My PD Story

How Brain Chemical Imbalances Lead to Movement Problems

Mark Howe, PhD, of Boston University, received a Parkinson’s Foundation Stanley Fahn Junior Faculty Award to study the role of a brain chemical called acetylcholine in Parkinson’s disease (PD) movement problems. The findings will offer new insight into potential diagnostic markers and novel treatment strategies for correcting brain chemical imbalances that can lead to movement disorders in Parkinson’s.

“I have long been fascinated by how our nervous systems select and invigorate actions,” said Dr. Howe. “In Parkinson’s disease (and other basal ganglia disorders), the process of translating intention into smooth, vigorous action is profoundly and persistently affected. What are the electrical and chemical signals in the brain that determine whether or not we act, and how do they become compromised in disease? This is a central unresolved question that inspires research in my laboratory.”

In people with Parkinson’s, the cells that make the brain chemical dopamine — called midbrain dopaminergic neurons — are impaired. As Parkinson’s progresses, more dopamine-producing brain cells die. The brain eventually reaches a point where it stops producing dopamine in any significant amount. This causes increasing problems with movement. Motor function depends on the coordinated interaction of dopamine and acetylcholine.

“We are only beginning to unravel the consequences of dopamine loss on the brain dynamics controlling action in the intact, behaving brain,” said Dr. Howe. “Studies have pointed to interactions between dopamine and the neurotransmitter, acetylcholine, as being particularly important for proper movement invigoration and control.”

Dr. Howe will use a combination of imaging approaches in mouse models of Parkinson’s to investigate the links between the depletion of dopamine, the interplay of dopamine and acetylcholine, and the progressive emergence of Parkinson’s-related movement deficits.

Ultimately, this knowledge will be invaluable for diagnosing Parkinson’s at the earliest stages and developing the most effective and side-effect free treatments possible.

The results of Dr. Howe’s work may also give people with Parkinson’s and clinicians a deeper understanding of why current treatments work or don’t work, helping to adjust surgical and pharmacological interventions to improve quality of life.

Of his Parkinson’s Foundation grant, Dr. Howe said, “Myself and other lab personnel have been eager to apply our basic knowledge and tools to Parkinson’s disease research, but we have lacked the financial support to do so. We are thrilled that this award will give us the means to pursue a natural extension of our ongoing research.”