Time-course profiling of behavioral phenotypes and Ywhah/ERK signaling expression within the vestibular region of the brainstem during motion sickness habituation
- 1Anhui Medical University
- 2Air Force Medical Center, PLA
Abstract
Motion sickness habituation represents a core neuroplastic model for investigating vestibular disorder adaptation, yet its brain-region-specific temporal molecular mechanisms remain poorly defined. Here, we adopted multi-brain-region proteomic screening combined with time-series molecular validation to characterize key molecular dynamics during motion sickness habituation. Adult mice received 15 consecutive days of sinusoidal rotational stimulation, and model establishment was verified via four behavioral indices. A self-constructed five-dimensional weighted scoring system based on proteomic data confirmed that the vestibular region of the brainstem exhibited the most prominent molecular response among the hippocampus, cerebral cortex, and brainstem vestibular region. Candidate molecules were further screened by integrating network centrality, statistical significance, functional relevance, druggability, and neurological disease correlation. Reverse transcription quantitative real-time PCR and Western blot were performed to detect the expression changes of candidate proteins in brainstem vestibular region tissues of the complete time-series restraint-only control group and habituation group. Temporal validation revealed progressive downregulation of Ywhah and a time-dependent increase in the ratio of phosphorylated Erk1/2 to total Erk1/2 in the vestibular region of the brainstem. The opposite expression trends of Ywhah and p-Erk1/2/total Erk1/2 first reached statistical significance on Day 5, indicating temporal coupling. In summary, this study delineates distinct temporal molecular patterns in the brainstem vestibular region during motion sickness habituation, with overlapping critical time windows for Ywhah suppression and ERK activation. These findings provide reliable longitudinal molecular evidence and promising candidate targets for further exploring the neuroplastic mechanisms of vestibular habituation.
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BibTeX
@article{yue2026timecourse,
title = {{Time-course profiling of behavioral phenotypes and Ywhah/ERK signaling expression within the vestibular region of the brainstem during motion sickness habituation}},
author = {Xue Yue and Chenxi Jia and Lihong Zhai and Jie Deng and Dongjun Yang and Zhanguo Jin},
journal = {Frontiers in Neuroscience},
year = {2026},
month = oct,
doi = {10.3389/fnins.2026.1955920},
url = {https://www.frontiersin.org/articles/10.3389/fnins.2026.1955920/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Time-course profiling of behavioral phenotypes and Ywhah/ERK signaling expression within the vestibular region of the brainstem during motion sickness habituation
AU - Xue Yue
AU - Chenxi Jia
AU - Lihong Zhai
AU - Jie Deng
AU - Dongjun Yang
AU - Zhanguo Jin
PY - 2026
DA - 2026/10/07
JO - Frontiers in Neuroscience
DO - 10.3389/fnins.2026.1955920
UR - https://www.frontiersin.org/articles/10.3389/fnins.2026.1955920/full
AB - Motion sickness habituation represents a core neuroplastic model for investigating vestibular disorder adaptation, yet its brain-region-specific temporal molecular mechanisms remain poorly defined. Here, we adopted multi-brain-region proteomic screening combined with time-series molecular validation to characterize key molecular dynamics during motion sickness habituation. Adult mice received 15 consecutive days of sinusoidal rotational stimulation, and model establishment was verified via four behavioral indices. A self-constructed five-dimensional weighted scoring system based on proteomic data confirmed that the vestibular region of the brainstem exhibited the most prominent molecular response among the hippocampus, cerebral cortex, and brainstem vestibular region. Candidate molecules were further screened by integrating network centrality, statistical significance, functional relevance, druggability, and neurological disease correlation. Reverse transcription quantitative real-time PCR and Western blot were performed to detect the expression changes of candidate proteins in brainstem vestibular region tissues of the complete time-series restraint-only control group and habituation group. Temporal validation revealed progressive downregulation of Ywhah and a time-dependent increase in the ratio of phosphorylated Erk1/2 to total Erk1/2 in the vestibular region of the brainstem. The opposite expression trends of Ywhah and p-Erk1/2/total Erk1/2 first reached statistical significance on Day 5, indicating temporal coupling. In summary, this study delineates distinct temporal molecular patterns in the brainstem vestibular region during motion sickness habituation, with overlapping critical time windows for Ywhah suppression and ERK activation. These findings provide reliable longitudinal molecular evidence and promising candidate targets for further exploring the neuroplastic mechanisms of vestibular habituation.
SN - 1662-453X
SN - 1662-4548
ER -