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Microglia under stress in brain development: setting the grounds for anxiety and depression
Portugal (PorMSIC) - University of Coimbra, Coimbra
Institute of Pharmacology and Experimental Therapeutics
Antonio Francisco Ambrosio
Catarina A. dos Reis Vale Gomes
Type of Research Project
- Basic science
What is the background of the project?
Developmental risk factors contribute to the pathophysiology of anxiety disorders, namely the exposure to high levels of glucocorticoids, associated with early life stress or glucocorticoid therapies. The immunomodulatory role of glucocorticoids raises the question whether chronic anxiety and susceptibility to depression described in individuals exposed in utero to high glucocorticoids (iuGC) are due to a direct neuronal impact, or account for changes in glial immune cells - microglia, which actively regulate synapse formation and brain wiring during neurodevelopment. This project tackles the global working hypothesis that stress mediators during development trigger changes in microglia, which may be determinant in the pathophysiology of anxiety and susceptibility to depression.
What is the aim of the project?
The main goals of this project are to define: (1) if microglial changes contribute to the susceptibility to depression in anxious animals prenatally exposed to high levels of glucocorticoids; (2) if changes in microglial cells account for the efficacy of antidepressants commonly used to treat chronic anxiety and depression (selective serotonin reuptake inhibitors, e.g. fluoxetine and tricyclic agents, e.g. imipramine).
What techniques and methods are used?
In animals exposed in utero to the glucocorticoid dexamethasone: (1) evaluation of the short- and long-term impact of iuGC on microglial/neuronal morphology in the mPFC, hippocampus and amygdala (analysis of neurons and microglia in brain slices from the pre-frontal cortex - PFC -, amygdala and hippocampus, crucial regions for anxiety and depression; brain slices will be processed for immunohistochemistry and Golgi staining, followed by 3D reconstruction of these cells using the software Neurolucida); (2) behavioral tests for depression (forced swimming tests) and anxiety (elevated plus maze).
What is the role of the student?
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
Immunohistochemical procedures (labeling microglial cells and neurons); Golgi staining (neurons); 3D reconstruction of cells and determination of morphometric analysis of brain cells in the parenchyma (softweare Neurolucida); behavioral tests
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a poster - The student will prepare a presentation
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students
- Oliveira M; Bessa JM; (1) Mesquita A; Tavares H; Carvalho A; Silva R; P
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