Alzheimer's disease (AD) is the leading cause of dementia and has become an important public health concern. Accumulating evidence indicates that estradiol can both facilitate and impair memory-related processes and, as a result, the precise nature of the role that estradiol plays during AD pathology remains elusive. Therefore, the present study established a mouse model of AD using stereotactic brain injection of Aβ in which the mice were bilaterally ovariectomized to investigate the effects of 17β-estradiol (E2) treatment during different stages of the AD process (early and late stages). The cognitive deficits associated with this AD model were significantly ameliorated, and there was a significant increase in hippocampal neurogenesis in Aβ mice that received E2 treatment during the early stage of AD pathology. On the other hand, Aβ mice that received E2 treatment during the late stage of AD pathology did not exhibit any improvements in cognitive function or hippocampal neurogenesis. To reveal the mechanisms, underlying these effects, levels of oxidative stress, activity in death-associated pathways, gliosis, and synaptic function were assessed in the hippocampus. The Aβ mice that received E2 treatment during the early stage of AD pathology exhibited significant reductions in the production of nitric oxide (NO) and reactive oxygen species (ROS), a marked decrease in the activation of Cytochrome-c/Bax/Bcl-2/caspase-3 pathway, a notable decrease in the level of gliosis a significant increase in the number of synapses (ultrastructural investigation), and a marked upregulation in synaptic function-related proteins compared to mice that received E2 treatment during the late stage of AD pathology. Taken together, these findings indicate that E2 treatment during the early stage of AD pathology might be an efficient approach to ameliorate the development of this disease.
Clinical observation and following-up results revealed that minimally invasive drainage treatment was superior to internal medical treatment and craniotomy.
We investigated the protective effects and mechanism of TPX2 on apoptosis of rat neurocytes. A total of 90 SD rats were randomly divided into the drug group, the control group and the blank group, with 30 rats in each group. The rats in the drug group and in the blank group were anesthetized with 10% chloral hydrate (at the dose of 0.5 ml/100 g) and Aβ1–42, with the concentration of 5 µl (1 µg/µl), was injected in the exact position of bilateral hippocampal areas of rats to establish the model. The configured TPX2 inhibitors and edible benne oil were mixed and made into a suspension. After model establishment, the rats were given different treatment methods; the rats in the drug group were given gavage administration in the proportion of 75 mg/kg once a day. The rats in the control group were given intragastric administration with the same proportion of physiological saline once a day. The blank group was the normal healthy group and the rats in this group did not undergo any surgery or drug treatment. Brain tissue in rats were divided into two parts, one part was fixed, dehydrated, paraffin-embedded and made into slices of approximately 5 µm. TUNEL staining was used to examine the apoptosis of brain tissue, H&E staining was used to observe the brain tissue cells of each group, and western blotting for detecting the MAPK, Erk and expression levels of p38 and RT-polymerase chain reaction method was employed to examine mRNA expression levels of MAPK, Erk and p21. After one week, TUNEL staining showed that apoptosis of brain tissue in the drug group was significantly greater than those of the control and blank groups. The protein expression levels of MAPK, Erk and p38 were significantly higher than those of the control group and the normal healthy group; the differences were statistically significant (P<0.05). Western blotting showed that the protein expression levels of MAPK, Erk and p38 of the drug group were significantly lower than those of the control group but higher than those of the normal healthy group; the differences were statistically significant (P<0.05). TPX2 has a protective effect on the apoptosis of brain tissue processed by Aβ1–42, which plays its role through the inhibition of the protein expression levels of MAPK, Erk and p38.
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