Advertisement

Centrally administered bombesin activates COX-containing spinally projecting neurons of the PVN in anesthetized rats

      Abstract

      The paraventricular nucleus (PVN) of the hypothalamus has a heterogenous structure containing different types of output neurons that project to the median eminence, posterior pituitary, brain stem autonomic centers and sympathetic preganglionic neurons in the spinal cord. Presympathetic neurons in the PVN send mono- and poly-synaptic projections to the spinal cord. In the present study using urethane-anesthetized rats, we examined the effects of centrally administered bombesin (a homologue of the mammalian gastrin-releasing peptide) on the mono-synaptic spinally projecting PVN neurons pre-labeled with a retrograde tracer Fluoro-Gold (FG) injected into T8 level of the spinal cord, with regard to the immunoreactivity for cyclooxygenase (COX) isozymes (COX-1/COX-2) and Fos (a marker of neuronal activation). FG-labeled spinally projecting neurons were abundantly observed in the dorsal cap, ventral part and posterior part of the PVN. The immunoreactivity of each COX-1 and COX-2 was detected in FG-labeled spinally projecting PVN neurons in the vehicle (10 μl of saline/animal, i.c.v.)-treated group, while bombesin (1 nmol/animal, i.c.v.) had no effect on the number of these immunoreactive neurons for each COX isozyme with labeling of FG. On the other hand, the peptide significantly increased the number of double-immunoreactive neurons for Fos and COX-1/COX-2 with FG-labeling in the PVN (except triple-labeled neurons for FG, COX-2 and Fos in the dorsal cap of the PVN), as compared to those of vehicle-treated group. These results suggest that centrally administered bombesin activates spinally projecting PVN neurons containing COX-1 and COX-2 in rats.

      Abbreviations:

      ANOVA (analysis of variance), COX (cyclooxygenase), FG (Fluolo-Gold), i.c.v. (intracerebroventricularly), IML (intermediolateral cell column), PVN (hypothalamic paraventricular nucleus)

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Autonomic Neuroscience: Basic and Clinical
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Barron B.A.
        • Van Loon G.R.
        Role of sympathoadrenomedullary system in cardiovascular response to stress in rats.
        J. Auton. Nerv. Syst. 1989; 28: 179-187
        • Bartolomucci A.
        • Palanza P.
        • Costoli T.
        • Savani E.
        • Laviola G.
        • Parmigiani S.
        • Sgoifo A.
        Chronic psychosocial stress persistently alters autonomic function and physical activity in mice.
        Physiol. Behav. 2003; 80: 57-67
        • Birder L.A.
        • de Goat W.C.
        Increase c-fos expression in spinal neurons after irritation of the lower urinary tract in the rat.
        J. Neurosci. 1992; 12: 4878-4889
        • Birder L.A.
        • Roppolo J.R.
        • Erickson V.L.
        • de Groat W.C.
        Increased c-fos expression in spinal lumbosacral projection neurons and preganglionic neurons after irritation of the lower urinary tract in the rat.
        Brain Res. 1999; 834: 55-65
        • Breder C.D.
        • Smith W.D.
        • Raz A.
        • Masferrer J.
        • Seibert K.
        • Needleman P.
        • Saper C.B.
        Distribution and characterization of cyclooxygenase immunoreactivity in the ovine brain.
        J. Comp. Neurol. 1992; 322: 409-438
        • Breder C.D.
        • Dewitt D.
        • Kraig R.P.
        Characterization of inducible cyclooxygenase in rat brain.
        J. Comp. Neurol. 1995; 355: 296-315
        • Burke S.L.
        • Malpas S.C.
        • Head G.A.
        Effects of rilmenidine on the cardiovascular responses to stress in the conscious rabbit.
        Brain Res. 1998; 1059: 197-202
        • Carver-Moore K.
        • Gray T.S.
        • Brown M.R.
        Central nervous system site of action of bombesin to elevate plasma concentrations of catecholamines.
        Brain Res. 1991; 541: 225-231
        • Cham J.L.
        • Klein R.
        • Owens N.C.
        • Mathai M.
        • McKinley M.
        • Badoer E.
        Activation of spinally projecting and nitrergic neurons in the PVN following heat exposure.
        Am. J. Physiol. Regul. Integr. Comp. Physiol. 2006; 291: R91-R101
        • Chung D.W.
        • Yoo K.
        • Hwang I.K.
        • Kim D.W.
        • Chung J.Y.
        • Lee C.H.
        • Choi J.H.
        • Choi S.Y.
        • Youn H.Y.
        • Lee I.S.
        • Won M.
        Systemic administration of lipopolysaccharide induced cyclooxygenase-2 immunoreactivity in endothelium and increases microglia in the mouse hippocampaus.
        Cell. Mol. Neurobiol. 2010; 30: 531-541
        • Corral R.S.
        • Iñiguez M.A.
        • Duque J.
        • López-Pérez R.
        • Fresno M.
        Bombesin induces cyclooxygenase-2 expression through the activation of the nuclear factor of activated T cells and enhances cell migration in Caco-2 colon carcinoma cells.
        Oncogene. 2007; 26: 958-969
        • Cullinan W.E.
        • Herman J.P.
        • Battaglia D.F.
        • Akil H.
        • Watson S.J.
        Pattern and time course of immediate early gene expression in rat brain following acute stress.
        Neuroscience. 1995; 64: 477-505
        • De Boer S.F.
        • Koopmans S.J.
        • Slangen J.L.
        • Van der Gugten J.
        Plasma catecholamine, corticosterone and glucose responses to repeated stress in rats: effects of interstressor interval length.
        Physiol. Behav. 1990; 47: 1117-1124
        • Dronjak S.
        • Gavrilović L.
        • Filipović D.
        • Radojčić M.B.
        Immobilization and cold stress affect sympatho-adrenomedullary system and pituitary-adrenocortical axis of rats exposed to long-term isolation and crowding.
        Physiol. Behav. 2004; 81: 409-415
        • Fujino Y.
        • Fujii T.
        Insulin-induced hypoglycemia stimulates both adrenaline and noradrenaline release from adrenal medulla in 21-day-old rats.
        Jpn. J. Pharmacol. 1995; 69: 413-420
        • Gunion M.W.
        • Taché Y.
        Bombesin microinjection into the paraventricular nucleus suppresses gastric acid secretion in the rat.
        Brain Res. 1987; 411: 156-161
        • Guo Y.S.
        • Hellmich M.R.
        • Wen X.D.
        • Townsend Jr., C.M.
        Activator protein-1 transcription factor mediates bombesin-stimulated cyclooxygenase-2 expression in intestinal epithelial cells.
        J. Biol. Chem. 2001; 276: 22941-22947
        • Hardy S.G.
        Hypothalamic projections to cardiovascular centers of the medulla.
        Brain Res. 2001; 894: 233-240
        • Hayward L.F.
        • Castellanos M.
        Increased c-Fos expression in select lateral parabrachial subnuclei following chemical versus electrical stimulation of the dorsal periaqueductal gray in rats.
        Brain Res. 2003; 974: 153-166
        • Herrera D.G.
        • Robertson H.A.
        Activation of c-fos in the brain.
        Prog. Neurobiol. 1996; 50: 83-107
        • Hétu P.O.
        • Riendeau D.
        Cyclo-oxygenase-2 contributes to constitutive prostanoid production in rat kidney and brain.
        Biochem. J. 2005; 391: 561-566
        • Honkaniemi J.
        • Kononen J.
        • Kainu T.
        • Pyykönen I.
        • Pelto-Huikko M.
        Induction of multiple immediate early genes in rat hypothalamic paraventricular nucleus after stress.
        Brain Res. Mol. Brain Res. 1994; 25: 234-241
        • Imaki T.
        • Shibasaki T.
        • Chikada N.
        • Harada S.
        • Naruse M.
        • Demura H.
        Different expression of immediate-early genes in the rat paraventricular nucleus induced by stress: relation to corticotropin-releasing factor gene transcription.
        Endocr. J. 1996; 43: 629-638
        • Imaki T.
        • Naruse M.
        • Harada S.
        • Chikada N.
        • Nakajima K.
        • Yoshimoto T.
        • Demura H.
        Stress-induced changes of gene expression in the paraventricular nucleus are enhanced in spontaneously hypertensive rats.
        J. Neuroendocrinol. 1998; 10: 635-643
        • Jansen A.S.
        • Nguyen X.V.
        • Karpitskiy V.
        • Mettenleiter T.C.
        • Loewy A.D.
        Central command neurons of the sympathetic nervous system: basis of the fight-or-flight response.
        Science. 1995; 270: 644-646
        • Krukoff T.L.
        • Morton T.L.
        • Harris K.H.
        • Jhamandas J.H.
        Expression of c-fos protein in rat brain elicited by electrical stimulation of the pontine parabrachial nucleus.
        J. Neurosci. 1992; 12: 3582-3590
        • Lu L.
        • Shimizu T.
        • Nakamura K.
        • Yokotani K.
        Brain neuronal/inducible nitric oxide synthases and cyclooxygenase-1 are involved in the bombesin-induced activation of central adrenomedullary outflow in rats.
        Eur. J. Pharmacol. 2008; 590: 177-184
        • Mayorov D.N.
        • Head G.A.
        AT1 receptors in the RVLM mediate pressor responses to emotional stress in rabbits.
        Hypertension. 2003; 41: 1168-1173
        • Motawei K.
        • Pyner S.
        • Ranson R.N.
        • Kamel M.
        • Coote J.H.
        Terminals of paraventricular spinal neurones are closely associated with adrenal medullary sympathetic preganglionic neurones: immunohistochemical evidence for vasopressin as a possible neurotransmitter in this pathway.
        Exp. Brain Res. 1999; 126: 68-76
        • Okada S.
        • Murakami Y.
        • Yokotani K.
        Role of brain thromboxane A2 in the release of noradrenaline and adrenaline from adrenal medulla in rats.
        Eur. J. Pharmacol. 2003; 467: 125-131
        • Okuma Y.
        • Yokotani K.
        • Osumi Y.
        Brain prostaglandins mediate the bombesin-induced increase in plasma levels of catechaolamines.
        Life Sci. 1996; 59: 1217-1225
        • Paxinos G.
        • Watson C.
        The Rat Brain in Stereotaxic Coordinates.
        4th ed. Academic Press, 1998
        • Pyner S.
        Neurochemistry of the paraventricular nucleus of the hypothalamus: Implications for cardiovascular regulation.
        J. Chem. Neuroanat. 2009; 38: 197-208
        • Pyner S.
        • Coote J.H.
        Evidence that sympathetic preganglionic neurones are arranged in target-specific columns in the thoracic spinal cord of the rat.
        J. Comp. Neurol. 1994; 342: 15-22
        • Pyner S.
        • Coote J.H.
        Identification of branching paraventricular neurons of the hypothalamus that project to the rostroventrolateral medulla and spinal cord.
        Neuroscience. 2000; 100: 549-556
        • Ranson R.N.
        • Motawei K.
        • Pyner S.
        • Coote J.H.
        The paraventricular nucleus of the hypothalamus sends efferents of the spinal cord of the rat that closely appose sympathetic preganglionic neurons projecting to the stellate ganglion.
        Exp. Brain Res. 1998; 120: 164-172
        • Rocha M.J.A.
        • Herbert H.
        Effects of anesthetics on Fos protein expression in autonomic brain nuclei related to cardiovascular regulation.
        Neuropharmacology. 1997; 36: 1779-1781
        • Sagar S.M.
        • Sharp F.R.
        • Curran T.
        Expression of c-fos protein in brain: metabolic mapping at the cellular level.
        Science. 1988; 240: 1328-1331
        • Senba E.
        • Uemoto S.
        • Kawai Y.
        • Noguchi K.
        Differential expression of fos family and jun family mRNAs in the rat hypothalamo-pituitary-adrenal axis after immobiliazation stress.
        Brain Res. Mol. Brain Res. 1994; 24: 283-294
        • Shafton A.D.
        • Ryan A.
        • Badoer E.
        Neurons in the hypothalamic paraventricular nucleus send collaterals to the spinal cord and to the rostral ventrolateral medulla in the rat.
        Brain Res. 1998; 801: 239-243
        • Shimizu T.
        • Okada S.
        • Yamaguchi-Shima N.
        • Yokotani K.
        Brain phospholipase C-diacylglycerol lipase pathway is involved in vasopressin-induced release of noradrenaline and adrenaline from adrenal medulla in rats.
        Eur. J. Pharmacol. 2004; 499: 99-105
        • Shimizu T.
        • Okada S.
        • Yamaguchi N.
        • Sasaki T.
        • Lu L.
        • Yokotani K.
        Centrally administered histamine evokes the adrenal secretion of noradrenaline and adrenaline by brain cyclooxygenase-1- and thromboxane A2-mediated mechanisms in rats.
        Eur. J. Pharmacol. 2006; 541: 152-157
        • Shimizu T.
        • Tanaka K.
        • Hasegawa T.
        • Yokotani K.
        Brain α4β2 nicotinic acetylcholine receptors are involved in the secretion of noradrenaline and adrenaline from adrenal medulla in rats.
        Eur. J. Pharmacol. 2011; 654: 241-248
        • Smith W.L.
        • Garavito R.M.
        • Dewitt D.L.
        Prostaglandin endoperoxide H synthases (cyclooxygenase)-1 and -2.
        J. Biol. Chem. 1996; 271: 33157-33160
        • Stocker S.D.
        • Cunningham J.T.
        • Toney G.M.
        Water deprivation increase Fos immunoreactivity in PVN autonomic neurons with projections to the spinal cord and rostral ventrolateral medulla.
        Am. J. Physiol. Regul. Integr. Comp. Physiol. 2004; 287: R1172-R1183
        • Strack A.M.
        • Sawyer W.B.
        • Platt K.B.
        • Loewy A.D.
        CNS cell groups regulating the sympathetic outflow to adrenal gland as revealed by transneuronal cell body labeling with pseudorabies virus.
        Brain Res. 1989; 491: 274-296
        • Strauss K.I.
        • Barbe M.F.
        • Marshall R.M.
        • Raghupathi R.
        • Mehta S.
        • Narayan R.K.
        Prolonged cyclooxygenase-2 induction in neurons and glia following traumatic brain injury in the rat.
        J. Neurotrauma. 2000; 17: 695-711
        • Swanson L.W.
        • Sawchenko P.E.
        Paraventricular nucleus: a site for the integration of neuroendocrine and autonomic mechanisms.
        Neuroendocrinology. 1980; 31: 410-417
        • Tanaka K.
        • Osako Y.
        • Yuri K.
        Juvenile social experience regulates central neuropeptides relevant to emotional and social behaviors.
        Neuroscience. 2010; 166: 1036-1042
        • Tanaka K.
        • Shimizu T.
        • Lu L.
        • Yokotani K.
        Possible involvement of S-nitrosylation of brain cyclooxygenase-1 in bombesin-induced central activation of adrenomedullary outflow in rats.
        Eur. J. Pharmacol. 2012; 679: 40-50
        • Vane J.R.
        • Bakhle Y.S.
        • Botting R.M.
        Cyclooxygenase 1 and 2.
        Annu. Rev. Pharmacol. Toxicol. 1998; 38: 97-120
        • Yamagata K.
        • Andreasson K.I.
        • Kaufman W.E.
        • Barnes C.A.
        • Worley P.F.
        Expression of mitogen-inducible cyclooxygenase in brain neurons; regulation by synaptic activity and glucocorticoids.
        Neuron. 1993; 11: 371-386
        • Yamaguchi N.
        • Okada S.
        • Usui D.
        • Yokotani K.
        Nitric oxide syntase isozymes in spinally projecting PVN neurons are involved in CRF-induced sympathetic activation.
        Auton. Neurosci. 2009; 148: 83-89
        • Yang Z.
        • Coote J.H.
        Influence of the hypothalamic paraventricular nucleus on cardiovascular neurones in the rostral ventrolateral medulla of the rat.
        J. Physiol. 1998; 513: 521-530
        • Yokotani K.
        • Muramatsu I.
        • Fujiwara M.
        • Osumi Y.
        Effects of the sympathoadrenal system on vagally induced gastric acid secretion and mucosal blood flow in rats.
        J. Pharmacol. Exp. Ther. 1983; 224: 436-442
        • Yokotani K.
        • Wang M.
        • Murakami Y.
        • Okada S.
        • Hirata M.
        Brain phospholipase A2-arachidonic acid cascade is involved in the activation of central sympatho-adrenomedullary outflow in rats.
        Eur. J. Pharmacol. 2000; 398: 341-347
        • Yokotani K.
        • Okada S.
        • Nakamura K.
        • Yamaguchi-Shima N.
        • Shimizu T.
        • Arai J.
        • Wakiguchi H.
        • Yokotani K.
        Brain prostanoid TP receptor mediated adrenal noradrenaline secretion and EP3 receptor-mediated sympathetic noradrenaline release in rats.
        Eur. J. Pharmacol. 2005; 512: 29-35
        • Young J.B.
        • Rosa R.M.
        • Landsberg L.
        Dissociation of sympathetic nervous system and adrenal medullary responses.
        Am. J. Physiol. 1984; 247: E35-E40