title: Protective Effect of 17β-Estradiol Upon Hippocampal Spine Density and Cognitive Function in an Animal Model of Vascular Dementia.
abstract: The current study examined whether the steroid hormone, 17β-estradiol (E2) can exert long-lasting beneficial effects upon axonal health, synaptic plasticity, dementia-related amyloid-beta (Aβ) protein expression, and hippocampal-dependent cognitive function in an animal model of chronic cerebral hypoperfusion and vascular dementia (VaD). Chronic cerebral hypoperfusion and VaD was induced by bilateral common carotid artery occlusion (BCCAO) in adult male Sprague Dawley rats. Low dose E2 administered for the first 3-months after BCCAO exerted long-lasting beneficial effects, including significant neuroprotection of hippocampal CA1 neurons and preservation of hippocampal-dependent cognitive function when examined at 6-months after BCCAO. E2 treatment also prevented BCCAO-induced damage to hippocampal myelin sheaths and oligodendrocytes, enhanced expression of the synaptic proteins synaptophysin and PSD95 in the hippocampus, and prevented BCCAO-induced loss of total and mushroom dendritic spines in the hippocampal CA1 region. Furthermore, E2-treatment also reduced BCCAO induction of dementia-related proteins expression such as p-tau (PHF1), total ubiquitin, and Aβ1-42, when examined at 6 m after BCCAO. Taken as a whole, the results suggest that low-dose E2 replacement might be a potentially promising therapeutic modality to attenuate or block negative neurological consequences of chronic cerebral hypoperfusion and VaD.
authors.affiliation: Neurobiology Institute of Medical Research Center, International Science &Technology Cooperation Base of Geriatric Medicine, North China University of Science and Technology, Tangshan 063000, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta 30912, USA.
authors.forename: Quanguang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Neurobiology Institute of Medical Research Center, International Science &Technology Cooperation Base of Geriatric Medicine, North China University of Science and Technology, Tangshan 063000, China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Neurobiology Institute of Medical Research Center, International Science &Technology Cooperation Base of Geriatric Medicine, North China University of Science and Technology, Tangshan 063000, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Neurobiology Institute of Medical Research Center, International Science &Technology Cooperation Base of Geriatric Medicine, North China University of Science and Technology, Tangshan 063000, China.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Neurobiology Institute of Medical Research Center, International Science &Technology Cooperation Base of Geriatric Medicine, North China University of Science and Technology, Tangshan 063000, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Tu
authors.affiliation: Neurobiology Institute of Medical Research Center, International Science &Technology Cooperation Base of Geriatric Medicine, North China University of Science and Technology, Tangshan 063000, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta 30912, USA.
authors.forename: Darrell W
authors.initials: DW
authors.lastname: Brann
authors.affiliation: Neurobiology Institute of Medical Research Center, International Science &Technology Cooperation Base of Geriatric Medicine, North China University of Science and Technology, Tangshan 063000, China.
authors.forename: Ruimin
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D015415:Biomarkers; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000378:metabolism; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D015140:Dementia, Vascular / Q000188:drug therapy / Q000473:pathology / Q000523:psychology*; D049229:Dendritic Spines / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D065852:Spatial Memory / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018696:Neuroprotective Agents; D004958:Estradiol