Gallic acid attenuates lipopolysaccharide - induced memory deficits, neurochemical changes, and peripheral alterations in purinergic signaling

Abstract

Neuroinflammation is associated with many neurological disorders. Gallic acid (GA) has attracted significant attention due to its biological properties, such as neuroprotective, anti-inflammatory, and antioxidant effects. In this study, we evaluated the effects of GA in memory, TNF-α levels, oxidative stress, and activities of acetylcholinesterase (AChE), Na⁺, K⁺-ATPase and Ca²⁺-ATPase in the brain of mice exposed to lipopolysaccharide (LPS). Additionally, we evaluated alterations in adenine nucleotides and nucleosides in the serum. Male mice were orally pretreated with vehicle or GA (50 or 100 mg/kg) for 14 days. Between days 8 and 14, the animals also received LPS injection (250 µg/kg) or saline. At the end of the experimental protocol, the animals were submitted to object recognition test, euthanized and cerebral cortex, hippocampus, striatum and blood were collected. LPS induced memory deficits, which were prevented by GA treatment. GA protected against LPS-induced oxidative damage in the cerebral cortex, hippocampus and striatum by reducing reactive oxygen species and nitrite levels, while increasing total thiol content and activities of antioxidant enzymes. GA also prevented LPS-induced alterations in AChE, Na⁺, K⁺-ATPase, and Ca²⁺-ATPase activities in brain structures. LPS elevated TNF-α levels in the hippocampus and cerebral cortex, which were attenuated by GA treatment. Furthermore, LPS caused a reduction in ADP and AMP hydrolysis and an increase in adenosine deamination in the serum, which were also prevented by GA. The effects of GA against neuroinflammation may be attributed to its potent antioxidant and anti-inflammatory properties, which modulate various pathways, including those involved in memory mechanisms.

Keywords: Gallic acid; Lipopolysaccharide; Mice; Neuroinflammation; Oxidative stress.