Protective Effect of 17β-Estradiol Upon Hippocampal Spine Density and Cognitive Function in an Animal Model of Vascular Dementia

Ying Zhu, Quanguang Zhang, Wenli Zhang, Ning Li, Yongxin Dai, Jingyi Tu, Fang Yang, Darrell W Brann, Ruimin Wang

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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.

Original languageEnglish (US)
Article number42660
JournalScientific Reports
Volume7
DOIs
StatePublished - Feb 16 2017

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Vascular Dementia
Common Carotid Artery
Cognition
Estradiol
Spine
Animal Models
Dementia
Hippocampal CA1 Region
Serum Amyloid A Protein
Dendritic Spines
Synaptophysin
Neuronal Plasticity
Agaricales
Amyloid beta-Peptides
Oligodendroglia
Myelin Sheath
Ubiquitin
Sprague Dawley Rats
Hippocampus
Proteins

ASJC Scopus subject areas

  • General

Cite this

Protective Effect of 17β-Estradiol Upon Hippocampal Spine Density and Cognitive Function in an Animal Model of Vascular Dementia. / Zhu, Ying; Zhang, Quanguang; Zhang, Wenli; Li, Ning; Dai, Yongxin; Tu, Jingyi; Yang, Fang; Brann, Darrell W; Wang, Ruimin.

In: Scientific Reports, Vol. 7, 42660, 16.02.2017.

Research output: Contribution to journalArticle

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