Effects of ovarian hormone loss on neuritic plaques and autophagic flux in the brains of adult female APP/PS1 double-transgenic mice
| Autor: | Min Luo, Qiuhui Yao, Shifang Luo, Zhimin Long, Kejian Wang, Guiqiong He, Min Feng, Bo Yang |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genetically modified mouse medicine.medical_specialty autophagy Transgene Ovariectomy Biophysics Autophagy-Related Proteins Mice Transgenic Plaque Amyloid Biology transgenic mice Biochemistry Cathepsin B Pathogenesis 03 medical and health sciences Amyloid beta-Protein Precursor 0302 clinical medicine Alzheimer Disease Internal medicine medicine Presenilin-1 Animals Humans Senile plaques Gonadal Steroid Hormones LAMP1 Autophagy Ovary Brain General Medicine neuritic plaques Disease Models Animal 030104 developmental biology Endocrinology Female Original Article Alzheimer’s disease 030217 neurology & neurosurgery Hormone |
| Zdroj: | Acta Biochimica et Biophysica Sinica |
| ISSN: | 1745-7270 |
| Popis: | Epidemiologic studies have demonstrated that women account for two-thirds of Alzheimer’s disease (AD) cases, for which the decline in circulating gonadal hormone is considered to be one of the major risk factors. In addition, ovarian hormone deficiency may affect β-amyloid (Aβ) deposition, which has a close relationship with autophagic flux. In this study, we investigated the impact of short-term or long-term ovarian hormone deprivation on two mouse models, the non-transgenic (wild-type) and the APP/PS1 double-transgenic AD (2×TgAD) model. Autophagy-related proteins (Beclin1, LC3, and p62) and lysosome-related proteins were detected to evaluate Aβ deposition and autophagy. Our results showed that in the group with short-term depletion of ovarian hormones by ovariectomy (ovx), Beclin1, Cathepsin B (Cath-B), and LAMP1 levels were significantly decreased, while the levels of LC3-II and p62 were increased. In the long-term group, however, there was a sharp decline in Beclin1, LC3-II, Cath-B, and LAMP1 expression but not in p62 expression which is increased. It is worthwhile to note that the occurrence of neuritic plaque-induced ovarian hormone loss increased both the Aβ level and neuritic plaque deposition in 2×TgAD mice. Therefore, autophagy may play an important role in the pathogenesis of female AD, which is also expected to help post-menopausal patients with AD. |
| Databáze: | OpenAIRE |
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