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Artificial and biological astrocytes in a model of chronic stress: behavioral, immunohistochemical and electrophysiological effects

Grant number: 19/26777-8
Support type:Regular Research Grants
Duration: July 01, 2020 - June 30, 2022
Field of knowledge:Humanities - Psychology - Physiological Psychology
Principal researcher:Milena de Barros Viana
Grantee:Milena de Barros Viana
Home Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil
Assoc. researchers: Ana Maria Ferreira de Sousa Sebastião ; Isabel Cristina Céspedes ; Sandra Cristina Henriques Vaz

Abstract

The concept of stress is based on the observation that different types of stimuli (endogenous or extern to the subject), that might threaten the organism homeostasis, activate a series of physiological alterations named "general adaptation syndrome". The term stimulus (or stressor) corresponds to the events or circunstances that are perceived as aversive by the subject and that generate the stress response, which involves visceral, neuroendocrine and behavioral reactions. Thee stress response is aimed to restore homeostasis/allostasis and is by itself not pathological. Nevertheless, when the aversive stimulation occurs for a prolonged period or excedes the capacity of the organism to maintain homeostasis/allostasis, stress may cause pathological alterations, such as anxiety and depression, stress-related psychopathologies. It is well established that the glutamatergic system contributes to the physiopathology of these conditions. It has been demonstrated, for instance, that exposure to stress, one of the main precipitant factor of anxiety and depression disorders, increases the release of glutamate, alters astrocytes function and causes structural damage to the ventral hippocampus, an important brain region that regulares the stress response. During the last years, synthetic biology has emerged as an important field for therapeutic applications. A critical contribution from this area of research is the development of micro and nano structures, with size, form, and chemical and biological activity adjustable, including artificial cells, organelles and enzymes , the so-called micro or nanoreactors. It has been demonstrated that some of these substances, equipped with glutamate desidrogenase and glutation redutase are capable of decreasing excitotoxicity, consuming the excess of glutamate produced and reducing glutation. In this sense, the main purpose of the present project is to investigate the activity of these micro-reactors administered intra ventral hippocampus of animals submitted or not to the blockage of the astrocytary function, and exposed or not to mild chronic unpredictable stress (UCMS). For that, male Wistar rats will be submitted or not to UCMS for 14 consecutive days and on the 15th day injected intra-ventral hippocampus with micro-reactors or vehicle solution. A group of animals will also be submitted to the blockage of the astrocytary function. Five days after the injection, the animals will be tested in the elevated T-maze and open field model (animal models of anxiety and locomotor activity) or to the forced swim (an animal model of depression). Immediately after behavioral testing, animals will be sacrificed and their brains processed for immunohistochemical evaluation of neurons and glial cells. An additional group of animals will be submitted to the evaluation of the electrophysiological activity of the ventral hippocampus, to allow a better understanding of how chronic stress and the treatment with micro-reactors interfere with the electrophysiology of the investigated structure. Last but not least, it is important to add that one of the main objectives of the present project is to allow the maintenance of the collaboration between the proponents research group and the research group under the supervision of Dr. Ana Maria Sebastião, at Universidade de Lisboa, a collaboration which already began with a research project previously conducted by the proponent, with FAPESP fundings. (AU)

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