Neuroinflammatory mechanisms involved in extinction deficits of fear conditioning induced by acute or repeated trauma exposure in mice

• Grant number: 14/21226-0
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: February 01, 2015
• End date: January 31, 2016
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Francisco Silveira Guimaraes
• Grantee: Sabrina Francesca de Souza Lisboa
• Supervisor: Jonathan P. Godbout
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Ohio State University, Columbus, United States
• Associated to the scholarship: 11/22523-0 - Possible neuroinflammatory mechanisms involved in the extinction deficits of conditioning fear following exposing rats to a predator: the role of endocannabinoid system, BP.PD

Abstract

Post-traumatic stress disorder (PTSD), a chronic and debilitating stress-associated neuropsychiatric disorder, develops following exposure to acute or repeated traumatic experiences in a small proportion of individuals. Its vulnerability has been linked to alterations in fear conditioning (FC) processing, in which responses would become exaggerated and/or resistant to extinction. Changes in stress-related brain structures, such as the medial prefrontal cortex, hippocampus and amygdala, could account for the aversive memory persistence. PTSD patients present decreased cortisol levels, probably underlying increased inflammatory responses and altered glucocorticoid receptor sensitivity. Repeated social defeat (RSD) model in mice is useful to modelling some PTSD features and also to activate peripheral inflammatory mechanisms, promoting infiltration of myeloid cells into the brain and neuroinflammation. However, the impact of RSD on FC extinction is unknown. Considering that this is an important feature of PTSD, it will be interesting to evaluate if mice present impairment in this response after RSD. In addition to this model, rat exposure can also induce PTSD-like symptoms in mice, including FC extinction, blunted corticosterone and alteration in brain levels of cytokines. However, it is unknown if neuroinflammation and changes in myeloid cells distribution are involved. It is possible that traumatic experiences induce neuroinflammation and that depend, at least partially, on activation of peripheral immune system. Therefore, the objective of this project is to investigate if acute inescapable (rat exposure) and repeated stress (RSD) promote, in addition to CFC extinction impairment and blunted corticosterone response, changes in the distribution of myeloid cells. Considering that selective serotonin reuptake inhibitors (SSRIs) are used to treat PTSD, we also will evaluate if fluoxetine could attenuate the observed alterations. (AU)