National Institute of Neurological Disorders and Stroke 5R01NS124777-05

Simultaneous PET/phMR studies on interplay of mGlu/dopamine receptors in PD-like neurodegeneration

This award funds research combining advanced imaging techniques (PET and phMRI) to study dopamine and glutamate receptor interactions in Parkinson's disease models, aiming to improve understanding and drug development for related neurodegenerative disorders.

Description

Research of the brain receptor functions holds a promise for better diagnostic tools and drugs that could be tailored to the individual needs, thereby eliminating or reducing side effects and even providing a way for prevention of disease. Real-time imaging of receptor modulation using simultaneous phMRI and PET will challenge the present theories of signaling and synaptic plasticity during degenerative processes. The results of receptor modulation can be utilized in drug development for dopamine-glutamate regulation related disorders such as Parkinson’s disease, schizophrenia, or drug abuse. The project involves developing high-level imaging instrumentation and techniques, as well as unique ligands, to conduct quantitative in vivo imaging studies of dopaminergic and glutamatergic neurofunction. It proposes to combine phMRI imaging of amphetamine-induced dopamine release or excessive synaptic glutamate concentration with PET imaging of mGluR4, mGluR5, and dopamine D2 receptor function to investigate neurodegeneration-induced modulation of neurotransmission using α-synuclein rat models of Parkinson’s disease and its additional 6-OHDA lesioned counterpart.

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