Circadian disruption exacerbates cognitive impairment via an intense neuroinflammatory reaction and alpha-synuclein deposition in a Parkinson's disease mouse model.
Rong Deng, Chang Liu, Hong Jin, Yulan Cao, Lanxiang Wang, Yuting Zhang, Fen Wang, Jing Chen
{"title":"Circadian disruption exacerbates cognitive impairment via an intense neuroinflammatory reaction and alpha-synuclein deposition in a Parkinson's disease mouse model.","authors":"Rong Deng, Chang Liu, Hong Jin, Yulan Cao, Lanxiang Wang, Yuting Zhang, Fen Wang, Jing Chen","doi":"10.1097/WNR.0000000000002182","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is a chronic neurodegenerative disorder marked by motor symptoms and nonmotor complications, notably cognitive impairment, which severely impairs patients' quality of life. While circadian disruption (CD) correlates with cognitive decline in PD, it remains unclear whether CD is merely secondary to motor symptoms or directly contributes to cognitive dysfunction. The objective of this study was to investigate whether chronic CD exacerbates cognitive decline in PD.</p><p><strong>Basic methods: </strong>Male mice were subjected to the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD and divided into groups with or without chronic exposure to CD. Observational assessments of cognitive deficits were performed alongside analytical measurements of tyrosine hydroxylase (TH) content in the striatum, α-synuclein deposition levels, and neuroinflammatory responses in the hippocampus.</p><p><strong>Main results: </strong>MPTP-treated mice exposed to CD exhibited significantly more severe cognitive deficits compared to MPTP-treated controls without CD. These deficits correlated with pronounced reductions in striatal TH content, elevated α-synuclein accumulation, and intensified neuroinflammatory activity in the hippocampal region. The observed changes demonstrated CD-induced exacerbation of pathological hallmarks.</p><p><strong>Conclusions: </strong>Chronic CD directly aggravates MPTP-driven neuroinflammatory processes and α-synuclein pathology in the hippocampus, leading to accelerated cognitive deterioration. These findings substantiate CD as an environmental risk factor for cognitive decline in PD progression, independent of motor symptom sequelae. The study provides mechanistic insights into CD's contributory role in PD-related cognitive impairment.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":""},"PeriodicalIF":1.6000,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuroreport","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/WNR.0000000000002182","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Parkinson's disease (PD) is a chronic neurodegenerative disorder marked by motor symptoms and nonmotor complications, notably cognitive impairment, which severely impairs patients' quality of life. While circadian disruption (CD) correlates with cognitive decline in PD, it remains unclear whether CD is merely secondary to motor symptoms or directly contributes to cognitive dysfunction. The objective of this study was to investigate whether chronic CD exacerbates cognitive decline in PD.
Basic methods: Male mice were subjected to the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD and divided into groups with or without chronic exposure to CD. Observational assessments of cognitive deficits were performed alongside analytical measurements of tyrosine hydroxylase (TH) content in the striatum, α-synuclein deposition levels, and neuroinflammatory responses in the hippocampus.
Main results: MPTP-treated mice exposed to CD exhibited significantly more severe cognitive deficits compared to MPTP-treated controls without CD. These deficits correlated with pronounced reductions in striatal TH content, elevated α-synuclein accumulation, and intensified neuroinflammatory activity in the hippocampal region. The observed changes demonstrated CD-induced exacerbation of pathological hallmarks.
Conclusions: Chronic CD directly aggravates MPTP-driven neuroinflammatory processes and α-synuclein pathology in the hippocampus, leading to accelerated cognitive deterioration. These findings substantiate CD as an environmental risk factor for cognitive decline in PD progression, independent of motor symptom sequelae. The study provides mechanistic insights into CD's contributory role in PD-related cognitive impairment.
期刊介绍：
NeuroReport is a channel for rapid communication of new findings in neuroscience. It is a forum for the publication of short but complete reports of important studies that require very fast publication. Papers are accepted on the basis of the novelty of their finding, on their significance for neuroscience and on a clear need for rapid publication. Preliminary communications are not suitable for the Journal. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool.
The core interest of the Journal is on studies that cast light on how the brain (and the whole of the nervous system) works.
We aim to give authors a decision on their submission within 2-5 weeks, and all accepted articles appear in the next issue to press.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
