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Study of the participation of CRF neurotransmission in the bed nucleus of the stria terminalis in cardiovascular changes evoked by stress: interaction with the NMDA receptor/nitric oxide / guanilil cycles / protein kinase g signaling pathway?

Grant number: 15/05922-9
Support type:Regular Research Grants
Duration: September 01, 2015 - August 31, 2017
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Carlos Cesar Crestani
Grantee:Carlos Cesar Crestani
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Clinical and preclinical studies have demonstrated a role of stress in the pathogenesis of several cardiovascular diseases. However, the neurobiological mechanisms involved in cardiovascular complications related to stress is poorly understood. The bed nucleus of the stria terminalis (BNST) is a limbic structure localized in the rostral prosencephalon, which has been implicated in stress-evoked neuroendocrine, behavioral and cardiovascular responses. It has been reported an involvement of corticotropin-releasing factor (CRF) neurotransmission within the BNST in cardiovascular responses observed during acute stress sessions. However, although reports of neuroplasticity in BNST CRF neurotransmission following exposure to chronic stress protocols, a possible involvement of this neurochemical mechanism in cardiovascular changes evoked by chronic stressors has never been evaluated. Chronic stress exposure evokes several cardiovascular changes, which seem to play an important role in etiology of stress-evoked cardiovascular diseases. Therefore, one of the hypotheses to be tested in the present study is that BNST CRF neurotransmission is involved in cardiovascular changes evoked by chronic stress.Recent studies have demonstrated that activation of CRF1 receptors within the BNST facilitates local glutamatergic neurotransmission. An important mechanism of nitric oxide (NO) formation in the central nervous system is mediated by activation of the NMDA glutamatergic receptor, which in turn activates the neuronal isoform of the NO synthases enzyme (nNOS). The NO has several signaling mechanisms, but the main is mediated by stimulation of cyclic guanosine monophosphate (cGMP) formation that in turn activates protein kinase G. Although above evidence, a possible involvement of local glutamatergic and nitrergic signaling in regulation of cardiovascular function by BNST CRF neurotransmission has never been investigated. Therefore, a second hypothesis to be tested in the present study is that the control of cardiovascular responses during an acute stress session by BNST CRF1 receptor is mediated by local glutamatergic neurotransmission, acting via NMDA receptors and dependent of NO formation and activation of the soluble guanylate ciclase and protein kinase G.Therefore, the aims of the present study are: 1) to evaluate the involvement of BNST CRF neurotransmission in changes of baroreflex activity evoked by the chronic variable stress (CVS); 2) to study the involvement of BNST CRF neurotransmission in cardiovascular hiperesponsivity to an acute stressor evoked by the CVS; 3) to investigate the role of the NMDA receptor/NO/guanylate cyclase/protein kinase G signaling pathway in control of cardiovascular responses to acute restraint stress by the CRF1 receptor within the BNST. (AU)

Scientific publications (18)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
COSTA-FERREIRA, WILLIAN; GOMES-DE-SOUZA, LUCAS; CRESTANI, CARLOS C. AT(2) and MAS (but not AT(1)) angiotensinergic receptors in the medial amygdaloid nucleus modulate the baroreflex activity in rats. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, v. 471, n. 9, p. 1173-1182, SEP 2019. Web of Science Citations: 0.
COSTA-FERREIRA, MILIAN; MORAIS-SILVA, GESSYNGER; GOMES-DE-SOUZA, LUCAS; MARIN, MARCELO T.; CRESTANI, CARLOS C. The AT1 Receptor Antagonist Losartan Does Not Affect Depressive-Like State and Memory Impairment Evoked by Chronic Stressors in Rats. FRONTIERS IN PHARMACOLOGY, v. 10, JUN 21 2019. Web of Science Citations: 0.
ALMEIDA, JEFERSON; OLIVEIRA, LEANDRO A.; BENINI, RICARDO; CRESTANI, CARLOS C. Differential roles of hippocampal nNOS and iNOS in the control of baroreflex function in conscious rats. Brain Research, v. 1710, p. 109-116, MAY 1 2019. Web of Science Citations: 0.
GOMES-DE-SOUZA, LUCAS; BENINI, RICARDO; COSTA-FERREIRA, WILLIAN; CRESTANI, CARLOS C. GAB(A) but not GABA(B) receptors in the lateral hypothalamus modulate the tachycardic response to emotional stress in rats. European Neuropsychopharmacology, v. 29, n. 5, p. 672-680, MAY 2019. Web of Science Citations: 0.
BENINI, RICARDO; OLIVEIRA, LEANDRO A.; GOMES-DE-SOUZA, LUCAS; CRESTANI, CARLOS C. Habituation of the cardiovascular responses to restraint stress in male rats: influence of length, frequency and number of aversive sessions. STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS, v. 22, n. 1, p. 151-161, JAN 2 2019. Web of Science Citations: 1.
VIEIRA, JONAS O.; DUARTE, JOSIANE O.; COSTA-FERREIRA, WILLIAN; CRESTANI, CARLOS C. Influence of pre-existing hypertension on neuroendocrine and cardiovascular changes evoked by chronic stress in female rats. PSYCHONEUROENDOCRINOLOGY, v. 97, p. 111-119, NOV 2018. Web of Science Citations: 1.
BARRETTO-DE-SOUZA, LUCAS; ADAMI, MARIANE B.; BENINI, RICARDO; CRESTANI, CARLOS C. Dual role of nitrergic neurotransmission in the bed nucleus of the stria terminalis in controlling cardiovascular responses to emotional stress in rats. British Journal of Pharmacology, v. 175, n. 19, p. 3773-3783, OCT 2018. Web of Science Citations: 1.
HECK, A. L.; CRESTANI, C. C.; FERNANDEZ-GUASTI, A.; LARCO, D. O.; MAYERHOFER, A.; ROSELLI, C. E. Neuropeptide and steroid hormone mediators of neuroendocrine regulation. Journal of Neuroendocrinology, v. 30, n. 10, SI OCT 2018. Web of Science Citations: 2.
OLIVEIRA, LEANDRO A.; GOMES-DE-SOUZA, LUCAS; BENINI, RICARDO; CRESTANI, CARLOS C. Control of cardiovascular responses to stress by CRF in the bed nucleus of stria terminalis is mediated by local NMDA/nNOS/sGC/PKG signaling. PSYCHONEUROENDOCRINOLOGY, v. 89, p. 168-176, MAR 2018. Web of Science Citations: 2.
VIEIRA, JONAS O.; DUARTE, JOSIANE O.; COSTA-FERREIRA, WILLIAN; MORAIS-SILVA, GESSYNGER; MARIN, MARCELO T.; CRESTANI, CARLOS C. Sex differences in cardiovascular, neuroendocrine and behavioral changes evoked by chronic stressors in rats. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 81, p. 426-437, FEB 2 2018. Web of Science Citations: 16.
BARRETTO-DE-SOUZA, LUCAS; ADAMI, MARIANE B.; OLIVEIRA, LEANDRO A.; GOMES-DE-SOUZA, LUCAS; DUARTE, JOSIANE O.; ALMEIDA, JEFERSON; CRESTANI, CARLOS C. Nitric oxide-cGMP-PKG signaling in the bed nucleus of the stria terminalis modulates the cardiovascular responses to stress in male rats. European Neuropsychopharmacology, v. 28, n. 1, p. 75-84, JAN 2018. Web of Science Citations: 2.
OLIVEIRA, LEANDRO A.; ALMEIDA, JEFERSON; GOMES-DE-SOUZA, LUCAS; BENINI, RICARDO; CRESTANI, CARLOS C. CRF1 and CRF2 receptors in the bed nucleus of stria terminalis differently modulate the baroreflex function in unanesthetized rats. European Journal of Neuroscience, v. 46, n. 2, p. 1805-1812, JUL 2017. Web of Science Citations: 1.
DUARTE, JOSIANE O.; GOMES, KARINA S.; NUNES-DE-SOUZA, RICARDO L.; CRESTANI, CARLOS C. Role of the lateral preoptic area in cardiovascular and neuroendocrine responses to acute restraint stress in rats. Physiology & Behavior, v. 175, p. 16-21, JUN 1 2017. Web of Science Citations: 4.
ADAMI, MARIANE B.; BARRETTO-DE-SOUZA, LUCAS; DUARTE, JOSIANE O.; ALMEIDA, JEFERSON; CRESTANI, CARLOS C. Both N-methyl-D-aspartate and non-N-methyl-D-aspartate glutamate receptors in the bed nucleus of the stria terminalis modulate the cardiovascular responses to acute restraint stress in rats. JOURNAL OF PSYCHOPHARMACOLOGY, v. 31, n. 6, p. 674-681, JUN 2017. Web of Science Citations: 5.
CRESTANI, CARLOS C. Adolescent vulnerability to cardiovascular consequences of chronic emotional stress: Review and perspectives for future research. NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, v. 74, n. B, SI, p. 466-475, MAR 2017. Web of Science Citations: 6.
GOMES-DE-SOUZA, LUCAS; OLIVEIRA, LEANDRO A.; BENINI, RICARDO; RODELLA, PATRICIA; COSTA-FERREIRA, WILLIAN; CRESTANI, CARLOS C. Involvement of endocannabinoid neurotransmission in the bed nucleus of stria terminalis in cardiovascular responses to acute restraint stress in rats. British Journal of Pharmacology, v. 173, n. 19, p. 2833-2844, OCT 2016. Web of Science Citations: 7.
COSTA-FERREIRA, WILLIAN; VIEIRA, JONAS O.; ALMEIDA, JEFERSON; GOMES-DE-SOUZA, LUCAS; CRESTANI, CARLOS C. Involvement of Type 1 Angiontensin II Receptor (AT(1)) in Cardiovascular Changes Induced by Chronic Emotional Stress: Comparison between Homotypic and Heterotypic Stressors. FRONTIERS IN PHARMACOLOGY, v. 7, AUG 18 2016. Web of Science Citations: 8.
GOUVEIA, MARIANNA K.; MIGUEL, TARCISO T.; BUSNARDO, CRISTIANE; SCOPINHO, AMERICA A.; CORREA, FERNANDO M. A.; NUNES-DE-SOUZA, RICARDO L.; CRESTANI, CARLOS C. Dissociation in control of physiological and behavioral responses to emotional stress by cholinergic neurotransmission in the bed nucleus of the stria terminalis in rats. Neuropharmacology, v. 101, p. 379-388, FEB 2016. Web of Science Citations: 9.

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