Direct Imaging of Modulatory Neurotransmitters Using Synthetic Nanosensors to Understand and Treat Parkinson s Disease
Abstract
Parkinson’s disease (PD) is a chronic, neurodegenerative disorder without a known cure. A hallmark of PD is the malfunction and eventual death of dopaminergic neurons in the brain, which have critical roles for both cognition and motor function. As these cells die, the levels of neurotransmitter dopamine change, leading to abnormal brain function, including uncontrolled movements and eventually dementia. Despite a century of research on PD, we have neither a complete understanding of its cause nor an effective cure. To alleviate symptoms, patients are prescribed levodopa (L-DOPA), a drug that temporarily increases and stabilizes dopamine levels in areas of the brain impacted by PD. However, as time progresses, continued treatment with L-DOPA disrupts natural brain function, leading to the development of dyskinesia, or uncontrolled involuntary muscle movements. Our shortcomings in both understanding and treating PD with drugs like L-DOPA are due to a lack of tools available to truly observe and understand brain function at the level of neurotransmission of molecules such as dopamine in the brain. In this project, we aim to implement near-infrared fluorescent nanosensors that would enable us to visualize dopamine neurotransmission at microscopic levels in brain tissue in real-time. Specifically, we will validate these techniques in living brain tissues extracted from Parkinson’s disease mice models. Owing to the transparency of brain tissue to near-infrared light, these nanosensors could one day enable imaging of neurotransmission in awake, behaving animals to study long-term changes in neuroplasticity as PD develops and is treated with L-DOPA. These insights would improve our understanding of PD progression and inform future diagnostic and therapeutic approaches. The proposed research plan combines the efforts of scientists with expertise in nanotechnology, optics, and neuroscience to achieve success through a collaborative effort and training experience for the Principal Investigator (PI). This novel, interdisciplinary research plan will provide a unique experience for the PI to start a research program at an institution where this approach can be used to continue investigation into PD research while expanding into the study of other neurological diseases and answering fundamental questions in the field of neurotransmission.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810282
Entities
People
- Jackson Del Bonis-o Donnell
Organizations
- United States Army
- University of California, Berkeley