Methyl jasmonate reverses chronic stress-induced memory dysfunctions through modulation of monoaminergic neurotransmission, antioxidant defense system, and Nrf2 expressions.

Abstract

Unpredictable chronic mild stress (UCMS) has been shown to cause memory loss via increased oxidative stress and deregulation of monoaminergic and cholinergic neurotransmissions. Although the benefits of methyl jasmonate (MJ), a well-known anti-stress plant hormone against chronic stress-induced psychopathologies, have been earlier reported, its effects on antioxidant defense molecules, monoaminergic transmitters, and nuclear factor erythroid 2-related factor 2 (Nrf2) immunopositive cells have not been extensively studied. The present study was designed to examine its effect on memory functions, antioxidant biomarkers, monoaminergic transmitters, and Nrf2 immunopositive cell expression in rats exposed to UCMS. Rats received an intraperitoneal injection of MJ (10, 25, and 50mg/kg) 30min before exposure to UCMS daily for 28days. Memory functionwas assessed on day 29 using a modified elevated plus maze and novel object recognition tests. The antioxidant biomarkers, level of monoamines (serotonin, noradrenaline, and dopamine), and Nrf2 immunopositive cell expression were determined in the rat brain tissues. The activity of cholinesterase and monoamine oxidase enzymes was also determined. MJ attenuated memory deficits and elevated the brain levels of monoamines in UCMS rats. UCMS-induced increase of brain cholinesterase and monoamine oxidase activities was inhibited by MJ. Also, MJ attenuated UCMS-induced decrease in antioxidant enzymes (CAT, GPx, GST, and SOD) and thiol contents in the brains of rats. UCMS-induced increase in NO level and Nrf2 immunopositive cell expression in the rat's brain was attenuated by MJ. Taken together, these findings suggest that increasing antioxidant defense molecules and monoaminergic/cholinergic neurotransmitters and decreasing the Nrf2 immunopositive cell expressions may contribute to the memory-promoting effects of MJ in rats exposed to UCMS.