Dealing with the enemy: effects of the treatment with N-acetylcysteine in the susceptibility and resilience to the social defeat stress in rats

• Grant number: 15/25308-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2016
• End date: March 31, 2021
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Marcelo Tadeu Marin
• Grantee: Gessynger Morais Silva
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated scholarship(s): 18/05496-8 - Role of the ventral pallido-accumbal projections in the susceptibility to social defeat stress, BE.EP.DR

Abstract

Stress is a general response of the body to exposure to noxious stimuli, which, if prolonged, may lead to the development of cognitive disorders, mood disorders and cardiovascular problems. Nevertheless, not every individual exposed to stress develops diseases. This individual difference may be related to an individual's ability to adapt to aversive events, i.e. their resilience or susceptibility to stress. The model of social defeat stress (SDS) has predictive and face validity, ethological relevance and similarity to psychosocial stress experienced by humans. After exposure of rodents to SDS, two phenotypes are clearly perceived: one susceptible, that present decreased social interaction and behavioral changes related to depression, and a resilient, that does not show these changes. These phenotypes can be objectively separated by the social interaction test. In addition, these animals have different neural changes after SDS exposure. Evidence suggests an important role of the transcriptional factor ”FosB in resilience to stress and changes in the balance of glutamatergic neurotransmission due to stress exposure may be related to the development of stress-related diseases. N-acetylcysteine (N-AC), a pro-drug which leads to an increase in extrasynaptic glutamate concentration through the activation of cystine-glutamate exchanger (xCT) has shown promising results in the treatment of stress-related disorders. Thus, the aim of this study will be the evaluation of the behavioral changes related to memory, depression and anxiety, cardiovascular changes and the amount of ”FosB and xCT proteins in phenotypes resilient and susceptible of rats exposed to SDS and the evaluation of the effects of the treatment with N -AC in these changes.

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)

MORAIS-SILVA, GESSYNGER; GOMES-DE-SOUZA, LUCAS; COSTA-FERREIRA, WILLIAN; PAVAN, JACQUELINE C.; CRESTANI, CARLOS C.; MARIN, MARCELO T.. ardiovascular Reactivity to a Novel Stressor: Differences on Susceptible and Resilient Rats to Social Defeat Stres. RONTIERS IN PHYSIOLOG, v. 12, FEB 16 2022. (15/25308-3)

MORAIS-SILVA, GESSYNGER; COSTA-FERREIRA, WILLIAN; GOMES-DE-SOUZA, LUCAS; PAVAN, JACQUELINE C.; CRESTANI, CARLOS C.; MARIN, MARCELO T.. Cardiovascular outcomes related to social defeat stress: New insights from resilient and susceptible rats. NEUROBIOLOGY OF STRESS, v. 11, NOV 2019. (15/25308-3)

MORAIS-SILVA, GESSYNGER; CAMPBELL, RIANNE R.; NAM, HYUNGWOO; BASU, MAHASHWETA; PAGLIUSI, MARCO; FOX, MEGAN E.; CHAN, C. SAVIO; INIGUEZ, SERGIO D.; AMENT, SETH; CRAMER, NATHAN; et al. Molecular, Circuit, and Stress Response Characterization of Ventral Pallidum Npas1-Neurons. JOURNAL OF NEUROSCIENCE, v. 43, n. 3, p. 14-pg., 2023-01-18. (15/25308-3, 18/05496-8)