Cellular and Subcellular Evidence for Neuronal Interaction between the Chemokine Stromal Cell-Derived Factor-1/CXCL 12 and Vasopressin: Regulation in the Hypothalamo-Neurohypophysial System of the Brattleboro Rats

Abstract

We previously described a colocalization between arginine vasopressin (AVP) and the chemokine stromal cell-derived factor-1alpha (SDF-1) in the magnocellular neurons of both the hypothalamic supraoptic and paraventricular nucleus as well as the posterior pituitary. SDF-1 physiologically affects the electrophysiological properties of AVP neurons and consequently AVP release. In the present study, we confirm by confocal and electron microscopy that AVP and SDF-1 have a similar cellular distribution inside the neuronal cell and can be found in dense core vesicles in the nerve terminals in the posterior pituitary. Because the Brattleboro rats represent a good model of AVP deficiency, we tested in these animals the fate of SDF-1 and its receptor CXCR4. We identified by immunohistochemistry that both SDF-1 and CXCR4 immunoreactivity were strongly decreased in Brattleboro rats and were strictly correlated with the expression of AVP protein in supraoptic nucleus, paraventricular nucleus, and the posterior pituitary. We observed by real-time PCR an increase in SDF-1 mRNA in both heterozygous and homozygous rats. The effect on the SDF-1/CXCR4 system was not linked to peripheral modifications of kidney water balance because it could not be restored by chronic infusion of deamino-8D-ariginine-vasopressin, an AVP V2-receptor agonist. These original data further suggest that SDF-1 may play an essential role in the regulation of water balance.

SDF-1α/CXCL12 enhances GABA and glutamate synaptic activity at serotonin neurons in the rat dorsal raphe nucleus

“…Immunohistochemical analysis of CXCL12 and CXCR4 labeling in the RN by confocal microscopy indicates that these immune proteins are expressed as discrete puncta in the cytoplasm and outer membrane of 5-HT cell bodies and processes. The punctate staining pattern has been observed for CXCL12 and CXCR4 in previous immunohistochemistry studies in various brain regions (Banisadr et al, 2002; Banisadr et al, 2003; Rostasy et al, 2003; Miller et al, 2005; Callewaere et al, 2008; McCandless et al, 2008) including the DRN (Banisadr et al, 2002; Banisadr et al, 2003; Callewaere et al, 2008) as well as in the periphery (Hu et al, 2007). …”

“…In previous electron microscopy studies of the rat posterior pituitary, vasopressinergic neurons were shown to contain CXCL12 in dense-core vesicles (Callewaere et al, 2008). Furthermore, although cellular processes were not stained for specific axonal or dendritic markers, the localization of CXCR4 in the outer membrane and processes of 5-HT neurons suggests that CXCL12’s interactions with CXCR4 may have a role in 5-HT mediated synaptic transmission (Limatola et al, 2000).…”

Implication of CCR2 Chemokine Receptor in Cocaine-Induced Sensitization

“…In the central nervous system (CNS), chemokines are detected in glial cells and neurons (Miller et al 2008). Chemokines can act as neuromodulators through their receptors in the healthy CNS, namely in spinal cord (Gosselin et al 2005), hypothalamus (Callewaere et al 2008) and the nigrostriatal pathway (Skrzydelski et al 2007). We recently observed that the chemokine CCL2 enhances striatal DA release and locomotion (Guyon et al 2009).…”

Effect of Cadmium Contaminated Diet in Controlling Water Behavior by Meriones shawi

“…We hypothesized that potential effects of Cd might include exaggerated synthesis of AVP during Cd exposure in our model Meriones shawi and support the idea of an increase of AVP as result of Cd intoxication (see figure 2 and 3). These findings suggest that Cd ingestion has potential effects on the vasopressinergic system that responds with elevated synthesis of AVP under stimulated conditions [57]. A large number of studies have demonstrated that Cd exposure produce marked neuroendocrine changes in animals [58][59] and human [60].…”