Dopamine Signaling in Substantia Nigra and Its Impact on Locomotor Function-Not a New Concept, but Neglected Reality

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dc.creatorSalvatore, Michael F.
dc.creator.orcid0000-0003-0217-5093 (Salvatore, Michael F.)
dc.date.accessioned2024-02-14T15:35:54Z
dc.date.available2024-02-14T15:35:54Z
dc.date.issued2024-01-23
dc.description.abstractThe mechanistic influences of dopamine (DA) signaling and impact on motor function are nearly always interpreted from changes in nigrostriatal neuron terminals in striatum. This is a standard practice in studies of human Parkinson's disease (PD) and aging and related animal models of PD and aging-related parkinsonism. However, despite dozens of studies indicating an ambiguous relationship between changes in striatal DA signaling and motor phenotype, this perseverating focus on striatum continues. Although DA release in substantia nigra (SN) was first reported almost 50 years ago, assessment of nigral DA signaling changes in relation to motor function is rarely considered. Whereas DA signaling has been well-characterized in striatum at all five steps of neurotransmission (biosynthesis and turnover, storage, release, reuptake, and post-synaptic binding) in the nigrostriatal pathway, the depth of such interrogations in the SN, outside of cell counts, is sparse. However, there is sufficient evidence that these steps in DA neurotransmission in the SN are operational and regulated autonomously from striatum and are present in human PD and aging and related animal models. To complete our understanding of how nigrostriatal DA signaling affects motor function, it is past time to include interrogation of nigral DA signaling. This brief review highlights evidence that changes in nigral DA signaling at each step in DA neurotransmission are autonomous from those in striatum and changes in the SN alone can influence locomotor function. Accordingly, for full characterization of how nigrostriatal DA signaling affects locomotor activity, interrogation of DA signaling in SN is essential.
dc.description.sponsorshipThis research was funded by US Department of Defense U.S. Army Medical Research and Material Command Congressionally Directed Medical Research Program (grant number W81XWH19-1-0757), the National Institute on Aging (grant number AG040261), and the American Federation for Aging Research (grant number 110301090A). The APC was funded by W81XWH-19-1-0757.
dc.identifier.citationSalvatore M. F. (2024). Dopamine Signaling in Substantia Nigra and Its Impact on Locomotor Function-Not a New Concept, but Neglected Reality. International journal of molecular sciences, 25(2), 1131. https://doi.org/10.3390/ijms25021131
dc.identifier.issn1422-0067
dc.identifier.issue2
dc.identifier.urihttps://hdl.handle.net/20.500.12503/32504
dc.identifier.volume25
dc.publisherMDPI
dc.relation.urihttps://doi.org/10.3390/ijms25021131
dc.rights.holder© 2024 by the author.
dc.rights.licenseAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceInternational Journal of Molecular Sciences
dc.subjectParkinson's disease
dc.subjectaging
dc.subjectdopamine
dc.subjectdopamine receptor
dc.subjectnigrostriatal
dc.subjectphosphorylation
dc.subjectreuptake
dc.subjectstriatum
dc.subjecttyrosine hydroxylase
dc.subject.meshDopamine
dc.subject.meshParkinson Disease
dc.titleDopamine Signaling in Substantia Nigra and Its Impact on Locomotor Function-Not a New Concept, but Neglected Reality
dc.typeArticle
dc.type.materialtext

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