title: Oestrogen receptor α agonist improved long-term ovariectomy-induced spatial cognition deficit in young rats.
abstract: Ovariectomy is known as 'surgical menopause' with decreased levels of oestrogen in female rodents and its reported risks and adverse effects include cognitive impairment. In the brain, oestrogen exerts effects through its receptors, oestrogen receptor α (ERα) and β (ERβ). However, the role of ERα or ERβ in ovariectomy-induced cognitive impairment needs further investigation. Here, we observed that bilaterally ovariectomized 3-month-old rats showed obvious spatial learning and memory deficits in the Morris water maze with significant loss of neurons and synapses in the hippocampus. In addition to the rapid decline in serum oestradiol levels, the expression of ERα, but not ERβ, was decreased in the hippocampus starting 1 wk after ovariectomy. Prompt 4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (PPT) treatment (1 mg/kg.d), an agonist of ERα, improved the spatial learning and memory ability of ovariectomized rats and rescued ovariectomy-induced neuron loss by up-regulating the level of BCLxl, an important anti-apoptosis protein. Furthermore, PPT treatment also improved ovariectomy-induced hippocampal synapse loss and up-regulated the levels of synaptic proteins (synapsin I, NR2A and GluR1) and the activates of CaMK Πα, ERK and Akt. Thus, these results demonstrated that ERα plays an important role in neuroprotection and that prompt ERα rescue is effective to improve hippocampal-dependent cognition deficit after long-term ovariectomy.
authors.affiliation: Department of Pathology and Pathophysiology, Key Laboratory of Neurological Disease of National Education Ministry and Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Na
authors.initials: N
authors.lastname: Qu
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Zan-Chao
authors.initials: ZC
authors.lastname: Liu
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha / Q000819:agonists*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology / Q000627:therapeutic use*; D018782:Maze Learning / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010052:Ovariectomy / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012502:Sapogenins / Q000494:pharmacology / Q000627:therapeutic use*; D016622:Silver Staining; D013037:Spatial Behavior / Q000187:drug effects*; D013997:Time Factors
chemical_list: D047628:Estrogen Receptor alpha; D036145:Ginsenosides; D012502:Sapogenins; C507965:ginsenoside 20S-protopanaxatriol; D004958:Estradiol