Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Hyaluronic Acid-Conjugated 17β-Estradiol Provide More Effectively to Alleviate Estropause-Induced Cognitive Deficits in Rats

Mu-Hsuan Chen
ORCID logo ,
Hsiao-Chun Lin
,
Tzu Chao
,
Viola Szu-Yuan Lee
,
Chia-Lung Hou
,
Tsyr-Jiuan Wang
,
Jeng-Rung Chen
* ORCID logo
Version 1 : Received: 2 October 2023 / Approved: 2 October 2023 / Online: 2 October 2023 (10:32:03 CEST)

A peer-reviewed article of this Preprint also exists.

Chen, M.-H.; Lin, H.-C.; Chao, T.; Lee, V.S.-Y.; Hou, C.-L.; Wang, T.-J.; Chen, J.-R. Hyaluronic Acid Conjugated with 17β-Estradiol Effectively Alleviates Estropause-Induced Cognitive Deficits in Rats. Int. J. Mol. Sci. 2023, 24, 15569. Chen, M.-H.; Lin, H.-C.; Chao, T.; Lee, V.S.-Y.; Hou, C.-L.; Wang, T.-J.; Chen, J.-R. Hyaluronic Acid Conjugated with 17β-Estradiol Effectively Alleviates Estropause-Induced Cognitive Deficits in Rats. Int. J. Mol. Sci. 2023, 24, 15569.

Abstract

Women are at higher risk of cognitive impairment and Alzheimer’s disease (AD) after menopause when the estrous cycle becomes irregular and begins to taper off. Numerous studies have shown that estrogen deficiency, especially estradiol (E2), has been shown to play a key role in this phenomenon. Recently, a novel polymeric drug, hyaluronic acid-17β-Estradiol conjugate (HA-E2), has been developed which has the ability to cross the blood-brain barrier (BBB), facilitate a longer E2 release profile and lower risk of estrogen supplement related side effects. In this study, we used an ovariohysterectomy (OHE) rat model of postmenopausal cognitive deficits and explore whether HA-E2 treatment can improve the cholinergic septo-hippocampal innervation system, synaptic transmission in the hippocampal pyramidal neuron and cognitive impairment. Our results show that OHE rats after HA-E2 administration have increased expression of choline acetyltransferase (ChAT) in the medial septal nucleus (MS nucleus) and the hippocampus, increased spine density in hippocampal pyramidal neurons, and improved spatial learning and memory. Therefore, HA-E2 has great potential as a new novel class of drugs for estrogen-deficiency-induced cognitive impairment and AD.

Keywords

Cognitive deficit; Alzheimer’s disease; Cholinergic septo-hippocampal innervation system; Dendritic spine; Hippocampus; Morris water maze

Subject

Biology and Life Sciences, Neuroscience and Neurology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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