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

Katherine E. Olson, Aditya N. Bade, Charles R. Schutt, Jingdong Dong, Scott J. Shandler, Michael D. Boska, R Lee Mosley, Howard Eliot Gendelman, Yutong Liu

Research output: Contribution to journalReview article

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)635-646
Number of pages12
JournalNeurotherapeutics
Volume13
Issue number3
DOIs
StatePublished - Jul 1 2016

Fingerprint

Receptors, Vasoactive Intestinal Peptide, Type II
Manganese
Parkinson Disease
Magnetic Resonance Imaging
Neurodegenerative Diseases
Immunity
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Cell Polarity
Tyrosine 3-Monooxygenase
Substantia Nigra
Granulocyte-Macrophage Colony-Stimulating Factor
Neuroglia
Disease Progression
Anti-Inflammatory Agents
Therapeutics
Biomarkers
T-Lymphocytes
Neurons
Brain
4-phenyl-1,2,3,6-tetrahydropyridine

Keywords

  • MPTP
  • Magnetic resonance imaging (MRI)
  • glial activation
  • inflammation
  • manganese enhanced MRI (MEMRI)
  • neuroprotection

ASJC Scopus subject areas

  • Pharmacology
  • Clinical Neurology
  • Pharmacology (medical)

Cite this

Manganese-Enhanced Magnetic Resonance Imaging for Detection of Vasoactive Intestinal Peptide Receptor 2 Agonist Therapy in a Model of Parkinson’s Disease. / Olson, Katherine E.; Bade, Aditya N.; Schutt, Charles R.; Dong, Jingdong; Shandler, Scott J.; Boska, Michael D.; Mosley, R Lee; Gendelman, Howard Eliot; Liu, Yutong.

In: Neurotherapeutics, Vol. 13, No. 3, 01.07.2016, p. 635-646.

Research output: Contribution to journalReview article

Olson, Katherine E. ; Bade, Aditya N. ; Schutt, Charles R. ; Dong, Jingdong ; Shandler, Scott J. ; Boska, Michael D. ; Mosley, R Lee ; Gendelman, Howard Eliot ; Liu, Yutong. / Manganese-Enhanced Magnetic Resonance Imaging for Detection of Vasoactive Intestinal Peptide Receptor 2 Agonist Therapy in a Model of Parkinson’s Disease. In: Neurotherapeutics. 2016 ; Vol. 13, No. 3. pp. 635-646.
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