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 Opportunities: Regular Research Grants
• Start date: September 01, 2015
• End date: August 31, 2017
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Carlos Cesar Crestani
• Grantee: Carlos Cesar Crestani
• Host 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

(29)

(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)

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. (12/14376-0, 15/05922-9)

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. (12/14376-0, 15/05922-9, 12/01888-2)

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. (15/05922-9)

BENINI, RICARDO; OLIVEIRA, LEANDRO A.; GOMES-DE-SOUZA, LUCAS; RODRIGUES, BRUNO; CRESTANI, CARLOS C.. Habituation of the cardiovascular response to restraint stress is inhibited by exposure to other stressor stimuli and exercise training. Journal of Experimental Biology, v. 223, n. 8, APR 2020. (15/05922-9, 17/19249-0)

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, p. 12-pg., 2018-10-01. (15/05922-9)

FERREIRA-JUNIOR, NILSON C.; CRESTANI, CARLOS C.; LAGATTA, DAVI C.; RESSTEL, LEONARDO B. M.; CORREA, FERNANDO M. A.; ALVES, FERNANDO H. F.. Nitric oxide in the insular cortex modulates baroreflex responses in a cGMP- independent pathway. Brain Research, v. 1747, p. 8-pg., 2020-11-15. (15/05922-9)

OLIVEIRA, LEANDRO A.; GOMES-DE-SOUZA, LUCAS; BENINI, RICARDO; WOOD, SUSAN K.; CRESTANI, CARLOS C.. Both CRF1 and CRF2 receptors in the bed nucleus of stria terminalis are involved in baroreflex impairment evoked by chronic stress in rats. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 105, MAR 8 2021. (17/19249-0, 15/05922-9)

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. (15/05922-9, 16/05218-2, 17/19249-0)

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. (15/05922-9, 16/05218-2, 16/05028-9, 17/19249-0)

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. (12/14376-0, 15/05922-9)

ALMEIDA, JEFERSON; OLIVEIRA, LEANDRO A.; BENINI, RICARDO; CRESTANI, CARLOS C.. Role of hippocampal nitrergic neurotransmission in behavioral and cardiovascular dysfunctions evoked by chronic social stress. NITRIC OXIDE-BIOLOGY AND CHEMISTRY, v. 94, p. 114-124, JAN 1 2020. (15/05922-9, 17/19249-0)

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. (15/05922-9, 17/19249-0)

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. (17/19249-0, 15/05922-9)

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. (12/14376-0, 15/05922-9)

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. (15/05922-9)

SANTOS, CARLOS E.; BENINI, RICARDO; CRESTANI, CARLOS C.. Spontaneous recovery, time course, and circadian influence on habituation of the cardiovascular responses to repeated restraint stress in rats. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, v. 472, n. 10, AUG 2020. (15/05922-9, 17/19249-0)

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. (17/19249-0, 15/05922-9)

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. (15/05922-9)

GOMES-DE-SOUZA, LUCAS; COSTA-FERREIRA, WILLIAN; OLIVEIRA, LEANDRO A.; BENINI, RICARDO; CRESTANI, CARLOS C.. Cannabinoid receptor type 1 in the bed nucleus of the stria terminalis modulates cardiovascular responses to stress via local N-methyl-D-aspartate receptor/neuronal nitric oxide synthase/soluble guanylate cyclase/protein kinase G signaling. JOURNAL OF PSYCHOPHARMACOLOGY, v. 34, n. 4, JAN 2020. (15/05922-9, 17/19249-0)

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. (17/19249-0, 15/05922-9)

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. (12/14376-0, 13/01283-6, 15/05922-9)

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. (12/14376-0, 15/05922-9)

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. (12/14376-0, 15/05922-9)

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. (12/14376-0, 15/05922-9)

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. (15/05922-9)

COSTA-FERREIRA, WILLIAN; GOMES-DE-SOUZA, LUCAS; CRESTANI, CARLOS C.. Role of angiotensin receptors in the medial amygdaloid nucleus in autonomic, baroreflex and cardiovascular changes evoked by chronic stress in rats. European Journal of Neuroscience, v. 53, n. 3, JAN 2021. (15/05922-9, 17/19249-0)

DUARTE, JOSIANE O.; PLANETA, CLEOPATRA S.; CRESTANI, CARLOS C.. Vulnerability and resilience to cardiovascular and neuroendocrine effects of stress in adult rats with historical of chronic stress during adolescence. Life Sciences, v. 318, p. 11-pg., 2023-02-15. (12/14376-0, 15/05922-9, 19/24478-3)

GOULART, MELISSA T.; BUSNARDO, CRISTIANE; BELEM-FILHO, IVALDO J. A.; BENINI, RICARDO; FASSINI, ALINE; CRESTANI, CARLOS C.; GODOY, ANA C.; CORREA, FERNANDO M. A.; ALVES, FERNANDO H. F.. NMDA receptors in the insular cortex modulate cardiovascular and autonomic but not neuroendocrine responses to restraint stress in rats. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 119, p. 10-pg., 2022-07-14. (21/00148-4, 18/04899-1, 15/05922-9, 17/19249-0)

CRESTANI, CARLOS C.. Adolescent vulnerability to cardiovascular consequences of chronic emotional stress: Review and perspectives for future research. NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, v. 74, p. 10-pg., 2017-03-01. (12/14376-0, 15/05922-9)