Avaliação do perfil comportamental em um modelo animal da doença de Alzheimer tratado com gedunina

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease, accounting for most cases of dementia. It is characterized by the accumulation of β-amyloid peptide (Aβ) plaques and neurofibrillary tangles, triggering neuronal death, increased inflammatory response, and progressive memory loss responses. The general objective was to verify whether gedunin has the ability to mitigate the cognitive deficits observed in an experimental model through intracerebroventricular infusion of Aβ in Swiss mice. As specific objectives: 1) Evaluate whether the experimental model causes behavioral changes observed through cognitive decline and reduction in learning and memory; 2) Evaluate the effects of gedunin through behavioral tests in mice subjected to the Alzheimer's disease model. Seventy male Swiss mice were used, bred and maintained in the Neurophysiology Laboratory, on a 12h/12h light/dark cycle. The body mass of all animals was evaluated throughout the project. The animals were divided into control vehicle (CNTVEH), surgical control vehicle (HEPESVEH), β-amyloid vehicle (AβVEH), β-amyloid gedunin (AβGED) and β-amyloid gedunin with withdrawal on the day of behavioral tests (AβGEDRET). The induction of the experimental model was carried out at PN90 (post-birth), through intracerebroventricular Aβ infusion surgery. The animals underwent implantation of an osmotic minipump (duration period of 28 days), containing Aβ peptide solution or vehicle solution. The treatment, administered via gavage and on alternate days, began at PN90 continuing until PN134 (5mg/kg/day, diluted in 2.5% DMSO and corn oil – vehicle solution). After the infusion period of the osmotic minipump (PN118), the animals were subjected to behavioral tests: Passive Avoidance (EP; PN122–PN123), Open Field (CA; PN124), Object Recognition (RO; PN125–PN126), Puzzle Box (PB; PN127–PN129) and Barnes Maze (LB; PN130–PN133). The CNTVEH and HEPESVEH groups were consolidated into the Control group and the AβGED and AβGEDRET groups were consolidated into the Gedunin group when there were no behavioral differences between the pairs of indicated groups. We observed that animals that received Aβ infusion treated with vehicle showed memory and learning deficiencies in the RO and PB tests. In EP, an increase in the latency for descending the platform was observed in the Gedunin group when compared to the Aβ and Control groups. In CA, no differences in locomotor activity and anxiety-like behavior were observed between groups. In RO, the Aβ group showed a reduction in preference for the new object when compared to the Control and Gedunin groups. In PB, both animals in the Aβ and Gedunin groups showed an increase in latencies compared to those in the Control group. In LB, the latency to find target was increased in the Gedunin groups when compared to the Control and Aβ groups. The deficiencies presented by animals treated with gedunin, despite the results in which improved performance was observed, indicate that the use of this substance, at the moment, is more appropriate for understanding the mechanisms involved in cognitive deficits in animal models, and not for use in the clinic.