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

Purpose The nicotinic acetylcholine alpha-7 receptors (alpha 7R) 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-[F-18]fluorodibenzo[b,d]thiophene-5,5-dioxide) in a rat model mimicking early stages of PD. Procedures PET imaging of alpha 7R 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 alpha 7R 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 alpha 7R in animal models of PD and highlight the requirement to use a potential neuroprotective approach through alpha 7R ligands at the early stages of PD.