title: Age and duration of inflammatory environment differentially affect the neuroimmune response and catecholaminergic neurons in the midbrain and brainstem.
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.
authors: Department of Psychology, The Ohio State University, Columbus, OH, USA; Department of Neuroscience, The Ohio State University, Columbus, OH, USA.
authors: Isabelle
authors: I
authors: Bardou
authors: Department of Psychology, The Ohio State University, Columbus, OH, USA; Department of Neuroscience, The Ohio State University, Columbus, OH, USA.
authors: Roxanne M
authors: RM
authors: Kaercher
authors: Department of Psychology, The Ohio State University, Columbus, OH, USA; Department of Neuroscience, The Ohio State University, Columbus, OH, USA.
authors: Holly M
authors: HM
authors: Brothers
authors: Department of Psychology, The Ohio State University, Columbus, OH, USA; Department of Neuroscience, The Ohio State University, Columbus, OH, USA.
authors: Sarah C
authors: SC
authors: Hopp
authors: Department of Psychology, The Ohio State University, Columbus, OH, USA; Department of Neuroscience, The Ohio State University, Columbus, OH, USA.
authors: Sarah
authors: S
authors: Royer
authors: Department of Psychology, The Ohio State University, Columbus, OH, USA; Department of Neuroscience, The Ohio State University, Columbus, OH, USA. Electronic address: wenk.6@osu.edu.
authors: Gary L
authors: GL
authors: Wenk
mesh_terms: D000375:Aging / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D000818:Animals; D002395:Catecholamines / Q000502:physiology*; D015870:Gene Expression; D007249:Inflammation / Q000235:genetics* / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008125:Locus Coeruleus / Q000276:immunology* / Q000473:pathology*; D008297:Male; D017628:Microglia / Q000276:immunology / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000276:immunology / Q000473:pathology; D015213:Neuroimmunomodulation / Q000235:genetics*; D009474:Neurons / Q000276:immunology* / Q000473:pathology*; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000276:immunology* / Q000473:pathology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000276:immunology
chemical_list: D002395:Catecholamines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D010446:Peptide Fragments; C052994:interleukin-1beta (163-171); D014446:Tyrosine 3-Monooxygenase
keywords: Aging; Alzheimer's disease; Cytokines; Locus coeruleus; Microglia; Neuroinflammation; Parkinson's disease; Rat; Substantia nigra