Page 83 - AN-2-3

Advanced Neurology

ORIGINAL RESEARCH ARTICLE
Cognition damage due to disruption of cyclic

adenosine monophosphate-related signaling
pathway in melatonin receptor 2 knockout mice

3
2†
He-Zhou Huang , Xiang Wang , and Dan Liu *
1†
1 Department of Pathophysiology, Key Laboratory of Neurological Disorders of the Education Ministry,
School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology,
Wuhan, China
2 Department of Histology and Embryology, Medical College, Jianghan University, Wuhan, China
3 Department of Genetics, School of Basic Medicine, Tongji Medical College, Huazhong University of
Science and Technology, Wuhan, China

Abstract

Alzheimer’s disease (AD) was characterized by the presence of neurofibrillary tangles
and senile plaques. Although melatonin plays an important role in AD, its mechanism
is still unknown. In this study, we found obvious cognition damage in melatonin
receptor 2 knockout mice (MT2KO) and double knockout mice (DKO), but not in
melatonin receptor 1 knockout mice (MT1KO). To explore the mechanism in-depth, we
attempted to determine the levels of metabolites and amyloid-β peptide (Aβ). A high
† These authors contributed equally level of Cho/tCr (choline/total creatine) was detected in MT2KO and MT1KO by nuclear
to this work. magnetic resonance (NMR), while a high level of myo-inositol/total creatine (mI/tCr)
*Corresponding author: was only detected in MT1KO. A higher ratio of Aβ42/40 was found in MT2KO, but not
Dan Liu in MT1KO and DKO. We also found an abnormal increase of plaque detected by the
(liudan_echo@mail.hust.edu.cn)
A3981 antibody in MT2KO and DKO. Furthermore, a huge decrease of postsynapses
Citation: Huang H, Wang X, Liu was confirmed in MT2KO and DKO, but not MT1KO, accompanied by a low level of
D, 2023, Cognition damage due
to disruption of cyclic adenosine phosphorylated cyclic adenosine monophosphate (cAMP) response element-binding
monophosphate-related signaling protein (CREB) at the site of serine 133 and a low activity of protein kinase A. Finally,
pathway in melatonin receptor 2 the cAMP, cyclic guanosine monophosphate, and cAMP-regulated guanine nucleotide
knockout mice. Adv Neuro, 2(3):
0974. exchange factor (EPAC) were detected. We observed a significant decrease of cAMP
https://doi.org/10.36922/an.0974 and EPAC2 in MT2KO, but not MT1KO. Thus, we identified that cAMP-related signaling
Received: May 22, 2023 pathway was disturbed in MT2KO and was critical for normal cognitive function.
Accepted: July 13, 2023
Keywords: Melatonin receptor 2; Plaque; Cyclic adenosine monophosphate; cAMP
Published Online: August 11, 2023
response element-binding; Cognition
Copyright: © 2023 Author(s).
This is an Open-Access article
distributed under the terms of the
Creative Commons Attribution
License, permitting distribution, 1. Introduction
and reproduction in any medium,
provided the original work is Melatonin (N-acetyl-5-methoxy tryptamine, MT) was synthesized by the pineal gland,
properly cited. and its level was controlled by circadian rhythms. Melatonin plays a role in its signal
Publisher’s Note: AccScience transduction and acts as an antioxidant. Melatonin receptor is divided into two types:
Publishing remains neutral with Melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). Both of them were
regard to jurisdictional claims in
published maps and institutional G-protein-coupled receptors, which can activate protein kinase A (PKA), but their
[1]
affiliations. signal transduction is fundamentally different .

Volume 2 Issue 3 (2023) 1 https://doi.org/10.36922/an.0974