Rodent Study Reveals Anti-inflammatory Effects of Mirapex
Mirapex (pramipexole), an approved medication to treat motor symptoms in Parkinson’s disease, reduced levels of immune proteins in the brain that are associated with inflammation, a rat model study reveals.
The study, “Effect of Pramipexole on Inflammatory Response in Central Nervous System of Parkinson’s Disease Rat Model,” was published in the journal Archives of Medical Research.
The underlying cause of Parkinson’s disease is the loss of brain cells (neurons) that produce dopamine, a signaling molecule needed to control body movements. Damage to dopamine-producing cells — called dopaminergic neurons — occurs due to the clumping of misfolded alpha-synuclein protein.
Studies suggest the immune system attacks damaged dopaminergic neurons, with immune cells releasing inflammatory signaling proteins (cytokines) to regulate the immune response.
The presence of these cytokines in the brain and spinal cord (central nervous system, CNS) have been associated with Parkinson’s progression and motor symptoms, but whether the inflammatory process causes further loss of dopaminergic neurons is unclear.
Mirapex is an oral medication designed to relieve some of the motor symptoms of Parkinson’s by mimicking the action of dopamine and fulfilling
some of its functions in the brain. Although Mirapex can effectively reduce motor symptoms, there is evidence it also has anti-inflammatory effects.
To further investigate Mirapex’s anti-inflammatory properties, researchers at the Xinjiang Medical University in China treated rats with Mirapex after inducing inflammation in the substantia nigra, the area of the brain where dopaminergic neurons are located. The substantia nigra also is where dopaminergic nerve loss often begins and is particularly affected in Parkinson’s.
“In this study, we treated the animal models with [Mirapex], compared inflammatory factors in substantia nigra … between groups to clarify the drug’s effect on the central inflammatory response,” the team wrote.
Lipopolysaccharide (LPS) was injected into the substantia nigra of rat brains, stimulating the inflammatory response and leading to the loss of dopaminergic neurons and characteristic Parkinson’s symptoms. Rats were divided into two groups, with one receiving Mirapex and the other a blank control. Rats not exposed to LPS served as healthy controls.
To first evaluate motor impairment, rats were subjected to the apomorphine (APO)-rotation test, used to evaluate motor impairment. After 14 days, rats treated with Mirapex showed significantly improved motor function.
To investigate inflammation, the activity of genes that carry instructions for two pro-inflammatory cytokine proteins — interleukin-6 (IL-6) and TNF-alpha — were measured in the substantia nigra.
Regardless of Mirapex treatment, the gene activity of IL-6 and TNF-alpha in Parkinson’s rats was significantly higher compared to healthy control rats. However, when compared to untreated Parkinson’s rats, Mirapex significantly decreased the gene activity of both IL-6 and TNF-alpha.
The concentrations of IL-6 and TNF-alpha proteins in the substantia nigra were consistent with their gene activity. The IL-6 level in healthy rats was 251.01 picograms per mL (pg/mL), whereas in Parkinson’s rats treated with Mirapex, IL-6 was 405.14 pg/mL compared to 618.42 (pg/mL) in untreated rats.
The TNF-alpha levels in healthy rats was 94.57 pg/mL. In Mirapex-treated Parkinson’s rats, TNF-alpha concentration was 143.30 pg/mL compared to 223.27 pg/mL without Mirapex, which “suggested inhibition of inflammation by [Mirapex],” the researchers wrote.
“Here, we demonstrated that [Mirapex] down-regulated [gene activity] of IL-6 and TNF-[alpha], decreasing the level of inflammatory factors in CNS of [Parkinson’s] model rats,” the authors wrote. “Additionally, the drug improved behavior of these rats.”
The researchers added that “new research regarding upstream pathway and effects on [the immune system] should be conducted.”