Restraint stress activates nesfatin-1-immunoreactive brain nuclei in rats.

Nesfatin-1 is a newly discovered peptide that was reported to reduce food intake when injected centrally. We recently described its wide distribution in rat brain autonomic nuclei which implies potential recruitment of nesfatin-1 by stress. We investigated whether restraint, a mixed psychological and physical stressor, activates nesfatin-1-immunoreactive (ir) neurons in the rat brain. Male Sprague-Dawley rats were either subjected to 30 min restraint or left undisturbed and 90 min later brains were processed for double immunohistochemical labeling of Fos and nesfatin-1. Restraint induced significant Fos expression in neurons of the supraoptic nucleus (SON), paraventricular nucleus (PVN), locus coeruleus (LC), rostral raphe pallidus (rRPa), nucleus of the solitary tract (NTS), and ventrolateral medulla (VLM). Double Fos/nesfatin-1 labeling revealed that Fos-ir neurons comprised 95% of nesfatin-1-ir cells in the SON, 90% in the VLM, 80% in the LC, 48% in the caudal NTS, 57% in the rRPa, 48% in the anterior parvicellular PVN, 27% in the medial magnocellular PVN, 18% in the lateral magnocellular PVN and 10% in the medial parvicellular PVN. These data demonstrate that nesfatin-1 neurons are part of the hypothalamic and hindbrain neuronal cell groups activated by restraint suggesting a possible role of nesfatin-1 in the response to stress.