TY - JOUR
T1 - The role of phosphodiesterase 4 in excessive daytime sleepiness in Parkinson's disease
AU - Wilson, Heather
AU - Pagano, Gennaro
AU - Niccolini, Flavia
AU - Muhlert, Nils
AU - Mehta, Mitul A.
AU - Searle, Graham
AU - Gunn, Roger N.
AU - Rabiner, Eugenii A.
AU - Foltynie, Thomas
AU - Politis, Marios
PY - 2019/2/22
Y1 - 2019/2/22
N2 -
Introduction: Preclinical studies suggest a link between cAMP/PKA signalling, phosphodiesterase 4 (PDE4) expression and excessive daytime sleepiness (EDS). Here, we investigated in vivo the association between PDE4 expression and EDS in Parkinson's disease (PD) patients using [
11
C]rolipram PET and MR imaging. Methods: Eighteen participants, 12 PD and 6 healthy controls, underwent one [
11
C]rolipram PET and a multi-modal MRI scan. Probabilistic tractography was performed on subjects’ diffusion data to functionally parcellate the striatum according with projections to limbic cortical areas. The severity of EDS was assessed using the Epworth Sleepiness Scale (ESS). To assess PDE4 expression in PD patients with EDS, the PD cohort was divided according to the presence (n = 5) or absence (n = 7) of EDS, defined using validated cut-off of score ≥10 on the ESS as score ≥10 on the ESS. Results: PD patients with EDS showed significantly increased [
11
C]rolipram volume of distribution (V
T
) in the caudate (P = 0.029), hypothalamus (P = 0.013), hippocampus (P = 0.036) and limbic striatum (P = 0.030) compared to patients without EDS. Furthermore, higher ESS scores correlated with increased [
11
C]rolipram V
T
in the caudate (r = 0.77; P = 0.003), hypothalamus (r = 0.84; P = 0.001), hippocampus (r = 0.81; P = 0.001) and limbic subdivisions of the striatum (r = 0.80; P = 0.003). Conclusion: Our findings translate into humans preclinical data indicating that EDS is associated with elevated PDE4 in regions regulating sleep. The severity of EDS in PD was associated with elevated PDE4 expression; thus, suggesting a role of PDE4 in the pathophysiology of EDS in PD.
AB -
Introduction: Preclinical studies suggest a link between cAMP/PKA signalling, phosphodiesterase 4 (PDE4) expression and excessive daytime sleepiness (EDS). Here, we investigated in vivo the association between PDE4 expression and EDS in Parkinson's disease (PD) patients using [
11
C]rolipram PET and MR imaging. Methods: Eighteen participants, 12 PD and 6 healthy controls, underwent one [
11
C]rolipram PET and a multi-modal MRI scan. Probabilistic tractography was performed on subjects’ diffusion data to functionally parcellate the striatum according with projections to limbic cortical areas. The severity of EDS was assessed using the Epworth Sleepiness Scale (ESS). To assess PDE4 expression in PD patients with EDS, the PD cohort was divided according to the presence (n = 5) or absence (n = 7) of EDS, defined using validated cut-off of score ≥10 on the ESS as score ≥10 on the ESS. Results: PD patients with EDS showed significantly increased [
11
C]rolipram volume of distribution (V
T
) in the caudate (P = 0.029), hypothalamus (P = 0.013), hippocampus (P = 0.036) and limbic striatum (P = 0.030) compared to patients without EDS. Furthermore, higher ESS scores correlated with increased [
11
C]rolipram V
T
in the caudate (r = 0.77; P = 0.003), hypothalamus (r = 0.84; P = 0.001), hippocampus (r = 0.81; P = 0.001) and limbic subdivisions of the striatum (r = 0.80; P = 0.003). Conclusion: Our findings translate into humans preclinical data indicating that EDS is associated with elevated PDE4 in regions regulating sleep. The severity of EDS in PD was associated with elevated PDE4 expression; thus, suggesting a role of PDE4 in the pathophysiology of EDS in PD.
KW - Diffusion tensor imaging
KW - Excessive daytime sleepiness
KW - Parkinson's disease
KW - Phosphodiesterase 4
KW - Positron emission tomography
KW - Rolipram
UR - http://www.scopus.com/inward/record.url?scp=85062017909&partnerID=8YFLogxK
U2 - 10.1016/j.parkreldis.2019.02.027
DO - 10.1016/j.parkreldis.2019.02.027
M3 - Article
AN - SCOPUS:85062017909
SN - 1353-8020
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
ER -