Antioxidant Diapocynin Prevents Parkinson’s Disease Motor Symptoms In Mice
A new study on a mouse model of Parkinson's disease suggests that a synthetic antioxidant molecule called diapocynin may be a viable preventative measure against the progression of motor symptoms.
As many as 1.5 million Americans live with Parkinson's disease, and while treatments like deep brain stimulation and certain drugs can ease symptoms, there is currently no cure.
The progressive neurodegenerative disorder involves the breakdown of communication between motor neurons in the nervous system, leading to tremors, deficits in motor coordination, and impaired balance.
That breakdown is caused by the death of neurons that produce the neurotransmitter chemical dopamine, which researchers believe is caused by increased oxidative stress in cells. As byproducts of oxidative stress, called reactive oxygen/nitrogen species (ROS or RNS), build up in neurons, they eventually create an environment too toxic for normal cell functions.
Diapocynin may offer protection against the usual symptoms for people with Parkinson's disease, according to researchers from the Medical College of Wisconsin (MCW) and Iowa State University.
The researchers found that the antioxidant, derived from the natural organic compound apocynin, prevented the usual motor coordination deficits of Parkinson's disease in a mouse model of the condition.
Preventing Parkinsonian Symptoms in Mice
Led by Dr. Balaraman Kalyanaraman, director of the MCW Free Radical Research Center, and postdoctoral fellow Dr. Brian Dranka, the researchers decided to investigate whether inhibiting the production of these reactive species in neurons could prevent Parkinson's disease symptoms in a group of transgenic mice.
The genetically engineered mice used in the study were of a variety called LRRK2R1441G, which overexpresses a certain protein that typically leads the mice to develop Parkinsonian symptoms like loss of coordinated movements by 10 months of age.
Starting when the transgenic mice were 12 weeks old, the team orally administered diapocynin to them three times a week.
When the mice reached 16 months of age, the researchers put them through a series of motor coordination tests, like navigating to the base of a pole and across a rotating horizontal bar. They also measured how much distance the mice covered in an open space in 20 minutes, and painted their paws in different colors so they could analyze their gait patterns as they scurried through a narrow channel.
The results showed that compared to a group that was dosed with saline instead of the antioxidant, the transgenic mice given diapocynin performed better on the motor coordination tests — about as well, in fact, as normal mice without the Parkinsonian mutation.
However, inspecting the mouse brains revealed no significant differences in the health of dopaminergic neurons between normal mice and those with the Parkinsonian mutation.
"These early findings are encouraging, but in this model, we still do not know how this molecule exerts neuroprotective action," said Kalyanaraman in a news release.
It's unclear how the findings will translate to humans, but in future studies, the researchers hope to figure out the exact molecular mechanisms by which antioxidants like diapocynin protect neurons from degeneration.
They expect that further investigation of the LRRK2R1441G mice will lead to biological markers of Parkinson's disease that allow for early disease detection, which can enhance patients' quality of life by leaving enough time to take preventative measures against progressive motor deterioration.
Source: Dranka BP, Gifford A, Ghosh A, et al. Diapocynin prevents early Parkinson's disease symptoms in the leucine-rich repeat kinase 2 (LRRK2R1441G) transgenic mouse. Neuroscience Letters. 2013.