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

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.

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Acknowledgments

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

Funding

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).

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Correspondence to Sylvie Chalon.

Ethics declarations

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).

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The authors declare that they have no conflict of interest.

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Vetel, S., Vercouillie, J., Buron, F. et al. Longitudinal PET Imaging of α7 Nicotinic Acetylcholine Receptors with [18F]ASEM in a Rat Model of Parkinson’s Disease. Mol Imaging Biol 22, 348–357 (2020). https://doi.org/10.1007/s11307-019-01400-y

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Key words

  • Dopamine neurotransmission
  • Neurodegeneration
  • Neuroinflammation
  • Microglia
  • M1/M2 phenotype