Manganese-Enhanced Magnetic Resonance Imaging for Detection of Vasoactive Intestinal Peptide Receptor 2 Agonist Therapy in a Model of Parkinson's Disease.

Abstract

Neuroprotective immunity is defined by transformation of T-cell polarity for therapeutic gain. For neurodegenerative disorders and specifically for Parkinson's disease (PD), granulocyte-macrophage colony stimulating factor or vasoactive intestinal peptide receptor 2 (VIPR2) agonists elicit robust anti-inflammatory microglial responses leading to neuronal sparing in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice. While neurotherapeutic potential was demonstrated for PD, there remain inherent limitations in translating these inventions from the laboratory to patients. One obstacle in translating such novel neurotherapeutics centers on the availability of suitable noninvasive methods to track disease progression and therapeutic efficacy. To this end, we developed manganese-enhanced magnetic resonance imaging (MEMRI) assays as a way to track a linkage between glial activation and VIPR2 agonist (LBT-3627)-induced neuroprotective immunity for MPTP-induced nigrostriatal degeneration. Notably, LBT-3627-treated, MPTP-intoxicated mice show reduced MEMRI brain signal intensities. These changes paralleled reduced astrogliosis and resulted in sparing of nigral tyrosine hydroxylase neurons. Most importantly, the data suggest that MEMRI can be developed as a biomarker tool to monitor neurotherapeutic responses that are relevant to common neurodegenerative disorders used to improve disease outcomes.

• Authors: Katherine E Olson, Aditya N Bade, Charles R Schutt, Jingdong Dong, Scott J Shandler, Michael D Boska, R Lee Mosley, Howard E Gendelman, Yutong Liu
• Journal: Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics (Neurotherapeutics) Vol. 13 Issue 3 Pg. 635-46 (07 2016) ISSN: 1878-7479 [Electronic] United States
• PMID: 27329163 (Publication Type: Journal Article, Review, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• LBT-3627
• Neuroprotective Agents
• Oligopeptides
• Receptors, Vasoactive Intestinal Peptide, Type II
• Manganese
• Protein-Tyrosine Kinases

Topics

• Animals
• Brain (diagnostic imaging, drug effects)
• Dopaminergic Neurons (drug effects, metabolism)
• Image Enhancement (methods)
• Magnetic Resonance Imaging (methods)
• Male
• Manganese (administration & dosage)
• Mice
• Mice, Inbred C57BL
• Microglia (drug effects, metabolism)
• Neuroprotective Agents (administration & dosage)
• Oligopeptides (administration & dosage)
• Parkinson Disease (diagnostic imaging, drug therapy, immunology)
• Parkinsonian Disorders (diagnostic imaging, drug therapy, immunology)
• Protein-Tyrosine Kinases (metabolism)
• Receptors, Vasoactive Intestinal Peptide, Type II (agonists)