Efeito do composto 2-(4-(metiltio)fenil)-3-(3-(piperidin-1-il)propil)tiazolidin-4- ona na memória e em parâmetros bioquímicos cerebrais e sistêmicos em um modelo de demência esporádica do tipo Alzheimer

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease characterized by a decline in memory and cognitive functions. It is the most common form of dementia, with a progressive and irreversible character, affecting basic daily activities in patients. AD has become a major public health problem. Among the neurochemical mechanisms associated with AD are oxidative stress and alterations in signaling mediated by cholinergic synapses. Cholinergic neurotransmission being is main therapeutic target of the available treatments for AD. The therapeutic arsenal currently available is only possible to alleviate the symptoms of this disease, being unable to prevent its progression. Therefore, the research for new therapeutic alternatives capable of preventing or delaying the progress of AD becomes increasingly relevant, in order to provide a better quality of life for patients. Thiazolidin-4-ones are compounds that have been the target of research because these compounds have pharmacological activities such as antioxidant and anticholinesterase effects. Thus, the aim of the present study was investigated the effects of the compound 2-(4-(methylthio)phenyl)-3-(3-(piperidin 1-yl)propyl)thiazolidin-4-one (DS12) on memory and neurochemical parameters in an experimental model for AD induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) in rats. Adult male rats were divided into five groups: I- control (saline); II - DS12 (10 mg/kg); III-STZ, IV-STZ + DS12 (10 mg/kg); V-STZ + donepezil (5 mg/kg). The treatments were performed orally for 20 days. Behavioral parameters related to memory were evaluated through object recognition and Y-maze tests. After euthanasia, the cerebral cortex, hippocampus, and cerebellum were collected to evaluate markers of oxidative stress and acetylcholinesterase (AChE) enzyme activity. Biochemical and hematological parameters were evaluated in blood and serum samples. The results showed that memory impairment and the increase in AChE activity induced by STZ were prevented by treatment with DS12 and donepezil. STZ also increased the reactive oxygen species levels and a decreased catalase activity in hippocampus, cerebral cortex, and cerebellum. Treatment with DS12 was capable to protect against these oxidative changes in all brain structures. No changes were observed in serum biochemical parameters and hematological analyses. Treatment with DS12 was able to improve memory and neurochemical changes in an AD model without inducing toxic effects, suggesting the promising therapeutic potential of this compound.