Lakshmi Hareendran was part of a research team investigating drug treatment for Parkinson’s, a neurodegenerative disorder caused by a loss of the brain chemical dopamine.

The dopamine circuit involved in motor movements consists of two receptors in the brain, the D1 and the D2 receptors. The current treatment for Parkinson’s is the drug L-DOPA, which acts on both of these receptors to release and replenish dopamine in the brain.

Hareendran and her colleagues in the Freshman Research Immersion program (FRI) at Binghamton provided evidence that stimulating the D2 receptor produces cognitive deficits, illustrating that L-DOPA may not be the best treatment for Parkinson’s.

The researchers treated rodents with L-DOPA and drugs that target either the D1 or the D2 receptors and then observed the effects on their ability to complete a behavioral task.

Stimulating the D2 receptor caused attention deficits on the behavioral tasks in both Parkinson’s and control models. Stimulating the D1 receptor produced no such effects.

“Parkinson’s disease is one of the most common neurodegenerative diseases in the world,” Hareendran says. “Knowing that the current treatment isn’t as effective as it could be is important.”

Hareendran, 21, has wanted to be a doctor since she was growing up on Long Island, influenced by several doctors in her family. Even then, she was interested in neuroscience.

“I had an uncle who was a brain surgeon,” Hareendran says. “As a kid, just thinking about him being able to understand something as complex as the human brain really inspired me to go down that path.”

Hareendran wants to work with Doctors Without Borders someday. An experience with MEDLIFE, an organization that provides medical care to impoverished areas, helped to solidify her goal. Hareendran traveled with the group to Peru and Ecuador to help set up medical clinics.

“My parents are refugees from Sri Lanka,” Hareendran says. “There was a genocide happening there for a while, so specifically with Doctors Without Borders I want to go and give back there.”

Hareendran is also president of the Indian International Student Union and was a peer mentor for FRI after she finished the program.

Corinne Kiessling, research educator for the FRI neuroscience stream, emphasized Hareendran’s dedication.

“She was one of those students that puts extra hours in, came in early, stayed late,” Kiessling says. “As a peer mentor, she was very open and receptive, and she challenged students to find answers. She’s a natural leader.”

Hareendran and her colleagues published their research in UCLA’s undergraduate research journal.

Joy Hallmark began conducting research in high school. Now, she studies treatments for Parkinson’s disease in a Binghamton University laboratory. 

Parkinson’s is treated with a compound called Levodopa, or “L-dopa,” which causes abnormal involuntary motions after prolonged use.

Hallmark works with Christopher Bishop, an associate professor of psychology, to test several compounds that may allow Parkinson’s to be treated without this side effect. They rely on an animal model, observing the effects different Parkinson’s treatments have on rats’ body movements.

“The thing that attracted me most about this research was the fact that it was translational, so what you do in the lab applies in the field,” says Hallmark, who plans to pursue a doctorate or go to medical school after graduation. “We take what we’re learning now, and we can apply it by making new drugs and helping people.”

For the past year, Hallmark has been researching two compounds to see how they would affect Parkinson’s patients. As a part of the Undergraduate Research Center’s Summer Scholars and Artists program, Hallmark completed an eight-week fellowship with a postdoctoral student studying the serotonin system and its relationship to Parkinson’s.

“I’ve always had an interest in neurodegenerative disorders, so it was cool to come here and find Dr. Bishop’s lab and be able to take my interest a step further,” Hallmark says.

When she was in high school, the Queens native studied Alzheimer’s disease for three years at the Albert Einstein College of Medicine as part of the Intel Science Talent Search program.

Hallmark’s “prolonged interest” in medicine began even before that, though. “From a young age, I always wanted to be challenged,” she says. “I used to sit in the medical section at Barnes & Noble and just read the medical dictionary and learn new terms that I didn’t know.”

Bishop says Hallmark seemed like a great fit for his lab when they first met, and her work since has been “a testament to that fit.”

“She has demonstrated a commitment and growing knowledge base that has made her not only increasingly autonomous, but a true asset,” Bishop says. “Joy has proven herself to be an excellent young scientist, and her trajectory is outstanding.”

Hallmark says her passion for studying neuroscience stems from her curiosity and her willingness to explore uncharted territories. “The brain, I think, is just so intricate and there are so many things that we have yet to know about it,” she says. “I love going into the unknown and trying to figure things out.”

Christopher Bishop, assistant professor of psychology, said his primary interest lies not only in the treatment of Parkinson’s but also in the side effects of treatment.

“Parkinson’s disease patients have trouble with movement,” Bishop said. “They move more slowly. They have rigidity in their limbs. They have balance problems and tremors.”

Those cardinal symptoms are a result of a deficit of dopamine in the brain.
Dopamine is a neurotransmitter that’s essential for movement; it also plays an important role in behavior, cognition and sleep.

In Parkinson’s patients, neurons in the brain that make dopamine die. Scientists still aren’t sure why; genetic factors are believed to play only a small role.

This deficit of dopamine can be reversed with treatment using a compound called L-DOPA, which has been the gold standard in Parkinson’s treatment for about 50 years.

The brain converts L-DOPA into dopamine, which is why it’s an effective replacement therapy for patients. For five to 10 years, this treatment works well. “The problem,” Bishop explained, “is that Parkinson’s is a progressive disease. You lose more and more of these neurons as time goes on, so therapeutically, doses of L-DOPA must increase.”

While that works for some people, many patients suffer troubling side effects as the dosage increases.

“By year 10,” Bishop said, “as many as 90 percent of patients will start to suffer from motor fluctuations and something called L-DOPA-induced dyskinesia. So you go from a state of no treatment where you’re not moving well, to a state where the drug is working well and you’re moving fluidly, to a point where L-DOPA doses are very high and you’re producing these abnormal, involuntary movements.”

Think of the actor Michael J. Fox’s recent television appearances. The excessive movements he displays aren’t a result of his Parkinson’s disease, but rather a symptom of the chronic L-DOPA he’s had.

And patients can’t simply stop taking L-DOPA; if they do, they face a nearly “frozen” life with incredibly limited ability to move.

This situation is an increasingly urgent medical concern. Roughly 1 million people in the United States have Parkinson’s; 50,000 more Americans are diagnosed with the disease each year. “That’s only going to increase as our population ages,” Bishop said. “This is not something that’s going away.”

Gerald Sonnenfeld, vice president for research, noted the University is delighted with Bishop’s receipt of funding from the National Institutes of Health. “His research on Parkinson’s disease is in the forefront of current worldwide efforts, and this has been supported by his receipt of this grant,” Sonnenfeld said. “We wish him great success on his efforts to understand Parkinson’s disease treatments and side effects.”

Bishop and his colleagues at Wayne State University’s medical school and the Veterans Administration hospital in Chicago hope to find a way to reduce dyskinesia and suppress these movements. There are very few treatments available, in part because how dyskinesia develops is still a mystery.

“We are beginning to believe that dyskinesia is actually the inability to suppress motor memories as a result of the drug’s stimulation,” Bishop said.

One possible treatment relates to glutamate, a neurotransmitter in the brain that can play a role in these memory processes, helping to lay down new pathways for motor memories.

The five-year grant from the National Institute for Neurological Disorders and Stroke will allow Bishop and his team to study serotonin compounds that reduce glutamate following L-DOPA treatment. Bishop’s work has also been supported by the American Parkinson’s Disease Association.
Bishop hopes to find out how these compounds work and what they’re doing that can help scientists understand what dyskinesia really is.

Bishop has developed a way to look at dyskinesia as it’s occurring and measure glutamate levels in different parts of the brain. Early experimentation has supported his theories, showing a reduction in dyskinesia as the serotonin compound is administered.

“I was drawn to this field,” Bishop said, “because not only am I asking, ‘How does it work?’ but also ‘How does it help with treatment?’ I think that has been a motivation for me.”