Medical College of Wisconsin
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Steroid sulfatase inhibitor DU-14 protects spatial memory and synaptic plasticity from disruption by amyloid β protein in male rats. Horm Behav 2016 Jul;83:83-92

Date

05/26/2016

Pubmed ID

27222435

DOI

10.1016/j.yhbeh.2016.05.019

Scopus ID

2-s2.0-84971245082 (requires institutional sign-in at Scopus site)   17 Citations

Abstract

Alzheimer's disease (AD) is an age-related mental disorder characterized by progressive loss of memory and multiple cognitive impairments. The overproduction and aggregation of Amyloid β protein (Aβ) in the brain, especially in the hippocampus, are closely involved in the memory loss in the patients with AD. Accumulating evidence indicates that the Aβ-induced imbalance of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) in the brain plays an important role in the AD pathogenesis and progression. The level of DHEA is elevated, while DHEAS is dramatically decreased in the AD brain. The present study tried to restore the balance between DHEA and DHEAS by using a non-steroidal sulfatase inhibitor DU-14, which increases endogenous DHEAS through preventing DHEAS converted back into DHEA. We found that: (1) DU-14 effectively attenuated the Aβ1-42-induced cognitive deficits in spatial learning and memory of rats in Morris water maze test; (2) DU-14 prevented Aβ1-42-induced decrease in the cholinergic theta rhythm of hippocampal local field potential (LFP) in the CA1 region; (3) DU-14 protected hippocampal synaptic plasticity against Aβ1-42-induced suppression of long term potentiation (LTP). These results provide evidence for the neuroprotective action of DU-14 against neurotoxic Aβ, suggesting that up-regulation of endogenous DHEAS by DU-14 could be beneficial to the alleviation of Aβ-induced impairments in spatial memory and synaptic plasticity.

Author List

Yue XH, Tong JQ, Wang ZJ, Zhang J, Liu X, Liu XJ, Cai HY, Qi JS

Author

Jiaqing Tong PhD Postdoctoral Researcher 3 in the Neurology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Alzheimer Disease
Amyloid beta-Peptides
Animals
Cognition Disorders
Hippocampus
Long-Term Potentiation
Male
Maze Learning
Memory Disorders
Neuronal Plasticity
Neuroprotective Agents
Rats
Rats, Sprague-Dawley
Spatial Memory
Steryl-Sulfatase
Tyramine
Up-Regulation