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

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.

Extrasynaptic localization of glycine receptors in the rat supraoptic nucleus: further evidence for their involvement in glia-to-neuron communication.

Neurons of the rat supraoptic nucleus (SON) express glycine receptors (GlyRs), which are implicated in the osmoregulation of neuronal activity. The endogenous agonist of the receptors has been postulated to be taurine, shown to be released from astrocytes. We here provide additional pieces of evidence supporting the absence of functional glycinergic synapses in the SON. First, we show that blockade of GlyRs with strychnine has no effect on either the amplitude or frequency of miniature inhibitory postsynaptic currents recorded in SON neurons, whereas they were all suppressed by the GABA(A) antagonist gabazine. Then, double immunostaining of sections with presynaptic markers and either GlyR or GABA(A) receptor (GABA(A)R) antibodies indicates that, in contrast with GABA(A)Rs, most GlyR membrane clusters are not localized facing presynaptic terminals, indicative of their extrasynaptic localization. Moreover, we found a striking anatomical association between SON GlyR clusters and glial fibrillary acidic protein (GFAP)-positive astroglial processes, which contain high levels of taurine. This type of correlation is specific to GlyRs, since GABA(A)R clusters show no association with GFAP-positive structures. These results substantiate and strengthen the concept of extrasynaptic GlyRs mediating a paracrine communication between astrocytes and neurons in the SON.