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Longitudinal PET Imaging of α7 Nicotinic Acetylcholine Receptors with [18F]ASEM in a Rat Model of Parkinson’s Disease

  • Steven Vetel
  • Johnny Vercouillie
  • Frédéric Buron
  • Jackie Vergote
  • Clovis Tauber
  • Julie Busson
  • Gabrielle Chicheri
  • Sylvain Routier
  • Sophie Sérrière
  • Sylvie ChalonEmail author
Research Article

Abstract

Purpose

The nicotinic acetylcholine alpha-7 receptors (α7R) are involved in a number of neuropsychiatric and neurodegenerative brain disorders such as Parkinson’s disease (PD). However, their specific pathophysiologic roles are still unclear. In this context, we studied the evolution of these receptors in vivo by positron emission tomography (PET) imaging using the recently developed tracer 3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-[18F]fluorodibenzo[b,d]thiophene-5,5-dioxide) in a rat model mimicking early stages of PD.

Procedures

PET imaging of α7R was performed at 3, 7, and 14 days following a partial striatal unilateral lesion with 6-hydroxydopamine in adult rats. After the last imaging experiments, the status of nigro-striatal dopamine neurons as well as different markers of neuroinflammation was evaluated on brain sections by autoradiographic and immunofluorescent experiments.

Results

We showed an early and transitory rise in α7R expression in the lesioned striatum and substantia nigra, followed by over-expression of several gliosis activation markers in these regions of interest.

Conclusions

These findings support a longitudinally follow-up of α7R in animal models of PD and highlight the requirement to use a potential neuroprotective approach through α7R ligands at the early stages of PD.

Key words

Dopamine neurotransmission Neurodegeneration Neuroinflammation Microglia M1/M2 phenotype 

Notes

Acknowledgments

We thank the Laboratories Cyclopharma for providing fluor-18 and Sylvie Bodard for technical assistance.

Funding Information

This work was supported by the European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement No. 278850 (INMiND), by Labex IRON (ANR-11-LABX-18-01), and by the Région Centre-Val de Loire project BIAlz (No. 2014 00091547).

Compliance with Ethical Standards

All procedures were conducted in accordance with the requirements of the European Community Council Directive 2010/63/EU for the care of laboratory animals and with the authorization of the Regional Ethical Committee (Authorization No. 2016.022218004689 and No. 00434.02).

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

11307_2019_1400_MOESM1_ESM.pdf (176 kb)
ESM 1 (PDF 175 kb)

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Copyright information

© World Molecular Imaging Society 2019

Authors and Affiliations

  • Steven Vetel
    • 1
  • Johnny Vercouillie
    • 1
    • 2
  • Frédéric Buron
    • 3
  • Jackie Vergote
    • 1
  • Clovis Tauber
    • 1
  • Julie Busson
    • 1
  • Gabrielle Chicheri
    • 1
  • Sylvain Routier
    • 3
  • Sophie Sérrière
    • 1
  • Sylvie Chalon
    • 1
    Email author
  1. 1.UMR Inserm U1253, iBrainUniversité de Tours, UFR de MédecineTours Cedex 01France
  2. 2.INSERM CIC 1415University HospitalToursFrance
  3. 3.Institut de Chimie Organique et Analytique, ICOA, UMR CNRS 7311Université d’OrléansOrleansFrance

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