Dados do Trabalho

Título

EFFECT OF ADMINISTRATION OF DONEPEZIL, GALANTAMINE, MEMANTINE AND/OR FLUOXETINE IN ANIMAL MODEL OF DEPRESSION AND DEMENTIA

Introdução

Alzheimer's disease (AD) is characterized by cognitive decline, memory loss and also depression. Its pathophysiology is not fully elucidated, and new theories of its origin and development emerge. Inflammation in AD has been extensively investigated, as it may be key points for a better understanding of this dementia. Like AD, major depressive disorder (MDD) still has its pathophysiology under study, and its inflammatory theory is very similar to AD, indicating that, in addition to being one symptom, it may be a risk factor for AD.

Objetivo

the present study seeks to evaluate the levels of cytokines tumor necrosis factor alpha (TNF-α), interleukin (IL) -1ꞵ, IL-6 and IL-10 in frontal cortex and hippocampus of Wistar rats submitted to a chronic mild stress protocol (CMS) for induction of an animal model of depression and administration of intrahippocampal am-amyloid (ꞵA) oligomers for induction of the dementia model.

Método

60-day-old Wistar rats underwent the CMS protocol for 40 days. After the CMS, the animals were subjected to stereotaxic surgery for intrahippocampal administration of ꞵA or artificial cerebrospinal fluid (ACSF). The next day, the treatment starts with water, memantine, galantamine, donepezil and/or oral fluoxetine for 17 days. On the 59th day of the experimental protocol, euthanasia was performed, and the frontal cortex and hippocampus were dissected for subsequent dosages of the cytokines TNF-α, IL-1ꞵ, IL-6 and IL-10.

Resultados

The results of the study show that animals submitted to the ECM and administration of Aꞵ had increased levels of TNF-α and IL-1ꞵ in the frontal cortex and reduced IL-10 in the hippocampus. Fluoxetine reversed TNF-α and IL-1ꞵ levels in the frontal cortex. Furthermore, the association fluoxetine + donepezil reversed the reduction in IL-10 levels in the hippocampus. Galantamine, as well as its association with fluoxetine and an association of donepezil with fluoxetine, were also effective in reversing the levels of TNF-α in the cortex. Animals treated with memantine, as well as its association with fluoxetine, association of galantamine and fluoxetine and the association of donepezil with fluoxetine had advanced increased IL-10 levels in the frontal cortex. In hippocampus, only treatments with donepezil were able to increase the levels of IL-1ꞵ and IL-10.

Conclusão

The results indicate a pathophysiological interaction between the diseases, and the association of drugs may be a future therapeutic strategy to improve the patient's quality of life.

Palavras-chave

Alzheimer's Disease; Depression; Inflammation.