Long-term D-galactose injection combined with ovariectomy serves as a new rodent model for Alzheimer's disease.
Estrogen deprivation and oxidative stress have been well established as two main factors closely related to the pathological development of Alzheimer's disease (AD). The aim of the present study is to investigate whether these two components act synergistically to accelerate the pathophysiological course of AD. To do this, we examined the effect of long-term intraperitoneal administration of D-galactose (D-gal) into ovariectomized (OVX) rats. Six weeks later, the OVX and d-gal-injected rats exhibited a higher degree of cognitive and memory impairment. This was accompanied by cholinergic neuronal loss in the forebrain and synaptic degeneration in the hippocampus and cerebral cortex which was not observed in intact controls, animals receiving injections of d-gal alone, untreated OVX animals or OVX animals receiving both D-gal and 17-beta estradiol. The typical histopathological alterations associated with AD, including intracellular deposition of amyloid beta peptide and the appearance of intracellular neurofibrillary tangles and nuclear granulovacuolar bodies, were observed in the hippocampus of OVX and D-gal-injected rats but not in other control groups. These results strongly suggest that estrogen deprivation and oxidative stress behave synergistically to enhance the development and progression of AD. Long-term OVX combined with D-gal injection serves as an ideal AD rodent model capable of mimicking pathological, neurochemical and behavioral alterations in AD.
Hua
Xiangdong
X
Department of Human Anatomy, Histology and Embryology, Institute of Neurosciences, Nanjing Medical University, Nanjing, 210029 China.
Lei
Ming
M
Zhang
Yongjie
Y
Ding
Jiong
J
Han
Qunying
Q
Hu
Gang
G
Xiao
Ming
M
D000544:Alzheimer Disease / Q000139:chemically induced* / Q000209:etiology / Q000473:pathology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D005690:Galactose / Q000633:toxicity*; D009448:Neurochemistry / Q000706:statistics & numerical data; D010052:Ovariectomy / Q000009:adverse effects*; D051381:Rats / Q000601:surgery; D017207:Rats, Sprague-Dawley
D005690:Galactose