PROMISING ACTION OF 7-CHLORO-4-PHENYLSELANYL QUINOLINE (4-PSQ) FOR DEPRESSION AND ALZHEIMER'S DISEASE (Atena Editora)

Abstract

Alzheimer's disease (AD) is the leading and most common cause of senile dementia, accounting for 50-75% of diagnosed cases. In developed countries, AD is the fourth leading cause of death, second only to cardiovascular disease, cancer and stroke. Oxidative stress plays a central role in the initiation and progression of AD due to its high rate of oxygen utilization; high content of polyunsaturated lipids that are susceptible to lipid peroxidation; and poor concentrations of antioxidants. Histologically, the presence of hyperphosphorylated tau protein, amyloid β peptide aggregates, reduction of synaptic density, activation of glial cells and neuronal loss, including nervous cells of the cholinergic system, in which neurotransmission is related to learning processes and consolidation of memory, is evidenced. memory. Studies suggest that amyloid beta plaques cause cognitive damage by interrupting synaptic function leading to an underregulation of these networks and compromising anatomically and functionally interconnected brain areas. Depression is an important comorbidity of AD, being the most frequent neuropsychiatric complication in this disease, affecting approximately 50% of patients. Heterocyclic compounds have shown importance in the construction of new drugs, among which quinoline and its derivatives stand out through different mechanisms of action, such as inhibitors of cell cycle growth and apoptosis. Given the above, the present study aimed to investigate the involvement of cell signaling molecules and the cholinergic and monoaminergic systems in an experimental model of depression and AD using the amnesia method induced by the injection of scopolamine bromide - a non-selective cholinergic antagonist of muscarinic receptors. Therefore, the therapeutic activity of a quinoline derivative, 4-PSQ, was evaluated in oxidative stress parameters such as oxygen levels (ERO); thiobarbituric acid reactive substances (TBARS); activity of catalase enzymes (CAT); superoxide dismutase (SOD) as well as the activity of the enzyme glutathione peroxidase (GPx) in the cerebral cortex and hippocampus. Based on evidence, we conclude that the effects of 4-PSQ may be associated with attenuation of HPA axis activation, attenuation of changes in the monoaminergic system, modulation of oxidative stress, restoration of AChE activity and reduction of neuroinflammation.