Neuroprotective potential of safinamide against LPS-induced neuroinflammation and cognitive dysfunction in mice.

Abstract

Neuroinflammation, a key pathological hallmark of neurological diseases, contributes to neurodegeneration, synaptic dysfunction, and cognitive decline. Safinamide shows toll-like receptor-mediated anti-inflammatory effects in cellular models; however, it's in vivo neuroprotective and neuroinflammatory effects remain unexplored. In the present investigation, the anti-neuroinflammatory impact of safinamide was evaluated in lipopolysaccharide (LPS)-induced mice using behavioral, biochemical, and histopathological assessments. LPS was administered intraperitoneally from days 8 to 15 to induce neuroinflammation, followed by 15 days of safinamide treatment at 10 mg/kg and 20 mg/kg. Safinamide 20 mg/kg significantly improved spatial and recognition memory, as evidenced by the percentage alternation in the Y-maze and recognition index in the novel object recognition test. Furthermore, safinamide significantly reduced the levels of Toll-like receptor 4 (TLR4), phosphorylated NF-κB (p-NF-κB), NLRP3, TNF-α, IL-6, IL-1β, acetylcholinesterase (AChE), and malondialdehyde (MDA), and increased levels of glutathione (GSH), catalase, and superoxide dismutase (SOD). Histopathological analysis revealed decreased amyloid-β deposition and preservation of neuronal architecture. These findings suggest that safinamide modulates neuroinflammatory and oxidative stress pathways and exhibits promising neuroprotective potential against inflammation-associated cognitive impairment.