3-(3-(diethylamino)propyl)-2-(4-(methylthio)phenyl)thiazolidin-4-one Attenuates Scopolamine-induced Cognitive Impairment in Rats: Insights Into Neuroprotective Effects.

Journal: Molecular Neurobiology
Published:
Abstract

Alzheimer's Disease (AD) is characterized by memory decline, dysregulation in cholinergic and purinergic signaling, neuroinflammation, and oxidative stress. Current treatments are limited, highlighting the need for new compounds to prevent or delay AD progression. Thiazolidinones have emerged as promising candidates due to their antioxidant, anti-inflammatory, and anticholinesterase properties. The aim of this study was to evaluate the effects of 3-(3-(diethylamino)propyl)-2-(4-(methylthio)phenyl)thiazolidin-4-one (DS27) in a rat model of scopolamine-induced memory deficits. Male rats were divided into groups: I - Control, II - Scopolamine (SCO) (1 mg/kg), III - SCO and DS27 (5 mg/kg), IV - SCO and DS27 (10 mg/kg), V - SCO and donepezil (5 mg/kg). The animals were treated orally with DS27 or donepezil for seven days. On the 8th day, they underwent the open field test and inhibitory avoidance training, followed by intraperitoneal administration SCO. Twenty-four hours later, an inhibitory avoidance test was conducted. Acetylcholinesterase (AChE) activity, oxidative stress, and inflammatory and purinergic parameters were analyzed in the cerebral cortex, hippocampus, cerebrospinal fluid, serum, lymphocytes, and liver. DS27 prevented memory deficits, alterations in AChE activity, and oxidative damage induced by SCO in brain structures. Additionally, DS27 prevented SCO-induced decrease in IL-10 levels, and increase in IL-6, and TNF-α expression in the cerebral cortex, and normalized ATP and ADP hydrolysis in cerebrospinal fluid and lymphocytes. DS27 did not induce oxidative stress in the liver or alter serum biochemical parameters. These findings suggest that DS27 has significant neuroprotective properties and could be a promising alternative for treating neurodegenerative diseases like AD.

Authors
Anita De Souza, Kelen Cristiane Goularte, Raphaela Piccoli, Solange Custódio, Julia De Mello, Melinda Victor, William Domingues, Lucas De Souza, Laís Dos Santos Gonçalves, Vinicius Campos, Wilson Cunico, Jean Oses, Francieli Stefanello, Mayara Sandrielly De Aguiar, Roselia Spanevello