Related Experiment Video
Updated: Jun 11, 2026
Orthotopic Ovarian Transplantation Procedures to Investigate the Life- and Health-span Influence of Ovarian Senescence in Female Mice
Published on: February 12, 2018
Long-term deprivation of gonadal hormone accelerates brain aging in mice
Yan Hou1, Xiu-Qi Bao, Huai-Ling Wei
1Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Objective:
The purpose of this study was to assess the effect of long-term deprivation of gonadal hormone on brain aging in mice to develop a model of gonadectomy-accelerated brain aging.
Methods:
Male and female mice at 2 months old were orchiectomized (ORX) or ovarectomized (OVX) bilaterally or sham operated, and then they were fed for 10 months. The spatial learning and memory ability was tested using Morris Water Maze. The biomarkers of brain neuropathology were examined by Western blotting and immunohistochemistry.
Results:
Ovarectomy mildly impaired spatial learning and memory of mice, while the impairment in ORX-mice was not significant. The amount of Nissl bodies decreased in the hippocampus and cortex of gonadectomied mice. The expression of beta-amyloid (Aβ), beta-site APP cleaving enzyme 1 and phosphorylated-Tau increased in gonadectomied mice. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) decreased in the brain of OVX-mice, but neurotrophin-3 (NT-3) showed no change. We detected no decrease of NGF, BDNF or NT-3 in ORX-mice. TrkA expression decreased and p75(NTR) increased in the brain of gonadectomied mice. In all the above tests, there were no significant differences between young (2 months old) and sham operated (12 months old) mice. Alternations in the brain aging parameters were more obvious in OVX-mice than in ORX-mice.
Conclusion:
Long-term gonadal hormone deprivation by young-age gonadectomy accelerated mouse brain aging, which could serve as a valuable mouse model to study brain aging and aging-related pathological changes.
Insights
Long-term gonadal hormone deprivation accelerates brain aging in mice, particularly in females after ovarectomy. This study establishes a valuable mouse model for investigating age-related brain changes and neuropathology.
Area of Science:
- Neuroscience
- Endocrinology
- Aging Research
Background:
- Gonadal hormones play a crucial role in brain function and development.
- Age-related cognitive decline and neuropathology are significant health concerns.
- Understanding the impact of hormone deprivation on brain aging is essential for developing therapeutic strategies.
Purpose of the Study:
- To investigate the long-term effects of gonadal hormone deprivation on brain aging in a mouse model.
- To establish a gonadectomy-accelerated brain aging model for further research.
- To compare the effects of orchiectomy (ORX) and ovarectomy (OVX) on cognitive function and neuropathological markers.
Main Methods:
- Male and female mice underwent bilateral orchiectomy (ORX) or ovarectomy (OVX) or sham surgery at 2 months of age and were studied for 10 months.
- Spatial learning and memory were assessed using the Morris Water Maze.
- Brain neuropathology biomarkers, including Nissl bodies, beta-amyloid (Aβ), phosphorylated-Tau, and neurotrophic factors (NGF, BDNF, NT-3), were analyzed via Western blotting and immunohistochemistry.
Main Results:
- Ovarectomy (OVX) mildly impaired spatial learning and memory; orchiectomy (ORX) showed non-significant impairment.
- Gonadectomy led to decreased Nissl bodies in the hippocampus and cortex.
- Increased expression of beta-amyloid (Aβ) and phosphorylated-Tau was observed in gonadectomized mice.
- Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) decreased in OVX mice but not in ORX mice.
- TrkA expression decreased while p75(NTR) increased in gonadectomized mice brains.
- Changes were more pronounced in OVX mice compared to ORX mice.
Conclusions:
- Long-term gonadal hormone deprivation induced by gonadectomy in young mice accelerates brain aging.
- The gonadectomy-induced brain aging model is valuable for studying age-related cognitive decline and neuropathological changes.
- Ovarectomy appears to have a more significant impact on brain aging markers than orchiectomy in this model.
Related Concept Videos
01:28Menopause
01:26Aging
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...