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 language | English (US) |
|---|---|
| Pages (from-to) | 1065-1073 |
| Number of pages | 9 |
| Journal | Neurobiology of Aging |
| Volume | 35 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 1 2014 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Age and duration of inflammatory environment differentially affect the neuroimmune response and catecholaminergic neurons in the midbrain and brainstem
AU - Bardou, Isabelle
AU - Kaercher, Roxanne M.
AU - Brothers, Holly M.
AU - Hopp, Sarah C
AU - Royer, Sarah
AU - Wenk, Gary L.
PY - 2014/5/1
Y1 - 2014/5/1
N2 - 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.
AB - 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.
KW - Aging
KW - Alzheimer's disease
KW - Cytokines
KW - Locus coeruleus
KW - Microglia
KW - Neuroinflammation
KW - Parkinson's disease
KW - Rat
KW - Substantia nigra
UR - http://www.scopus.com/inward/record.url?scp=84893719111&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84893719111&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2013.11.006
DO - 10.1016/j.neurobiolaging.2013.11.006
M3 - Article
VL - 35
SP - 1065
EP - 1073
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
IS - 5
ER -