To verify whether circulating APN could protect cognitive

To verify whether circulating APN could protect cognitive function during aging, we detected the alterations in circulating adipoenctin levels in aging rats. Our results suggested that circulating APN levels reduced with age. Kawasumi et al’s study results are consistent with ours. They concluded that circulating APN levels were remarkably lower in dogs aged 8–12 years than dogs aged 0–7 years. Nevertheless, previous results are contrary, and other studies did not show noticeable difference in APN levels during aging. To find out the reason, Li et al detected circulating APN levels in mice aged 2, 6 and 24 months, although no significant difference was detected in APN levels. Considering the increased fat content induced by aging, Li et al identified the ratio of plasma APN levels to visceral fat content, and confirmed that above ratio was diminished with age. Tomicek et al confirmed that circulating APN levels were higher in 6-month rats than in 24-month rats, and ovariectomy reduced APN levels. These results indicated that circulating APN levels in perimenopause could be impacted by estrogen. Matsui et al verified that circulating APN levels in females showed “U” shape during aging, and were positively correlated with aging in postmenopause, and negatively correlated with age in early menopause. Riestra et al verified that APN levels were positively associated with sex hormone-binding globulin levels. Numerous studies demonstrated that circulating APN levels were greater in females than in males, but they did not conduct any analysis in different stages of menopause. Furthermore, during the analysis, they considered the effects of sex hormone-binding globulin levels. Thus, above studies may not precisely reflect the changes in APN expression in aging females. To exclude the significant interference of brincidofovir on study results, we selected male rats as materials. Our results confirmed that circulating APN levels reduced with age, indicating that APN probably played an important role in aging-related diseases. To further investigate the correlation of APN and its receptor with age-related cognitive dysfunction, this study investigated APN and its receptor expression in the brain of aging rats. Our results showed that with age, APN expression diminished in the hippocampus, but did not apparently alter in the cerebral cortex, which suggested that APN may be associated with cognitive function. Animal experiments showed that atorvastatin reduced oxidative stress in amyloid precursor protein-Tg mice, and accompanied by the increase in circulating APN levels.In vivo and in vitro studies further verified that APN lessened Aβ-induced neurotoxicity by antagonizing oxidative stress. Miao et al thought that the effects of APN overexpression on improving neurological rehabilitation in elder mice of cerebral ischemia were better than that in young mice, which also confirmed our view. With the aging process, decreased APN levels possibly played a key role in dementia-like pathological process in the elderly. Results from this study also demonstrated that a trend for AdipoR1 expression is consistent between cerebral cortex and hippocampus, which is positively associated with aging. AdipoR1 and AdipoR2 were expressed in the brain. Coope et al further verified that AdipoR1 and AdipoR2 can simultaneously express in the hypothalamus, but APN role produced by the hypothalamus depends on AdipoR1, but not on AdipoR2. Therefore, this study observed AdipoR1 changes in the brain with age, but did not detect AdipoR2. Sakr et al suggested that memory function reduced in diabetic rats, accompanied by decreased AdipoR1 in the hypothalamus. Sitagliptin can be used to treat diabetes, and improves memory function and upregulates AdipoR1 mRNA expression. It can be seen that AdipoR1 may play a role in pathological process of AD. However, our results are contrary to theirs. AdipoR1 expression increased in aging rats. APN receptor expression in the hypothalamus could be regulated by many factors such as energy metabolism. It remains unclear whether an increase in AdipoR1 expression in the brain with age is a negative feedback regulation induced by decreased APN expression, or a pathological process of aging, which deserves further investigation.