Escola Paulista de Medicina
Postgraduate Program in Pharmacology

NEUROPSYCHOPHARMACOLOGY, NEUROPLASTICITY AND AGING:Projects

Projects of the NEUROPSYCHOPHARMACOLOGY, NEUROPLASTICITY AND AGING Research Line of the Postgraduate Program in Pharmacology:

BEHAVIORAL AND NEUROBIOLOGICAL ASPECTS OF NEURODEGENERATIVE AND PSYCHIATRIC DISORDERS IN ANIMAL MODELS

BEHAVIORAL AND NEUROBIOLOGICAL ASPECTS OF NEURODEGENERATIVE AND PSYCHIATRIC DISORDERS IN ANIMAL MODELS

The project aims to investigate motor, cognitive and emotional behaviors related to neurodegenerative and psychiatric disorders in animal models, as well as their relationship with markers of neurotransmission systems, cell degeneration and plasma levels of steroid hormones.

Professor: Regina Helena da Silva

SCHIZOPHRENIA AND AUTISM: PATHOPHYSIOLOGY, TREATMENT AND PREVENTION

SCHIZOPHRENIA AND AUTISM: PATHOPHYSIOLOGY, TREATMENT AND PREVENTION

Schizophrenia and autism are neurodevelopmental disorders that constitute a challenge to neuropsychiatry. Pathopshysiological mechanisms are related to alterations in neurotransmissions as well as in neuroprogressive processes. Treatments are limited by incomplete efficacy to improve or prevent the symptoms, side-effects and refractoriness in a considerable proportion of patients. Therefore, the study of pathophysiological mechanisms as well as the search for safe innovative treatment and preventive strategies are fundamental. The main targets of investigation are the dopaminergic, glutamatergic, gabaergic, cannabinoid and nitrergic neurotransmissions as well as neuroinflammation, oxidative stress and cell death processes. For these purposes, behavioral, neurochemical and/or molecular evaluations are conducted in cellular and animal models.

Professor: Vanessa Costhek Abilio

BEHAVIORAL AND MOLECULAR INVESTIGATION OF THE MECHANISMS INVOLVED WITH THE SUBSTANCE USE DISORDERS

BEHAVIORAL AND MOLECULAR INVESTIGATION OF THE MECHANISMS INVOLVED WITH THE SUBSTANCE USE DISORDERS

Evidence shows that addiction involves learning associative behaviors. During the drug use, people learn to associate the drug reward effects with contextual cues. It is well known that learned associations are encoded within sparsely distributed patterns of neurons, now called neuronal ensembles. Based on these considerations, we propose to combine some methodologies, considered as state-of-art (optogenetic, chemogenetic, FACS, trangenic animals, viral vectors, and others) to assess different aspects of ensemble-specific neuroadaptations in different behaviors related to the substance use disorder. 

Professor: Fabio Cardoso Cruz

ARTIFICIAL AND BIOLOGICAL ASTROCYTES IN A CHRONIC STRESS MODEL: BEHAVIORAL, IMMUNOISTOCHEMICAL AND ELECTROPHYSIOLOGICAL EFFECTS

ARTIFICIAL AND BIOLOGICAL ASTROCYTES IN A CHRONIC STRESS MODEL: BEHAVIORAL, IMMUNOISTOCHEMICAL AND ELECTROPHYSIOLOGICAL EFFECTS

Chronic stress can lead to pathological sequelae, such as anxiety and depression, which are understood as stress-related psychiatric disorders. It is well established that the glutamatergic system contributes to the pathophysiology of these disorders. It has been shown, for example, that exposure to stress, one of the main precipitating factors of anxiety disorders and depression, increases glutamate release, alters astrocytic function and causes structural damage to the ventral hippocampus, an important brain structure for regulation of the stress response. In recent years, synthetic biology has emerged as a promising therapeutic field. A central focus of this area is the fabrication of micro and nanostructures with adjustable size, shape, chemistry and biological activity, including the assembly of artificial cells, organelles and enzymes, the so-called micro or nanoreactors. It has been shown that some of these substances, equipped with glutamate dehydrogenase and glutathione reductase, are able to reduce excitotoxicity, consuming excess glutamate accumulated and generating reduced glutathione. In this sense, the general objective of this project is to investigate the activity of these microreactors, administered intra-ventrally in animals submitted or not to astrocytic function blockade, and to the mild and unpredictable chronic stress model (ECBI). Therefore, male Wistar rats will be submitted or not to the IBSE model for 14 consecutive days and on the 15th. day injected intra-ventral hippocampus with microreactors or vehicle solution. A group of animals will also undergo blockage of astrocytic function. Five days after microinjections, the animals will be tested in the high-T and open-field maze models (animal models of anxiety and motor activity) and in the forced swim model (animal model of depression). Immediately after the behavioral tests, the animals will be euthanized and their brains processed for immunohistochemical verification of neurons and glial cells. An additional group of animals will be submitted to the evaluation of the electrophysiological activity of the ventral hippocampus, so that it is possible to better understand how chronic stress and treatment with microreactors interfere with the electrophysiology of the investigated structure.

Professor: Milena de Barros Viana

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