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The interface between depression induced by chronic moderate stress, the intensification of Parkinson's Disease and its inflamatory aspects.

Grant number: 22/07426-2
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): November 01, 2022
Effective date (End): October 31, 2023
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal Investigator:Ariadiny de Lima Caetano
Grantee:Sophia Ohf Campos
Host Institution: Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP). Fundação Arnaldo Vieira de Carvalho. São Paulo , SP, Brazil

Abstract

Depression is a disease characterized by loss of interest and pleasure in various activities and is present in about 5% of adults. One of its causes seems to be stress, which is related to an exacerbated secretion of glucocorticoids and increased oxidative stress. Furthermore, when this stress is present early in life, it has the potential to leave long-term scars on the individual. This consequently can generate greater vulnerability to the development of metabolic, neuropsychiatric and neurodegenerative disorders.Parkinson's Disease (PD) is caused by the destruction of dopaminergic neurons in the nigrostriatal pathway and results in dopamine deficiency in substancia nigra. Unfortunately, it is only diagnosed at a more advanced stage, when body tremors are already occurring. However, as neurodegeneration already occurs years before these symptoms, it is very common for these individuals to present signs unrelated to PD, such as depression.Regarding the initial neurodegeneration, it is interesting to note that depression is present before the diagnosis of PD in 40 to 50% of cases. Even so, it is shocking that the biochemical correlation between the two diseases is poorly understood, mostly is based on microglial sensitization. This sensitization, which activates an inflammatory cascade that generates neuronal damage, is present in aging, which is the time when PD is diagnosed.However, with the large presence of neuropsychiatric symptoms years before the diagnosis of PD, it is clear that depression may contribute and give the neuro-inflammatory conditions for the loss of dopaminergic neurons to occur. In addition, as 95% of PD cases are caused by the environment, and as the population ages further, causing even more PD cases to be expected, it is essential to understand how stress participates in brain neurodegeneration. Thus, understanding how early-life stress is related to the synthesis of dopamine in the substantia nigra in adulthood could elucidate possible risk groups for PD and contribute to the fight against the disease.

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