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Chronic unpredictable mild stress accelerates lipopolysaccharide- induced microglia activation and damage of

Hua Kong1, Li Yang1, Can He1

  • 1Department of Pharmacology, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, PR China.

Pharmacology, Biochemistry, and Behavior
|January 19, 2019
PubMed

Insights

Chronic unpredictable mild stress (CUMS) worsens Parkinson's disease (PD) in rats by increasing neuroinflammation and activating the NLRP3 inflammasome pathway. This stress model exacerbates microglia activation and dopaminergic neuron damage.

Area of Science:

  • Neuroscience
  • Immunology
  • Pathology

Background:

  • Parkinson's disease (PD) involves microglia activation and neuroinflammation.
  • Inflammation is crucial for PD initiation and progression.
  • The NLRP3 inflammasome complex plays a role in inflammatory responses.

Purpose of the Study:

  • To investigate the effect of chronic unpredictable mild stress (CUMS) on microglia and NLRP3 inflammasome activation in a PD rat model.
  • To determine if CUMS sensitizes microglia to pro-inflammatory stimuli.

Main Methods:

  • In vivo experiments using a rat model of PD.
  • Administration of CUMS for 14 days.
  • Assessment of behavioral dysfunction, microglia activation, inflammatory cytokine levels (IL-1β, IL-6, TNF-α), and NLRP3 inflammasome components (NLRP3, ASC, Caspase-1) in the substantia nigra.

Main Results:

  • CUMS pretreatment aggravated behavioral deficits in PD rats.
  • CUMS increased microglia activation and dopaminergic neuron damage.
  • CUMS elevated serum levels of IL-1β, IL-6, and TNF-α.
  • CUMS upregulated NLRP3, ASC, and Caspase-1 expression in the substantia nigra.

Conclusions:

  • CUMS exacerbates PD-related pathology in rats.
  • The mechanism involves enhanced neuroinflammation and NLRP3 inflammasome activation.
  • Stress may be a significant factor in PD pathogenesis.
Keywords:
InflammationMicrogliaNLRP3Parkinson's diseaseStress

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