Role of the insular cortex in control of the cardiovascular and anxiogenic responses to stress in rats: evaluation of functional topography and involvement of corticotropin-releasing factor (CRF) neurotransmission

• Grant number: 19/24478-3
• Support Opportunities: Regular Research Grants
• Duration: September 01, 2020 - August 31, 2022
• 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

Stress is identified as a prominent factor involved in the pathogenesis of various diseases. Despite the relevance of the theme, the neurobiological mechanisms related to stress-induced cardiovascular and behavioral changes are still poorly understood. In this sense, the insular cortex (IC) has been implicated in the integration and processing of limbic information in humans and animals. In fact, an involvement of IC in cardiovascular and behavioral responses to stress has been reported. However, a possible rostro-caudal organization in control of stress responses by IC has never been investigated. This is a relevant aspect, since studies in humans and animals have reported functional dissociation along the rostro-caudal axis of the IC in control of cardiovascular function and sensory responses. Thus, a first proposal of the present study is to evaluate the functional topography of the IC in control of cardiovascular and anxiogenic responses to acute restraint stress. Another relevant aspect is that the local neurochemical mechanisms involved in control of stress responses by the IC was poorly explored. In this sense, corticotropin-releasing factor (CRF) neurotransmission has been reported to be an important mechanism in the central nervous system involved in the etiology of behavioral changes and physiological adjustments observed during exposure to aversive threats. However, the specific brain sites whereby CRF neurotransmission acts to control stress responses are still poorly understood. CRF-containing terminals as well as the CRF1 receptor were identified within the IC. However, a possible involvement of this IC neurochemical mechanism in control of stress-induced physiological and behavioral responses has never been investigated. Thus, a second proposal of the present study is to evaluate the participation of CRF in the IC, acting through local CRF1 receptor activation, in control of the cardiovascular and anxiogenic responses evoked by acute restraint stress in rats. Finally, it has also been reported that repeated exposure to aversive events alters CRF and CRF1 receptor expression in various limbic structures. However, a possible effect of chronic stress on CRFergic neurotransmission within the IC has never been investigated. Thus, a final proposal of the present project is to investigate whether repeated exposure to restraint stress causes changes in IC CRFergic neurotransmission, and whether these changes affect the control of restraint-evoked cardiovascular and anxiogenic responses by this neurochemical mechanism in the IC. (AU)

Scientific publications

(10)

(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.; POLLO, TACIANA R. S.; ROSA, ELINEIA A.; DUARTE, JOSIANE O.; XAVIER, CARLOS H.; CRESTANI, CARLOS C.. Both Prelimbic and Infralimbic Noradrenergic Neurotransmissions Modulate Cardiovascular Responses to Restraint Stress in Rats. FRONTIERS IN PHYSIOLOGY, v. 12, AUG 12 2021. (19/24478-3, 12/14376-0)

XAVIER, CARLOS HENRIQUE; DE MENEZES, RODRIGO CUNHA ALVIM; CHIANCA, DEOCLECIO ALVES; FONTES, MARCO ANTONIO PELIKY; CRESTANI, CARLOS CESAR. Editorial: Stress-Related Diseases and Dysfunctions. FRONTIERS IN PHYSIOLOGY, v. 13, p. 3-pg., 2022-04-12. (17/19249-0, 19/24478-3)

MARCHI-COELHO, CAMILA; COSTA-FERREIRA, WILLIAN; REIS-SILVA, LILIAN L.; CRESTANI, CARLOS C.. Angiotensinergic Neurotransmissions in the Medial Amygdala Nucleus Modulate Behavioral Changes in the Forced Swimming Test Evoked by Acute Restraint Stress in Rats. CELLS, v. 10, n. 5, MAY 2021. (18/23686-9, 19/24478-3, 16/05218-2)

VITORIO, ALEX S.; REIS-SILVA, LILIAN L.; BARRETTO-DE-SOUZA, LUCAS; GOMES-DE-SOUZA, LUCAS; CRESTANI, CARLOS C.. Evaluation of the posterior insular cortex involvement in anxiogenic response to emotional stress in male rats: Functional topography along the rostrocaudal axis. Physiology & Behavior, v. 258, p. 7-pg., 2023-01-01. (19/24478-3)

OLIVEIRA, LEANDRO A.; CARVALHO, IVY I.; KUROKAWA, RENATA Y.; DUARTE, JOSIANE DE O.; BUSNARDO, CRISTIANE; CRESTANI, CARLOS C.. Differential roles of prelimbic and infralimbic cholinergic neurotransmissions in control of cardiovascular responses to restraint stress in rats. Brain Research Bulletin, v. 181, p. 8-pg., 2022-02-07. (19/24478-3, 12/14376-0)

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)

TOMEO, RODRIGO A.; GOMES-DE-SOUZA, LUCAS; BENINI, RICARDO; REIS-SILVA, LILIAN L.; CRESTANI, CARLOS C.. Site-Specific Regulation of Stress Responses Along the Rostrocaudal Axis of the Insular Cortex in Rats. FRONTIERS IN NEUROSCIENCE, v. 16, p. 12-pg., 2022-05-10. (19/24478-3, 17/19249-0)

GOMES-DE-SOUZA, LUCAS; COSTA-FERREIRA, WILLIAN; MENDONCA, MICHELLE M.; XAVIER, CARLOS H.; CRESTANI, CARLOS C.. Lateral hypothalamus involvement in control of stress response by bed nucleus of the stria terminalis endocannabinoid neurotransmission in male rats. SCIENTIFIC REPORTS, v. 11, n. 1, AUG 9 2021. (16/05028-9, 16/05218-2, 19/24478-3, 17/19249-0)

BARRETTO-DE-SOUZA, LUCAS; BENINI, RICARDO; REIS-SILVA, LILIAN LIZ; CRESTANI, CARLOS C.. Role of CRF1 and CRF2 receptors in the lateral hypothalamus in cardiovascular and anxiogenic responses evoked by restraint stress in rats: Evaluation of acute and chronic exposure. Neuropharmacology, v. 212, p. 14-pg., 2022-07-01. (17/19249-0, 19/24478-3)

CRESTANI, CARLOS C.; TOMEO, RODRIGO A.; GOMES-DE-SOUZA, LUCAS; BENINI, RICARDO; REIS-SILVA, LILIAN L.. Site-specific regulation of emotional stress responses along the rostrocaudal axis of the insular cortex in rats. FASEB JOURNAL, v. 36, p. 1-pg., 2022-01-01. (19/24478-3, 17/19249-0)