Methyl jasmonate ameliorates rotenone-induced motor deficits in rats through its neuroprotective activity and increased expression of tyrosine hydroxylase immunopositive cells.

Abstract

Decreased tyrosine hydroxylase (TH) activity, due to degeneration of dopaminergic neurons contributes to the low dopamine content and the motor deficits that characterized Parkinson's disease (PD). This study examines the effect of methyl jasmonate (MJ), a neuroprotective bioactive compound isolated from jasminum grandiflorum, on motor functions, immunopositive cells of TH, dendritic neurons and dopamine contents in rotenone (Rot)-treated rats. Rats pretreated daily with MJ (100mg/kg, i.p) for 21days also received Rot (2.5mg/kg, i.p.) 30min after each pretreatment for every 48h for 21days. Motor functions were assessed on day 22. The specific brain regions of the rats were processed for determination of dopamine contents, immunopositive cells of TH, neuronal cell morphology and dendritic aborizations. Rot impaired locomotion and rearing behavior, and decreased dopamine content in the striatum, prefrontal cortex and midbrain. It further reduced the expression of TH in the substantia nigra and striatum relative to vehicle-control (p < 0.05). Histopathologic studies revealed that Rot-treated rats had degenerated neurons with pyknotic nuclei and loss of nigrostriatal neuronal cells. Rot also altered the nigrostriatal dendritic neuronal networks, decreased the dendritic length and spine density. However, pretreatment with MJ improved motor deficits, increased TH activity and dopamine contents in the specific brain regions of Rot-treated rats. MJ also attenuated the cyto-architectural distortions, loss of neuronal cells and dendritic aborizations of the striatum of Rot-treated rats. These findings suggest that MJ may reverse the motor deficits associated with PD by modifying the key pathological abnormalities involved in the disease progression.