Effects of intraperitoneal injection of lipopolysaccharide-induced peripheral inflammation on dopamine neuron damage in rat midbrain

CNS Neurosci Ther. 2022 Oct;28(10):1624-1636. doi: 10.1111/cns.13906. Epub 2022 Jul 4.

Abstract

Introduction: Current studies have documented neuroinflammation is implicated in Parkinson's disease. Recently, growing evidence indicated peripheral inflammation plays an important role in regulation of neuroinflammation and thus conferring protection against dopamine (DA) neuronal damage. However, the underlying mechanisms are not clearly illuminated.

Methods: The effects of intraperitoneal injection of LPS (LPS[i.p.] )-induced peripheral inflammation on substantia nigra (SN) injection of LPS (LPS[SN] )-elicited DA neuronal damage in rat midbrain were investigated. Rats were intraperitoneally injected with LPS (0.5 mg/kg) daily for 4 consecutive days and then given single injection of LPS (8 μg) into SN with an interval of 0 (LPS(i.p.) 0 day ± LPS(SN) ), 30 (LPS(i.p.) 30 days ± LPS(SN) ), and 90 (LPS(i.p.) 90 days ± LPS(SN) ) days after LPS(i.p.) administration.

Results: LPS(i.p.) increased the levels of inflammatory factors in peripheral blood in (LPS(i.p.) 0 day ± LPS(SN) ). Importantly, in (LPS(i.p.) 0 day ± LPS(SN) ) and (LPS(i.p.) 30 days ± LPS(SN) ), LPS(i.p.) attenuated LPS(SN) -induced DA neuronal loss in SN. Besides, LPS(i.p.) reduced LPS(SN) -induced microglia and astrocytes activation in SN. Furtherly, LPS(i.p.) reduced pro-inflammatory M1 microglia markers mRNA levels and increased anti-inflammatory M2 microglia markers mRNA levels. In addition, the increased T-cell marker expression and the decreased M1 microglia marker expression and more DA neuronal survival were discerned at the same area of rat midbrain in LPS(SN) -induced DA neuronal damage 30 days after LPS(i.p.) application.

Conclusion: This study suggested LPS(i.p.) -induced peripheral inflammation might cause T cells to infiltrate the brain to regulate microglia-mediated neuroinflammation, thereby protecting DA neurons.

Keywords: Parkinson's disease; dopamine neuron damage; lipopolysaccharide; neuroinflammation; peripheral inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Dopaminergic Neurons*
  • Inflammation / metabolism
  • Injections, Intraperitoneal
  • Lipopolysaccharides* / toxicity
  • Mesencephalon / metabolism
  • Microglia
  • RNA, Messenger / metabolism
  • Rats
  • Substantia Nigra

Substances

  • Biomarkers
  • Lipopolysaccharides
  • RNA, Messenger