methyl-jasmonate and Memory-Disorders

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 50 mg/kg) 30 min before exposure to UCMS daily for 28 days. Memory function was 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.

Topics: Acetates; Animals; Antioxidants; Biogenic Monoamines; Brain; Cyclopentanes; Dose-Response Relationship, Drug; Gene Expression; Male; Memory Disorders; NF-E2-Related Factor 2; Oxylipins; Plant Growth Regulators; Rats; Rats, Wistar; Stress, Psychological; Synaptic Transmission

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.

Topics: Acetates; Amyloid beta-Peptides; Animals; Anti-Inflammatory Agents; Astrocytes; Biomarkers; Brain; Cyclooxygenase 2; Cyclopentanes; Inflammation; Interleukin-1beta; Lipopolysaccharides; Male; Maze Learning; Memory; Memory Disorders; Mice; Microglia; Neuroimmunomodulation; NF-kappa B; Nitric Oxide Synthase Type II; Oxylipins; Prefrontal Cortex; Tumor Necrosis Factor-alpha

Psychosis is a chronic neuropsychiatric disorder that affects millions of individuals worldwide and impairs the quality of life and productivity of the patients. The clinical efficacy of antipsychotic drugs has been compromised by adverse effects, relapse, and therapeutic failures, thus necessitating search for alternative agents. Methyl jasmonate (MJ) is a bioactive compound reported to have beneficial effects in various neurological disorders. This study was undertaken to investigate the antipsychotic-like effects of MJ in mice. Male Swiss mice were pretreated intraperitoneally with MJ (25-100 mg/kg) or vehicle (10 mL/kg) 60 min prior to bromocriptine (5 mg/kg) or acute injection of ketamine (10 mg/kg). Thereafter, each mouse was observed for stereotype behaviors for 2 min at 10, 15, 20, 30, and 45 min post-bromocriptine injection. Another set of mice received MJ (25-100 mg/kg) or vehicle (10 mL/kg) 60 min after chronic ketamine injection (20 mg/kg, i.p) once daily for 14 consecutive days. Afterwards, locomotor activity and memory function in this sequence were evaluated using open field and Y-maze tests. The levels of malondialdehyde (MDA) and glutathione (GSH) and activity of catalase and superoxide dismutase (SOD) in the brain were determined. MJ significantly inhibited stereotypy behavior induced by bromocriptine or acute ketamine injection, which suggest antipsychotic-like activity. It also attenuated hyper-locomotion and memory deficits induced by chronic injection of ketamine in mice. The increased oxidative stress as shown by the altered brain levels of MDA, GSH, and activity of antioxidant enzymes induced by chronic injection of ketamine was reduced by MJ. Taken together, these findings suggest that MJ demonstrated antipsychotic-like property via mechanism related to its antioxidant property and interference with dopaminergic neurotransmission.

Topics: Acetates; Animals; Antioxidants; Antipsychotic Agents; Brain; Bromocriptine; Cyclopentanes; Disease Models, Animal; Dopamine; Dose-Response Relationship, Drug; Ketamine; Locomotion; Male; Maze Learning; Memory; Memory Disorders; Mice; Oxidative Stress; Oxylipins; Psychotic Disorders; Stereotyped Behavior; Time Factors

This present study was carried out to investigate the likely mechanisms by which methyl jasmonate (MJ), 'an agent widely used in aromatherapy for neurological disorders, attenuates lipopolysaccharide (LPS)-induced memory deficits in mice. Mice were given intraperitoneal administration of LPS (250 µg/kg) alone or in combination with MJ (10-40 mg/kg), donepezil, DP (1 mg/kg), or vehicle for 7 successive days. Thereafter, memory was assessed using object recognition test (ORT). Acetylcholinesterase and myeloperoxidase activities were estimated in brain tissue homogenates. Brain levels of nitric oxide and markers of oxidative stress as well as histopathologic changes of the prefrontal cortex and cornu ammonis 1 (CA1) of the hippocampal region were also assessed. MJ (10-40 mg/kg) attenuated LPS-induced memory impairment in ORT. Moreover, the increased brain activities of acetylcholinesterase and myeloperoxidase enzymes were suppressed by MJ when compared with control (p < 0.05). Increased brain oxidative stress and nitric oxide levels in LPS-treated mice were significantly decreased by MJ. It offers protection against LPS-induced neuronal degeneration of the prefrontal cortex and CA1 of the hippocampus, suggesting neuroprotective effect. Taken together, these findings showed that MJ offers protection against LPS-induced memory deficits via mechanisms related to inhibition of acetylcholinesterase, myeloperoxidase, oxidative stress and neuronal degeneration.

Topics: Acetates; Acetylcholinesterase; Animals; Brain; Cyclopentanes; Lipopolysaccharides; Memory Disorders; Mice; Neuroprotective Agents; Nitrites; Oxidative Stress; Oxylipins; Recognition, Psychology