Lamotrigine Attenuates Lipopolysaccharide-Induced Working-Memory Impairment and Is Associated with Changes in...

Persistent neuroinflammation, oxidative imbalance, and neuronal apoptosis are key mechanisms underlying memory loss and working-memory impairment in many neurodegenerative conditions. LTG, an established anticonvulsant recognized for its glutamate-modulating and immune-dampening actions, has been reported to exert neuroprotective actions beyond seizure control. This study investigated whether LTG can counteract LPS-induced deficits in cognition and neuroinflammatory responses in rats by modulating oxidative stress- and apoptosis-related markers.

A total of twenty-four rats were allocated into four different groups: Control, LPS, LTG, and LTG + LPS. LTG (30 mg/kg, orally) was administered for 15 days, whereas LPS (1 mg/kg, intraperitoneally) was administered during the final four days to provoke neuroinflammation. Working memory abilities were assessed utilizing the Y-maze spontaneous alternation test. Subsequently, brain tissues were analyzed for inflammatory mediators (COX-2, TNF-α, IL-6), apoptotic markers (Caspase-3, Bcl-2, BAX), and oxidative stress indicators (MDA, GSH, catalase).

LPS exposure produced significant memory deterioration, accompanied by elevated COX-2, TNF-α, IL-6, and MDA levels, along with reduced GSH and catalase activity, indicating oxidative and inflammatory stress. BAX and Caspase-3 expression were markedly enhanced, whereas Bcl-2 expression was significantly reduced. Pretreatment with LTG markedly attenuated the LPS-induced decline in Y-maze performance, cytokine elevation, and alterations in redox and apoptotic parameters.

LTG effectively attenuated LPS-induced cognitive impairment and neuroinflammatory responses, accompanied by improvements in oxidative stress- and apoptosis-related markers. These findings support further investigation of the potential preventive or neuroprotective effects of LTG against neuroinflammation-associated working-memory impairment.