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.
Highlights
While there is abundant information from experimental studies on the survival requirements of young motor neurons, not much is known about adult and aged motor neurons, and there is reason to think that young motor neurons are inappropriate models for age-related neurodegeneration, such as MND [1]
We consider whether age-related increases in inflammation “inflammaging” [7] can affect facial motor neuron survival, by correlating age-related motoneuronal survival with changes in the central nervous system (CNS) parenchyma in the brainstem at the level of the facial nucleus and in the blood
In contrast to the brainstem region of the CNS, we find that peripheral cytokines show a general decline with aging, which is at odds with initial studies on “inflammaging” by others showing increased levels of individual inflammatory markers in the periphery, especially IL-6 [43,44,45]
Summary
While there is abundant information from experimental studies on the survival requirements of young motor neurons, not much is known about adult and aged motor neurons, and there is reason to think that young motor neurons are inappropriate models for age-related neurodegeneration, such as MND [1]. We consider whether age-related increases in inflammation “inflammaging” [7] can affect facial motor neuron survival, by correlating age-related motoneuronal survival with changes in the central nervous system (CNS) parenchyma in the brainstem at the level of the facial nucleus and in the blood. The link between aging and inflammation has led to the concept of “inflammaging” [10], which is defined as a low-grade chronic inflammatory state associated with the aging process. This concept centers on age-related inflammatory cytokine-driven innate immune responses in the peripheral immune system. Age-related changes in cytokines have been compared with age-related changes in total numbers of facial motor neurons as well as age-related changes in the fiber density of the peripheral target muscle and changes in exploratory behavior
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