Methyl jasmonate attenuates memory dysfunction and decreases brain levels of biomarkers of neuroinflammation induced by lipopolysaccharide in mice.

Neuroinflammation plays a central role in the etiology and progression of Alzheimer's disease (AD), a neurodegenerative disorder, characterized by a gradual loss of memory functions. Thus, it has been proposed that agents that could reduce inflammatory processes in AD brains might be useful for the treatment of the disease. Methyl jasmonate (MJ) is a bioactive compound, which has been reported to exhibit anti-amnesic and in vitro anti-inflammatory activities. In this study, we further examine its effects on the brain levels of biomarkers of neuroinflammation in lipopolysaccharide (LPS)-induced memory deficits in mice. Mice (n=6) were pretreated intraperitoneally with MJ (10-40mg/kg), donepezil (DP) (1mg/kg) or vehicle (10mL/kg) for 30min prior to injection of LPS (250μg/kg, i.p) daily for 7days. Thirty minutes after LPS administration on day 7, memory function was assessed using Y-maze test. After Y-maze test, the levels of biomarkers of neuroinflammation: prostaglandin E2 (PGE2), tumor necrosis factor α (TNFα) and interleukin 1β (IL1β) were estimated in brain tissue homogenates using ELISA. Expressions of positive cells of cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), nuclear factor kappa B (NF-κB) and amyloid-beta (Aβ) in the prefrontal cortex were also assessed using immunohistochemistry technique. Our data showed that MJ (10, 20 and 40mg/kg) significantly (p<0.05) reversed LPS-induced memory deficits in mice. The increased brain levels of PGE2, TNFα and IL1β in LPS-treated mice were significantly (p<0.05) reduced by MJ indicating anti-neuroinflammatory activity. MJ also suppressed the expression of COX2, iNOS and NFκB, which further suggest anti-neuroinflammation. The increased brain level of Aβ in LPS-treated mice was significantly (p<0.05) suppressed by MJ suggesting anti-amyloidogenesis-like effect. Our present data showed that MJ attenuated LPS-induced memory dysfunction via mechanisms involving inhibition of pro-inflammatory mediators and beta-amyloid generation in mice.