Related Experiment Video
Updated: Jan 7, 2026
Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease
Published on: January 7, 2014
Infralimbic Cortex Microglial TREM-1 Mediates Neuroinflammation and Exacerbates Depressive-Like Behaviors in
Yuan-Qing Chu1,2,3, Wei Song1,2,3,4, Zhi-Jing Song1,2,3,5
1NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, 221004, Xuzhou, China.
Abstract:
Depression is a common nonmotor feature of Parkinson's disease (PD) that severely compromises the quality of life of patients, yet its pathogenesis remains elusive. Triggering receptor expressed on myeloid cells 1 (TREM-1) is an immunoglobulin family receptor present on myeloid cells that amplifies neuroinflammatory cascades. However, the contribution of TREM-1 to the depressive-like behaviors associated with PD remains unclear. In a subacute model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) administered at a dose of 30 mg/kg/day for five consecutive days, we evaluated depressive-like behaviors and the expression of microglial TREM-1 in the infralimbic cortex (IL) on Days 3, 7, 14, and 21 following the final MPTP injection. Microglial TREM-1 expression in the IL peaked on Day 14, which coincided with the peak severity of depressive-like behaviors. Both genetic knockout and pharmacological blockade of TREM-1 attenuated proinflammatory cytokines production and reversed depressive-like behaviors. Together, these findings suggested that TREM-1 is a pivotal mediator of microglia-driven neuroinflammation and depression in PD model mice, underscoring its potential as a therapeutic target for nonmotor symptoms.
Insights
Triggering receptor expressed on myeloid cells 1 (TREM-1) drives neuroinflammation and depression in Parkinson's disease models. Blocking TREM-1 reduced depressive behaviors and inflammation, suggesting it as a therapeutic target.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Depression is a common nonmotor symptom in Parkinson's disease (PD), significantly impacting patient quality of life.
- The precise mechanisms underlying PD-related depression remain incompletely understood.
- Triggering receptor expressed on myeloid cells 1 (TREM-1) amplifies neuroinflammatory responses mediated by myeloid cells.
Purpose of the Study:
- To investigate the role of TREM-1 in mediating depressive-like behaviors in a Parkinson's disease mouse model.
- To examine the expression patterns of microglial TREM-1 in relation to depressive symptoms.
Main Methods:
- A subacute mouse model of Parkinson's disease was established using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP).
- Depressive-like behaviors and microglial TREM-1 expression in the infralimbic cortex were assessed at multiple time points post-MPTP administration.
- Genetic knockout and pharmacological blockade of TREM-1 were employed to evaluate their effects on neuroinflammation and behavior.
Main Results:
- Microglial TREM-1 expression in the infralimbic cortex peaked on Day 14, correlating with the highest severity of depressive-like behaviors.
- Both genetic deletion and pharmacological inhibition of TREM-1 significantly reduced the production of proinflammatory cytokines.
- TREM-1 inhibition reversed the observed depressive-like behaviors in the PD model mice.
Conclusions:
- TREM-1 acts as a key mediator in microglia-driven neuroinflammation contributing to depression in Parkinson's disease models.
- Targeting TREM-1 presents a promising therapeutic strategy for addressing nonmotor symptoms, particularly depression, in Parkinson's disease.
More Related Videos
10:40Immunofluorescence Staining Using IBA1 and TMEM119 for Microglial Density, Morphology and Peripheral Myeloid Cell Infiltration Analysis in Mouse Brain
Published on: October 27, 2019
09:12Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
