SAM-P/10 presumably accounts for the age-related deficits in conditional avoidance learning in this strain of mouse. Comparison between SAM-P/10 and SAM-R/1 or other well-known rodents indicates that SAM-P/10 is a unique rodent that spontaneously and rapidly develops progressive generalized cerebral atrophy, which is considered to be a pathological process rather than an accelerated aging process.