D. James Surmeier, PhD, the Nathan Smith Davis Professor and chair of Neuroscience, has been named the recipient of the 2023 Annemarie Opprecht Parkinson Award, an international award recognizing significant contributions to the field of Parkinson’s disease research.
Given by the Annemarie Opprecht Foundation, the award is presented once every three to six years to promote medical research around Parkinson’s and comes with a prize of 100,000 Swiss francs.
The award is presented in Zürich, Switzerland, during the Annual Joint Scientific Meeting of the Swiss Neurological Society and the Swiss Society for Behavioral Neurology.
Surmeier’s research centers on the mechanisms underlying Parkinson’s disease and employs a combination of electrophysiological, optical, genetic and behavioral approaches.
The study cited in his award, published in 2021 in Nature, demonstrates that loss of mitochondrial function in dopaminergic neurons is sufficient to cause Parkinson’s disease and challenges long-held views on the network origins of disease symptoms.
It’s understood that the death of dopamine-producing neurons that control the basal ganglia is responsible for the core motor symptoms of Parkinson’s disease, including slowness of movement and rigidity.
In the study, Surmeier and his collaborators discovered that damage to mitochondria — cellular power plants — in dopaminergic neurons caused progressive, human-like Parkinsonism in mice.
Investigators found that damage to mitochondria resulting in the disruption of mitochondrial complex I, a key enzyme needed for mitochondria to produce energy, led to an early loss of axonal function in dopaminergic neurons. This axonal deficit impaired the ability to communicate with distant parts of the basal ganglia, particularly the striatum. Only later was the ability of cell body to communicate with neighboring neurons lost.
It had previously been thought that impaired communication with the striatum was responsible for the movement difficulty experienced by patients with Parkinson’s. However, Surmeier’s group found that the axonal failure resulted in only modest deficits in learning and motor skills in mice. The key impairment in movement only appeared later, when dopaminergic neurons stopped communicating with their closest neighbors in the substantia nigra, a region that links the basal ganglia with the rest of the brain.
“We used intersectional genetics to specifically disrupt a key subunit in mitochondrial complex one, just in dopaminergic neurons,” Surmeier said. “This prevented mitochondria from generating ATP – the energy currency of cells. With this single genetic disruption, mice exhibited a progressive, levodopa-responsive Parkinsonism that closely mimicked the human disease. This observation demonstrated that loss of mitochondrial function alone was sufficient to produce a Parkinsonian phenotype.”
The staging of pathology in this model also allowed Surmeier’s group to test a long-held theory about the brain circuits responsible for the motor symptoms of Parkinson’s disease.
“The staging of behavioral deficits in the model revealed to us that although loss of dopaminergic signaling in the striatum was important, it wasn’t sufficient to cause the cardinal deficits of the disease,” Surmeier said.
Surmeier’s research and the award would not be possible without the efforts of colleagues, postdoctoral scholars, students and staff in his laboratory, he said.
In particular, the efforts of Patricia González-Rodríguez, PhD, a former postdoctoral scholar in Surmeier’s laboratory, were crucial to the findings of the paper in Nature, Surmeier said.
“This award is an honor, but it is important to remember that this was a team effort,” Surmeier said. “The award is a recognition of the effort made by an outstanding group of Northwestern scientists and staff.”
Additionally, Surmeier’s work was made possible by generous support from the Flanagan Foundation, the JPB Foundation and the Michael J. Fox Foundation, Surmeier said.