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Neurobiol Aging. 2009 Oct;30(10):1677-92. doi: 10.1016/j.neurobiolaging.2007.12.006. Epub 2008 Feb 5.

Age-impaired fluid homeostasis depends on the balance of IL-6/IGF-I in the rat supraoptic nuclei.

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Laboratoire PsyNuGen, CNRS UMR5226, Université de Bordeaux, INRA UMR1286, IFR8 Neurosciences, UFR de Pharmacie, 146 rue Léo Saignat, Bordeaux F-33077, France.


Adaptive metabolic changes associated with bacterial infections are likely to cause dehydration. Activation of hypothalamic neurons in the supraoptic nucleus that release anti-diuretic arginine-vasopressin in plasma provides water retention. Aging is characterized by arginine-vasopressin neuron hyper-activity and over-expression of pro-inflammatory cytokines like interleukin (IL)-6. Conversely, insulin-like growth factor (IGF)-I, known to exhibit anti-inflammatory properties, decreases with age. We compared activation of arginine-vasopressin neurons in adult (3 months) and aged (22 months) Wistar rats by measuring not only c-fos expression, plasma arginine-vasopressin and diuresis but also the expression of IL-6 and IGF-I in the supraoptic nuclei after intraperitoneal lipopolysaccharide injection. Aged rats displayed a heightened, shorter lasting activation of arginine-vasopressin neurons following lipopolysaccharide as compared to adults. IL-6 mRNA was 3-fold higher while IGF-I mRNA was 10-fold lower in aged than in adult rats. Brain pre-treatment with neutralizing anti-IL-6 antibodies or recombinant IGF-I in aged rats reversed lipopolysaccharide-induced anti-diuresis. These data extend the concept of neuroendocrine-immune interactions to the arginine-vasopressin neuronal system by establishing a relationship between brain IL-6/IGF-I balance and age-associated arginine-vasopressin neuronal dysfunction.

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