title: 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.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Olson
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Aditya N
authors.initials: AN
authors.lastname: Bade
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Schutt
authors.affiliation: Department of Radiology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Jingdong
authors.initials: J
authors.lastname: Dong
authors.affiliation: Longevity Biotech, Philadelphia, PA, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Shandler
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.|Department of Radiology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Boska
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: R Lee
authors.initials: RL
authors.lastname: Mosley
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA. hegendel@unmc.edu.
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.|Department of Radiology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D007089:Image Enhancement / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008345:Manganese / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage; D009842:Oligopeptides / Q000008:administration & dosage*; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000276:immunology; D020734:Parkinsonian Disorders / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000819:agonists*
chemical_list: C000606754:LBT-3627; D018696:Neuroprotective Agents; D009842:Oligopeptides; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D008345:Manganese; D011505:Protein-Tyrosine Kinases
keywords: MPTP; Magnetic resonance imaging (MRI); glial activation; inflammation; manganese enhanced MRI (MEMRI); neuroprotection