Neuromolecular imaging in Parkinson's disease

Abstract Neuromolecular imaging (NMI) visually links electrical and chemical brain activity with neurotransmitter release in vivo, in real time and online to identify biomarkers to diagnose and treat neurodegenerative disorders such as Parkinson's disease (PD). NMI combined with BRODERICK PROBE laurate nanobiosensors image neuromolecules as the molecular transmitter crosses synaptically in the same motor neurons in basal ganglia as striatal motor neurons in basal ganglia direct movement. With NMI, striatal motor neurons function as electrical devices to synchronize instantaneously with the BRODERICK PROBE nanobiosensor to signal functional physiology (non-PD) or dysfunctional pathology (PD). In non-PD, neurons signal monoamines, precursors, and metabolites selectively with and without L-3,4-dihydroxyphenylalanine ( l -DOPA), while in PD, neurons signal peptides revealing the likely etiology of PD as the BRODERICK PROBE sees inside the PD brain and allows a direct cause and effect in PD per se and then further provides a direct online image inside the non-PD brain. NMI studies were further contrasted with PD versus non-PD responses after administration of the pharmaceutical, indirect agonist, bromocriptine (Parlodel). PD and non-PD animals were videotracked, and images were readily seen on a laptop via a potentiostat using a semiderivative electrical circuit. PD lesions with 6-hydroxydopamine (6-OHDA) were performed in substantia nigra pars compacta by Charles River surgeons. Administered l -DOPA doses were 50 and 100 mg/kg intraperitoneally; the same experimental paradigm was used to image PD versus non-PD animal models. Results showed that the baseline release of biogenic amine molecules was significantly above detection limits in non-PD animals and further increased dramatically in a linear dose response pattern after l -DOPA administration, whereas the PD model showed distinct pathology for baseline signally in basal ganglia. There were little or no biogenic amines. In fact, peptides and amino acid, l -tryptophan, were signaled instead of biogenic amines; and after l -DOPA, dramatic off-scale peptide and amino acid release was imaged, and the response was nonlinear. Indeed, there was no statistical difference between responses after the low dose in contrast to the higher dose l -DOPA in the PD animal model. Thus, NMI demonstrates for the first time that the actual online absence of the biogenic amine, catecholamine, dopamine, and the periodic absence of the indoleamine, serotonin, are empirical biomarkers for PD. Significant biomarkers present in PD and absent in non-PD animals include peptide neurotransmitters, dynorphin and somatostatin; l -DOPA significantly increased dynorphin, a glutamate toxin, and somatostatin, a protector in PD, but could not enable release of catecholamines or indolamines. It is intriguing that PD animals released the precursor to serotonin, that is, l -tryptophan, to a strikingly similar degree as was seen in signals imaged for the peptide biomarkers in PD, showing that the neurotransmitter biogenic amine, serotonin, as well at l -tryptophan, and the absence of dopamine are live biomarkers for PD, in fact, as critical as are the peptide biomarkers. The data enable cutting-edge and never-before-shown advances in the field of PD and nanobiotechnology specifically for unique diagnostic, surgical, and pharmacotherapeutic relief from debilitating PD.