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The iron-dopamine D1 coupling modulates neural signatures of working memory across adult lifespan
Aging Research Center, Karolinska Institutet and Stockholm University, Sweden.
Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).ORCID iD: 0000-0002-4501-4735
Aging Research Center, Karolinska Institutet and Stockholm University, Sweden.
Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).ORCID iD: 0000-0003-4743-6365
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2023 (English)In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 279, article id 120323Article in journal (Refereed) Published
Abstract [en]

Brain iron overload and decreased integrity of the dopaminergic system have been independently reported as brain substrates of cognitive decline in aging. Dopamine (DA), and iron are co-localized in high concentrations in the striatum and prefrontal cortex (PFC), but follow opposing age-related trajectories across the lifespan. DA contributes to cellular iron homeostasis and the activation of D1-like DA receptors (D1DR) alleviates oxidative stress-induced inflammatory responses, suggesting a mutual interaction between these two fundamental components. Still, a direct in-vivo study testing the iron-D1DR relationship and their interactions on brain function and cognition across the lifespan is rare. Using PET and MRI data from the DyNAMiC study (n=180, age=20-79, %50 female), we showed that elevated iron content was related to lower D1DRs in DLPFC, but not in striatum, suggesting that dopamine-rich regions are less susceptible to elevated iron. Critically, older individuals with elevated iron and lower D1DR exhibited less frontoparietal activations during the most demanding task, which in turn was related to poorer working-memory performance. Together, our findings suggest that the combination of elevated iron load and reduced D1DR contribute to disturbed PFC-related circuits in older age, and thus may be targeted as two modifiable factors for future intervention.

Place, publisher, year, edition, pages
Elsevier, 2023. Vol. 279, article id 120323
Keywords [en]
Age, BOLD, Dopamine, Iron, Working memory
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:umu:diva-214277DOI: 10.1016/j.neuroimage.2023.120323PubMedID: 37582419Scopus ID: 2-s2.0-85168445561OAI: oai:DiVA.org:umu-214277DiVA, id: diva2:1795927
Funder
Swedish Research Council, 2016-01936Swedish Research Council, 2014-00940Swedish Research Council, 2018-01327Knut and Alice Wallenberg FoundationRiksbankens Jubileumsfond, P20- 0515The Karolinska Institutet's Research Foundation, 2019-00916Swedish National Infrastructure for Computing (SNIC)Available from: 2023-09-11 Created: 2023-09-11 Last updated: 2023-09-11Bibliographically approved

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Johansson, JarkkoAndersson, MicaelSalami, Alireza

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Department of Radiation SciencesUmeå Centre for Functional Brain Imaging (UFBI)Department of Integrative Medical Biology (IMB)Wallenberg Centre for Molecular Medicine at Umeå University (WCMM)
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