Objective: To investigate possible alterations in the 5-HT₄ serotonergic receptor in the brain of patients with PD at a relatively early stage, compared with healthy volunteers of the same age, and to examine the links between the availability of this receptor and motor, cognitive and neuropsychiatric symptoms.

Background: In addition to dopaminergic degeneration, the pathophysiology of Parkinson’s disease (PD) involves alterations in the serotonergic system. Beyond the presynaptic side, there is growing interest in postsynaptic receptors, particularly the 5-HT₄ receptor, whose expression is altered in cases of abnormal eating behaviour, mood disorders and cognitive deficits. Surprisingly, no clinical study has yet investigated the 5-HT₄ receptor in PD, even though the myriad of non-motor symptoms of PD encompasses such manifestations.

Method: Twenty subjects with relatively early-stage PD and fifteen age-matched healthy volunteers (HV) underwent a multimodal assessment comprising neurological, neuropsychological and neuropsychiatric evaluations, T1-weighted structural MRI, and PET imaging using the 5-HT₄ receptor-specific radioligand [¹¹C]SB207145. Analyses by region of interest and voxel-wise (using statistical parametric mapping) were performed to compare the non-displaceable binding potential (BP_ND) between the groups. Correlations were sought between changes in BP_ND and the various assessment scores.

Results: Preliminary data show a significant reduction in binding in the bilateral substantia nigra and brainstem, and a significant increase in binding in the bilateral putamen in PD subjects compared with HV. Further analyses will be conducted to determine whether gender has an impact on binding and whether changes in BP_ND correlate with certain assessment scores.

Conclusion: Overall, these results highlight a potential role for the 5-HT₄ receptor in the pathophysiology of PD in the early stages of the illness. Further research will be needed to determine whether 5-HT₄ receptor availability changes reflect a compensatory mechanism or contribute to the pathophysiology of particular symptoms.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/exploratory-study-of-brain-5-ht4-receptor-availability-in-early-stage-parkinsons-disease/