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| Hauptseite > Publikationsdatenbank > Functional MRI Derived Resting-State Alterations in Huntington’s Disease are Associated With the Distribution of Serotonergic and Dopaminergic Neurotransmitter Systems |
| Hauptseite > Publikationsdatenbank > Functional MRI Derived Resting-State Alterations in Huntington’s Disease are Associated With the Distribution of Serotonergic and Dopaminergic Neurotransmitter Systems |
| Abstract | FZJ-2021-05267 |
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2021
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Please use a persistent id in citations: doi:10.1016/j.biopsych.2021.02.440
Abstract: Huntington’s disease (HD) is characterized by progressive striatal atrophy and widespreaddegeneration during the course of disease. Functionally, altered resting-state activity andconnectivity in networks involving cortical, subcortical and cerebellar regions can beobserved. The relationship of brain alterations in HD with specific neurotransmitter systemsremains largely unknown. We evaluated whether resting-state alterations in HD are associated with the known in vivodistribution of various neurotransmitter systems including serotonin, GABA, dopamine andnorepinephrine. Maps of resting-state activity derived from functional magnetic resonanceimaging were computed for 32 HD patients and 30 healthy controls. We tested whetheralterations in HD were associated with the distribution of specific neurotransmitter systemsand their coding mRNA gene expressions. Finally, we examined the association of theserelationships with HD clinical phenotypes and if these associations can be replicated in anindependent cohort (HD: N=29; controls: N=39).HD functional alterations were significantly related to the distribution of dopamine andserotonin receptors (D1, D2, 5-HT1b) and transporters, as well as with mRNA expressions ofgenes encoding the corresponding dopamine proteins. The co-localization with D1 wascorrelated in HD with motor (r=-0.5,p=0.004) and functional (r=0.5,p=0.003) impairment.These findings were largely replicated in a second cohort.We show that resting-state functional alterations in HD follow the spatial distribution ofdopaminergic and serotonergic systems. The strength of these associations was linked to theobserved symptom severity. These findings provide novel insight intoneuropathophysiological mechanisms underlying functional alterations in HD and thisapproach may aid characterizing less researched neurodegenerative diseases.
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