PUBLICATION
Sleep Deprivation-Induced TLR4/MyD88/NF-κB Pathway Dysregulation Worsens Cognitive Impairment In Parkinson's Disease
- Authors
- Liu, T., Zhang, Y., Li, X., Liu, S., Zhu, X., Ren, Y., Han, R., Liu, K., Sun, C., Li, X., Ji, X.
- ID
- ZDB-PUB-260124-14
- Date
- 2026
- Source
- Behavioural brain research : 116058116058 (Journal)
- Registered Authors
- Keywords
- Apoptosis, Autophagy, Cognitive impairment, Parkinson’s disease, Sleep deprivation, TLR4
- MeSH Terms
-
- Animals
- Apoptosis
- Cognitive Dysfunction*/etiology
- Cognitive Dysfunction*/metabolism
- Cognitive Dysfunction*/physiopathology
- Disease Models, Animal
- Male
- Myeloid Differentiation Factor 88*/metabolism
- NF-kappa B*/metabolism
- Parkinson Disease*/complications
- Parkinson Disease*/metabolism
- Parkinsonian Disorders*/complications
- Parkinsonian Disorders*/metabolism
- Signal Transduction/physiology
- Sleep Deprivation*/complications
- Sleep Deprivation*/metabolism
- Sleep Deprivation*/physiopathology
- Toll-Like Receptor 4*/metabolism
- Zebrafish
- PubMed
- 41577012 Full text @ Behav. Brain Res.
Citation
Liu, T., Zhang, Y., Li, X., Liu, S., Zhu, X., Ren, Y., Han, R., Liu, K., Sun, C., Li, X., Ji, X. (2026) Sleep Deprivation-Induced TLR4/MyD88/NF-κB Pathway Dysregulation Worsens Cognitive Impairment In Parkinson's Disease. Behavioural brain research. :116058116058.
Abstract
Parkinson's disease (PD) is a common neurodegenerative disorder. It has motor symptoms and non motor symptoms, like cognitive impairment, sleep disturbance. = Studies show PD patient with sleep disorders show more severe cognitive impairment. To investigate the underlying mechanisms, we used a PD zebrafish model induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and simulated insomnia by sleep deprivation (SD). Behavioral tests showed that SD exacerbated cognitive impairment. SD aggravated vascular loss and dopaminergic neuron damage. RT-qPCR analysis revealed the highest expression levels of Toll Like Receptor 4 (tlr-4), Myeloid Differentiation Primary Response 88 (myd88), Nuclear Factor Kappa B (nfκb), Caspase 3 (casp3), BCL2 Associated X, Apoptosis Regulator (bax) in the SD co-treatment group, indicating maximal Toll Like Receptor 4 (TLR4)/Myeloid Differentiation Primary Response 88 (MyD88)/Nuclear Factor Kappa B (NF-κB) pathway activation and apoptosis levels, while Autophagy Related 5 (atg5) expression was lowest, indicating severe autophagy dysfunction. ELISA detected the highest levels of IL-6 and TNF-α, indicating maximal neuroinflammation. This study clarified the mechanism of SD exacerbating PD cognitive impairment: SD upregulates the TLR4/MyD88/NF-κB pathway, which intensifies neuroinflammation and apoptosis and led to autophagy dysfunction. This study revealed the potential mechanism between sleep disturbance and cognitive impairment in PD patients, provided a theoretical basis for the therapies targeting the TLR4/MyD88/NF-κB pathway, holds significant clinical significance for enhancing the quality of life of PD patients.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping