title: Disparate Changes in Plasma and Brainstem Cytokine Levels in Adult and Ageing Rats Associated with Age-Related Changes in Facial Motor Neuron Number, Snout Muscle Morphology, and Exploratory Behavior.
abstract: An overall increase in inflammatory cytokines with age in both the blood and the central nervous system (CNS) has been proposed to explain many aspects of ageing, including decreased motor function and neurodegeneration. This study tests the hypothesis that age-related increases in inflammatory cytokines in the blood and CNS lead to facial motor neuron degeneration. Groups of 3-5 female Sprague-Dawley rats aged 3, 12-18, and 24 months were used. Twelve cytokines interleukin (IL)-1α, IL-β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, tumor necrosis factor-α (TNFα), interferon-γ, and granulocyte macrophage-colony stimulating factor were measured in blood plasma and compared with those in the brainstem after first flushing blood from its vessels. The open-field test was used to measure exploratory behavior, and the morphology of the peripheral target muscle of facial motor neurons quantified. Total numbers of facial motor neurons were determined stereologically in separate groups of 3- and 24-month-old rats. Ageing rats showed a significant 30-42% decrease in blood plasma (peripheral) concentrations of IL-12p70 and TNFα and a significant 43-49% increase in brainstem (central) concentrations of IL-1α, IL-2, IL-4, IL-10, and TNFα. They also showed significant reductions in motor neuron number in the right but not left facial nucleus, reduced exploratory behavior, and increase in peripheral target muscle size. Marginal age-related facial motoneuronal loss occurs in the ageing rat and is characterized by complex changes in the inflammatory signature, rather than a general increase in inflammatory cytokines.
authors.affiliation: Anatomy and Pathology, The University of Adelaide , Adelaide, SA , Australia.
authors.forename: Viythia
authors.initials: V
authors.lastname: Katharesan
authors.affiliation: Mind and Brain Theme, South Australian Health and Medical Research Institute , Adelaide, SA , Australia.
authors.forename: Martin David
authors.initials: MD
authors.lastname: Lewis
authors.affiliation: Health Sciences Divisional Office, University of South Australia , Adelaide, SA , Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: Vink
authors.affiliation: Anatomy and Pathology, The University of Adelaide , Adelaide, SA , Australia.
authors.forename: Ian Paul
authors.initials: IP
authors.lastname: Johnson
keywords: ageing; cytokines; inflammaging; motor neurons; neurodegeneration; rat