Long-term deprivation of gonadal hormone accelerates brain aging in mice.
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.


CONCLUSIONS
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.
Hou
Yan
Y
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Bao
Xiu-Qi
XQ
Wei
Huai-Ling
HL
Luo
Yuan
Y
Liu
Geng-Tao
GT
D000375:Aging / Q000378:metabolism* / Q000523:psychology*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor; D005260:Female; D042341:Gonadal Hormones / Q000009:adverse effects / Q000172:deficiency*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D009414:Nerve Growth Factors / Q000378:metabolism; D009919:Orchiectomy / Q000523:psychology; D010052:Ovariectomy / Q000523:psychology; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D042341:Gonadal Hormones; D009414:Nerve Growth Factors; D020800:Receptor, Nerve Growth Factor; D016875:tau Proteins; D020917:Receptor, trkA; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse