Real Time Imaging of Biomarkers in the Parkinson's Brain Using Mini-Implantable Biosensors. II. Pharmaceutical Therapy with Bromocriptine.

Patricia Broderick,Edwin Kolodny

doi:10.3390/ph2030236

Abstract

We used Neuromolecular Imaging (NMI) and trademarked BRODERICK PROBE® mini-implantable biosensors, to selectively and separately detect neuro-transmitters in vivo, on line, within seconds in the dorsal striatal brain of the Parkinson’s Disease (PD) animal model. We directly compared our results derived from PD to the normal striatal brain of the non-Parkinson’s Disease (non-PD) animal. This advanced biotechnology enabled the imaging of dopamine (DA), serotonin (5-HT), homovanillic acid (HVA) a metabolite of DA, L-tryptophan (L-TP) a precursor to 5-HT and peptides, dynorphin A 1-17 (Dyn A) and somatostatin (somatostatin releasing inhibitory factor) (SRIF). Each neurotransmitter and neurochemical was imaged at a signature electroactive oxidation/half-wave potential in dorsal striatum of the PD as compared with the non-PD animal. Both endogenous and bromocriptine-treated neurochemical profiles in PD and non-PD were imaged using the same experimental paradigm and detection sensitivities. Results showed that we have found significant neurotransmitter peptide biomarkers in the dorsal striatal brain of endogenous and bromocriptine-treated PD animals. The peptide biomarkers were not imaged in dorsal striatal brain of non-PD animals, either endogenously or bromocriptine-treated. These findings provide new pharmacotherapeutic strategies for PD patients. Thus, our findings are highly applicable to the clinical treatment of PD.

Highlights

The present data are derived from 10 Neuromolecular Imaging (NMI) studies in dorsal striatum of Parkinson’s Disease (PD) versus another 10 studies in non-Parkinson’s Disease (non-PD) animals
Results from PD and non-PD animals were compared by One-Way Analysis of Variance (ANOVA)
The effects of the pharmaceutical agent, routinely used to treat PD patients, bromocriptine (Parlodel®), was studied for its effects on neurochemical profiles for PD compared with non-PD

Summary

Introduction

PD exhibits multifaceted and debilitating symptoms; conventionally, though, we speak of PD as a neurodegenerative disease wherein there is a progressive impairment of movement. Some of these movement disorders are described as: (a) tremors (hands shaking while at rest), (b) rigidity (stiff, abrupt muscle movement) and (c) bradykinesia (being unable to start a particular movement, like walking). PD is caused by the loss of dopamine (DA) neurons in substantia nigra, the site for DA cell bodies in the basal ganglia, which are the motor neurons of the brain. One neuronal efferent terminal for the substantia nigra is the caudate putamen. The caudate putamen consists of two separate structures; in animals, the caudate and putamen are connected in one structure, dorsal striatum

Methods

Results

Conclusion