Open AccessConstipation in Tg2576 mice model for Alzheimer’s disease associated with dysregulation of mechanism involving the mAChR signaling pathway and ER stress response
Author(s) -
Ji Eun Kim,
Jin Ju Park,
Mi Rim Lee,
Jun Young Choi,
Bo Song,
Ji Won Park,
Mi Ju Kang,
Hyeon Son,
Jin Tae Hong,
Dae Youn Hwang
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0215205
Subject(s) - unfolded protein response , medicine , constipation , endocrinology , hippocampus , muscarinic acetylcholine receptor , endoplasmic reticulum , muscarinic agonist , pathology , neuroscience , receptor , biology , microbiology and biotechnology
Background Although constipation has been researched in various neurological disorders, including Parkinson’s disease (PD) and spinal cord injury (SCI), the pathological mechanism of this symptom has not been investigated in Alzheimer’s disease (AD) associated with loss of nerve cells in the brain. This study was undertaken to gain scientific evidences for a molecular correlation between constipation and AD. Methods To understand the etiology, we measured alterations in various constipation parameters, muscarinic acetylcholine receptors (mAChRs) and endoplasmic reticulum (ER) stress response, in 11-month-old Tg2576 transgenic (Tg) mice showing AD-like phenotypes. Results A high accumulation of amyloid beta (Aβ) peptides, a key marker of AD pathology, were detected in the cortex and hippocampus of Tg mice. Furthermore, significant alterations were observed in various constipation parameters including stool weight, histological structure, cytological structure and mucin secretion in Tg2576 mice. Moreover, M2 and M3 expression and the downstream signaling pathways of mAChRs were decreased in the Tg group, as compared with non-Tg (NT) group. Furthermore, activation of ER stress proteins and alteration of ER structure were also detected in the same group. Conclusions The results of the present study provide strong novel evidence that the neuropathological constipation detected in Tg2576 mice is linked to dysregulation of the mAChR signaling pathways and ER stress response.