Distribution of preproadrenomedullin mRNA in the rat central nervous system and its modulation by physiological stressors

Adrenomedullin (ADM), encoded by the preproadrenomedullin (ppADM) gene, exerts multiple effects in a wide variety of peripheral and central tissues. Although ADM-like immunoreactivity has been shown to be widely distributed throughout the rat central nervous system (CNS), the detailed distribution of ppADM gene expression in the CNS and its modulation by physiological stimuli remain unknown. In our study, in situ hybridization was used to localize ppADM mRNA in the rat brain and to quantify its levels after exposure to different stressors including lipopolysaccharide (LPS; 100 microg/kg, iv), restraint stress (2 cycles of 1 hour restraint/1 hour rest), and 24 hours of dehydration. In addition, Fos immunoreactivity was used to identify the activation of neurons in response to LPS. Our results show that ppADM mRNA is widely distributed throughout the rat CNS, with especially high levels in autonomic centers including the hypothalamic paraventricular nucleus (PVN), hypothalamic supraoptic nucleus (SON), locus coeruleus, ventrolateral medulla, and intermediolateral cell column of the spinal cord. Furthermore, LPS inhibits ppADM gene expression in the parvocellular PVN (pPVN), magnocellular PVN (mPVN), SON, dorsal motor nucleus of the vagus, and area postrema among examined regions; restraint stress reduces ppADM mRNA levels in the pPVN, mPVN, SON, nucleus of the solitary tract, dorsal motor nucleus of the vagus, area postrema, and subfornical organ; 24 hours of water deprivation decreases ppADM gene expression only in the mPVN and SON. Taken together, our results suggest that ADM is involved in the regulation of the hypothalamo-neurohypophysial system, the hypothalamo-pituitary-adrenal axis, and central autonomic functions.