Abstract

BackgroundSerotonergic neurons in the rodent hypothalamus are implicated in key neuroendocrine and metabolic functions, including circadian rhythmicity. However, the assessment of the serotonergic system in the human hypothalamus in vivo is difficult as delineation of the hypothalamus is cumbersome with conventional region-of-interest analysis. In the present study, we aimed to develop a method to visualize serotonin transporters (SERT) in the hypothalamus. Additionally, we tested the hypothesis that hypothalamic SERT binding ratios are different between patients with hypothalamic impairment (HI), pituitary insufficiency (PI), and control subjects (C).MethodsSERT availability was determined in 17 subjects (6 HI, 5 PI, and 6 healthy controls), 2 h after injection of 123I-N-ω-fluoropropyl-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane ([123I]FP-CIT), using single-photon emission computed tomography (performed on a brain-dedicated system) fused with individual magnetic resonance imaging (MRI) scans of the brain. The hypothalamus (representing specific SERT binding) and cerebellum (representing nonspecific binding) were manually delineated on each MRI to assess [123I]FP-CIT binding and specific-to-nonspecific binding ratios.ResultsIn each healthy subject, [123I]FP-CIT binding was higher in the hypothalamus than in the cerebellum, and the mean hypothalamic binding ratio of SERT was 0.29 ± 0.23. We found no difference in hypothalamic binding ratios between HI, PI, and control subjects (HI 0.16 ± 0.24, PI 0.45 ± 0.39, C 0.29 ± 0.23, p value 0.281).ConclusionsWe were able to demonstrate SERT binding in the human hypothalamus in vivo. However, we did not find altered hypothalamic SERT binding in patients with hypothalamic impairment.Trial registrationNetherlands Trial Register: NTR2520

Highlights

  • Serotonergic neurons in the rodent hypothalamus are implicated in key neuroendocrine and metabolic functions, including circadian rhythmicity

  • singlephoton emission computed tomography (SPECT) measures of serotonin transporters (SERT) in the hypothalamus in healthy control subjects In each healthy control subject, [123I]FP-CIT binding was higher in the hypothalamus than in the cerebellum, and the mean hypothalamic binding ratio of SERT was 0.29 ± 0.23

  • We found no difference in the hypothalamic binding ratios of SERT between hypothalamic impairment (HI), pituitary insufficiency (PI), and control subjects (HI 0.16 ± 0.24, PI 0.45 ± 0.39, C 0.29 ± 0.23, p value 0.281)

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Summary

Introduction

Serotonergic neurons in the rodent hypothalamus are implicated in key neuroendocrine and metabolic functions, including circadian rhythmicity. The human hypothalamus is a small brain structure of only 4 ml in the diencephalon that directs a multitude of important functions in the body, including pituitary hormone release, diurnal rhythmicity, energy homeostasis, and autonomic regulation [1]. Imaging of serotonin transporters (SERT) with singlephoton emission computed tomography (SPECT) or positron emission tomography (PET) provides an important opportunity to study the serotonergic system in vivo. The expression of SERT in the hypothalamus was poorly defined as spatial resolution of nuclear imaging techniques is limited, and delineation of a structure as small and heterogeneous as the hypothalamus is cumbersome with conventional region-of-interest (ROI) analysis [20]. Only one study demonstrated hypothalamic SERT binding using PET and [11C]DASB, the delineation of the hypothalamus was not strictly defined [21]

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