Genetic study of hypocampus glutamate neurotransmission in central mechanisms of the adaptation of neuroendocrine, cardiovascular and behavioral responses to repeated chronic stress and stress-induced neuroinflamation

• Grant number: 18/04899-1
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: February 01, 2021
• End date: January 31, 2027
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Cristiane Busnardo Santiago
• Grantee: Cristiane Busnardo Santiago
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated researchers: Carlos Cesar Crestani ; Fabio Cardoso Cruz ; Fernando Morgan de Aguiar Correa ; James Paul Herman
• Associated scholarship(s): 23/12262-1 - Study of the effect of inhibition of glutamatergic neurons in the ventral hippocampus on cognitive changes induced by repeated restraint stress, BP.IC; 23/00306-4 - Study of the effect of inactivating previously activated neurons in the hippocampus during repeated chronic stress in c-fos-lacZ transgenic rats on the habituation process of autonomic, neuroendocrine and neuroinflammatory responses, BP.DD; 21/06709-8 - Genetic study of glutamatergic neurotransmission in ventral hippocampus on baseline cardiovascular parameters, cardiac autonomic activity, baroreflex activity, neuroendocrine and behavioral parameters during chronic repeated stress, BP.MS; 21/04572-5 - Study of hippocampal neurotransmission involvement in the central mechanisms of chronic repeated stress-induced behavioral responses, BP.IC; 21/00148-4 - Genetic study of hypocampus glutamate neurotransmission in central mechanisms of the adaptation of neuroendocrine, cardiovascular and behavioral responses to repeated chronic stress and stress-induced neuroinflamation, BP.JP

Abstract

Emotional stress has caused a physiological and psychological imbalance, and it has been associated with several pathologies, including cardiovascular diseases and psychiatric disorders. Adaptive processes are triggered during prolonged or repeated exposure to stress, in which they are important to minimize the impact of stress on the body. An important adaptation is a habituation of physiological responses (e.g., hypothalamic-pituitary-adrenal (HPA) axis stimulation and neural activation) during a repeated exposure to the same aversive stimulus. However, despite the importance of habituation of stress responses, the neurobiological and neurochemical mechanisms involved in this process are still poorly understood. In this sense, it has been demonstrated a functional interaction between glutamatergic and nitrergic neurotransmissions in the hippocampus in the regulation of autonomic, HPA axis and / or behavioral responses to acute stress. However, a possible involvement of this signaling mechanism in the habituation process during repeated exposure to stress situations has never been investigated. In addition, glucocorticoids and neurotransmitters such as glutamate released into the central nervous system (CNS) during stress induce a local release of proinflammatory cytokines, which may lead to long-term behavioral consequences, such as depressive-type behaviors, being considered a poor adaptation to stress. So, the study of cytokine release is essential for understanding the effects of stress on the CNS. Therefore, the goal of the present project is to evaluate the effect of chemogenic silencing (through the use of DREADDs) of glutamatergic neurons in the ventral and dorsal hippocampus on habituation of autonomic, neuroendocrine, behavioral and neuroinflammatory responses related to exposure restraint stress. As a DREADD technology is used to inactivate glutamatergic neurons independent of their activation state, it will be also used the Daun02 inactivation method in transgenic c-Fos lacZ rat that inactivates only neurons that were previously activated during a specific behavior. In this sense, we will also evaluate the inactivation of ventral and dorsal hippocampal neurons previously activated by restraint stress on the habituation of autonomic, neuroendocrine, behavioral and neuroinflammatory responses associated with chronic restraint stress. (AU)

Scientific publications

(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)

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)

BELEM-FILHO, IVALDO J. A.; GODOY, ANA C. V.; BUSNARDO, CRISTIANE; FRIAS, ALANA T.; ZANGROSSI JR, HELIO; BORGES, BRUNO DEL BIANCO; HERVAL, ANA C. F.; CORREA, FERNANDO M. A.; CRESTANI, CARLOS C.; ALVES, FERNANDO H. F.. Role of endocannabinoid neurotransmission in the insular cortex on cardiovascular, autonomic and behavioral responses evoked by acute restraint stress in rats. Neuropharmacology, v. 271, p. 13-pg., 2025-03-07. (21/10014-5, 18/04899-1)

BUSNARDO, CRISTIANE; FASSINI, ALINE; RODRIGUES, BRUNO; ANTUNES-RODRIGUES, JOSE; CRESTANI, CARLOS C.; CORREA, FERNANDO M. A.. N-Methyl-D-aspartate Glutamate Receptor Modulates Cardiovascular and Neuroendocrine Responses Evoked by Hemorrhagic Shock in Rats. BIOMED RESEARCH INTERNATIONAL, v. 2021, AUG 13 2021. (13/00249-9, 21/00148-4, 18/04899-1)