Neuroprotective effects of a thiazolidin-4-one against lipopolysaccharide-induced neuroinflammation in mice: impact on memory, antioxidant and cholinergic systems, and glial reactivity.

Neuroinflammation is a defense mechanism of the central nervous system triggered by tissue injury and involves astrocytes and microglia. Upon activation, both release cytokines and reactive species, contributing to the inflammatory response. The cholinergic system, known for its role in neurotransmission, also plays an anti-inflammatory role, mediated by acetylcholine (ACh). In this context, compounds capable of modulating neuroinflammation are vital for developing therapeutic strategies to mitigate neurodegenerative diseases and promote brain health. Thiazolidinones have emerged as promising candidates, owing to their antioxidant, anti-inflammatory, and anticholinesterase properties. The aim of this study was to evaluate the effects of 2-(4-(methylthio)phenyl)-3-(3-(piperidin-1-yl)propyl)thiazolidin-4-one (DS12) on lipopolysaccharide (LPS)-induced neuroinflammation in mice. Adult male Swiss mice were divided into groups: I) Control, II) LPS (250 μg/kg), III) LPS (250 μg/kg) plus DS12 (5 mg/kg), and IV) LPS (250 μg/kg) plus DS12 (10 mg/kg). Mice received LPS and DS12 for seven consecutive days. Food consumption, body weight, locomotion, memory, cholinergic function, oxidative stress parameters, glial reactivity, and cytokine levels were assessed. LPS reduced food intake and weight gain, memory deficits, and increased oxidative damage in the cerebral cortex, striatum, and hippocampus. Additionally, LPS increased acetylcholinesterase activity and M1mACh receptor expression, as well as markers of glial reactivity and cytokine levels in the hippocampus. Treatment with DS12 effectively mitigated these alterations induced by LPS. In conclusion, DS12 shows potential in protecting against neuroinflammation, supporting its use as a promising candidate for therapeutic strategies targeting neurodegenerative diseases.