Age and duration of inflammatory environment differentially affect the neuroimmune response and catecholaminergic neurons in the midbrain and brainstem

Isabelle Bardou, Roxanne M. Kaercher, Holly M. Brothers, Sarah C Hopp, Sarah Royer, Gary L. Wenk

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Neuroinflammation and degeneration of ascending catecholaminergic systems occur early in the neurodegenerative process. Age and the duration of a pro-inflammatory environment induced by continuous intraventricular lipopolysaccharide (LPS) differentially affect the expression profile of pro- and anti-inflammatory genes and proteins as well as the number of activated microglia (express major histocompatibility complex II; MHC II) and the integrity and density of ascending catecholaminergic neural systems originating from the locus coeruleus (LC) and substantia nigra pars compacta (SNpc) in rats. LPS infusion increased gene expression and/or protein levels for both pro- and anti-inflammatory biomarkers. Although LPS infusion stimulated a robust increase in IL-1ß gene and protein expression, this increase was blunted with age. LPS infusion also increased the density of activated microglia cells throughout the midbrain and brainstem. Corresponding to the development of a pro-inflammatory environment, LC and SNpc neurons immunopositive for tyrosine-hydroxylase (the rate-limiting synthetic enzyme for dopamine and norepinephrine) decreased in number, along with a decrease in tyrosine-hydroxylase gene expression in the midbrain and/or brainstem region. Our data support the concept that continuous exposure to a pro-inflammatory environment drives exaggerated changes in the production and release of inflammatory mediators that interact with age to impair functional capacity of the SNpc and LC.

Original languageEnglish (US)
Pages (from-to)1065-1073
Number of pages9
JournalNeurobiology of Aging
Volume35
Issue number5
DOIs
StatePublished - May 1 2014
Externally publishedYes

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Mesencephalon
Brain Stem
Locus Coeruleus
Lipopolysaccharides
Neurons
Tyrosine 3-Monooxygenase
Microglia
Gene Expression
Anti-Inflammatory Agents
Proteins
Major Histocompatibility Complex
Interleukin-1
Dopamine
Norepinephrine
Biomarkers
Enzymes
Pars Compacta

Keywords

  • Aging
  • Alzheimer's disease
  • Cytokines
  • Locus coeruleus
  • Microglia
  • Neuroinflammation
  • Parkinson's disease
  • Rat
  • Substantia nigra

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

Age and duration of inflammatory environment differentially affect the neuroimmune response and catecholaminergic neurons in the midbrain and brainstem. / Bardou, Isabelle; Kaercher, Roxanne M.; Brothers, Holly M.; Hopp, Sarah C; Royer, Sarah; Wenk, Gary L.

In: Neurobiology of Aging, Vol. 35, No. 5, 01.05.2014, p. 1065-1073.

Research output: Contribution to journalArticle

Bardou, Isabelle ; Kaercher, Roxanne M. ; Brothers, Holly M. ; Hopp, Sarah C ; Royer, Sarah ; Wenk, Gary L. / Age and duration of inflammatory environment differentially affect the neuroimmune response and catecholaminergic neurons in the midbrain and brainstem. In: Neurobiology of Aging. 2014 ; Vol. 35, No. 5. pp. 1065-1073.
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