br Introduction Clinical manifestations of

Introduction Clinical manifestations of Alzheimer's disease (AD) are mainly characterized by progressive intellectual deterioration, memory impairment, cognitive impairment, and psychiatric symptoms. The pathogenesis of AD remains unclear, mainly containing genetic factors, neurotransmitter disorders, cytoskeletal changes, hypertension, diabetes, hyperlipemia, high serum homocysteine, central obesity, atrial fibrillation, traumatic brain injury, chronic viral infection, low educational level, smoking, and history of exposure to heavy metals. Tau protein phosphorylation can reduce the ability of microtubule assembly and damage nerve cells. Aging can cause the phosphorylation of Tau protein at multiple sites. Recent studies suggested that the disorders of energy metabolism may be one of pathogenesis of AD, mainly because AD patients often suffer from visceral fat accumulation, insulin resistance and abnormal secretion of leptin and APN. APN, an adipokine secreted by adipose tissue, is involved in the regulation of energy metabolism, enhances insulin sensitivity, glucose uptake and fatty this oxidation, effectively resists inflammation and atherosclerosis, and protects vascular endothelial cells. The decrease in circulating APN levels is correlated with insulin resistance syndrome and visceral fat deposition, and can be found in some clinical diseases, such as obesity, dyslipidemia, diabetes and depression. APN and its receptors are widely expressed in the brain. AdipoR1 is mainly expressed in the hippocampus. Combining with diverse physiological functions of APN, it is indicated that APN signaling system may exert a crucial effect on cognitive function. Teixeira et al confirmed that low circulating APN levels were associated with cognitive dysfunction, and the decrease in APN levels could reflect the pathological process of AD. On the contrary, Kamogawa et al verified that the increase in plasma APN levels was a protective factor for dementia in males, but did not impact cognitive function in females after the investigation in 517 community members, which was consistent with Une et al’s study. Roberts et al suggested that no significant difference in circulating APN levels was visible between mild cognitive impairment (MCI) patients and controls. Interestingly, the results of van Himbergen et al’s study are contrary to above results. They believed that the increase in circulating APN levels was an independent risk factor for dementia or AD in females, which was contrary to multiple physiological functions of APN. Another previous study showed that circulating APN levels had obvious sex difference, and the levels were higher in females than in males. Thus, APN levels may be affected by estrogen levels. Therefore, it is presumed that results of van Himbergen et al’s study were probably associated with estrogen levels in females. Pakaski et al demonstrated that serum APN levels increased progressively with the time of taking donepezil in AD patients, and also indirectly verified that APN had protective effects on AD patients. Accordingly, current results support the protective effect of on cognitive function. There is extensive cross-linking on the pathogenesis of AD and type II diabetes, which associates with aging. More and more studies have shown that APN may be the key point of their cross-linking. Age-associated degenerative lesions have been shown to accelerate the pathological process of AD and other neurodegenerative diseases. Taken together, we assumed that Alzheimer-like changes in the brain may be accompanied by the changes in APN and its receptor expression in aging process. This study sought to investigate the effects of aging on serum APN levels, APN and AdipoR1 expression in the rat brain.
Materials and methods
Results
Discussion Tau protein is a microtubule-associated protein widely expressed in the nervous system, promotes microtubule formation and stabilizes microtubule structure. Hyperphosphorylated Tau protein decreases its binding capacity to microtubules, so Tau protein cannot play a role in stabilizing microtubules, thereby damaging nerve cells. Hyperphosphorylated Tau protein accumulated in cells is a structural basis for neurofibrillary tangle formation, and neurofibrillary tangle is a marker of pathological changes in AD. Therefore, to verify whether aging rats can simulate the pathological process of AD, the present study identified total Tau protein (Tau5) and phosphorylated Tau protein (phosphorylation at Ser262 and Ser396). Our results demonstrated that no significant difference in Tau5 protein was observed in the cerebral cortex and hippocampus during aging. Moreover, there was no significant difference in the phosphorylation of Tau protein at Ser262 and Ser396 in the cerebral cortex. However, phosphorylation of Tau protein at Ser262 and Ser396 in the cognition-related hippocampus increased with age, which was consistent with Jung et al’s study. Taken together, aging is accompanied by AD-like degeneration in the region associated with cognitive function. In this study, APN and its receptor expression during aging could indirectly reflect the relationship of AD-like degeneration with APN and its receptor expression.