Dopaminergic, serotonergic, and noradrenergic deficits in Parkinson disease
- PMID: 26478895
- PMCID: PMC4603378
- DOI: 10.1002/acn3.246
Dopaminergic, serotonergic, and noradrenergic deficits in Parkinson disease
Abstract
Objective: People with Parkinson disease (PD) frequently develop dementia, which is associated with neocortical deposition of alpha-synuclein (α-syn) in Lewy bodies and Lewy neurites. In addition, neuronal loss and deposition of aggregated α-syn also occur in multiple subcortical nuclei that project to neocortical, limbic, and basal ganglia regions. Therefore, we quantified regional deficits in innervation from these PD-affected subcortical nuclei, by measuring the neurotransmitters and neurotransmitter transporter proteins originating from projections of dopaminergic neurons in substantia nigra pars compacta, serotonergic neurons in dorsal raphé nuclei, noradrenergic neurons in locus coeruleus, and cholinergic neurons in nucleus basalis of Meynert.
Methods: High-performance liquid chromatography and novel enzyme-linked immunosorbent assays were performed to quantify dopaminergic, serotonergic, noradrenergic, and cholinergic innervation in postmortem brain tissue. Eight brain regions from 15 PD participants (with dementia and Braak stage 6 α-syn deposition) and six age-matched controls were tested.
Results: PD participants compared to controls had widespread reductions of dopamine transporter in caudate, amygdala, hippocampus, inferior parietal lobule (IPL), precuneus, and visual association cortex (VAC) that exceeded loss of dopamine, which was only significantly reduced in caudate and amygdala. In contrast, PD participants had comparable deficits of both serotonin and serotonin transporter in caudate, middle frontal gyrus, IPL, and VAC. PD participants also had significantly reduced norepinephrine levels for all eight brain regions tested. Vesicular acetylcholine transporter levels were only quantifiable in caudate and hippocampus and did not differ between PD and control groups.
Interpretation: These results demonstrate widespread deficits in dopaminergic, serotonergic, and noradrenergic innervation of neocortical, limbic, and basal ganglia regions in advanced PD with dementia.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4603378/bin/acn30002-0949-f1.gif)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4603378/bin/acn30002-0949-f2.gif)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4603378/bin/acn30002-0949-f3.gif)
Similar articles
-
Serotonergic markers in Parkinson's disease and levodopa-induced dyskinesias.Mov Disord. 2015 May;30(6):796-804. doi: 10.1002/mds.26144. Epub 2015 Feb 4. Mov Disord. 2015. PMID: 25649148
-
Hippocampal Lewy pathology and cholinergic dysfunction are associated with dementia in Parkinson's disease.Brain. 2014 Sep;137(Pt 9):2493-508. doi: 10.1093/brain/awu193. Epub 2014 Jul 24. Brain. 2014. PMID: 25062696
-
Cognitive dysfunction and dementia in Parkinson's disease.J Neural Transm (Vienna). 2004 Oct;111(10-11):1303-15. doi: 10.1007/s00702-004-0168-1. Epub 2004 Jun 30. J Neural Transm (Vienna). 2004. PMID: 15480840 Review.
-
Alpha-synuclein pathology in Parkinson's and Alzheimer's disease brain: incidence and topographic distribution--a pilot study.Acta Neuropathol. 2003 Sep;106(3):191-201. doi: 10.1007/s00401-003-0725-y. Epub 2003 Jul 5. Acta Neuropathol. 2003. PMID: 12845452
-
Post mortem studies in Parkinson's disease--is it possible to detect brain areas for specific symptoms?J Neural Transm Suppl. 1999;56:1-29. doi: 10.1007/978-3-7091-6360-3_1. J Neural Transm Suppl. 1999. PMID: 10370901 Review.
Cited by
-
Non-motor symptoms associated with progressive loss of dopaminergic neurons in a mouse model of Parkinson's disease.Front Neurosci. 2024 Apr 30;18:1375265. doi: 10.3389/fnins.2024.1375265. eCollection 2024. Front Neurosci. 2024. PMID: 38745938 Free PMC article.
-
A Mutual Nexus Between Epilepsy and α-Synuclein: A Puzzle Pathway.Mol Neurobiol. 2024 May 4. doi: 10.1007/s12035-024-04204-6. Online ahead of print. Mol Neurobiol. 2024. PMID: 38703341 Review.
-
Impact of Acute Dopamine Replacement on Cognitive Function in Parkinson's Disease.Mov Disord Clin Pract. 2024 May;11(5):534-542. doi: 10.1002/mdc3.14017. Epub 2024 Mar 12. Mov Disord Clin Pract. 2024. PMID: 38470011
-
Alterations of Cortical Structure and Neurophysiology in Parkinson's Disease Are Aligned with Neurochemical Systems.Ann Neurol. 2024 Apr;95(4):802-816. doi: 10.1002/ana.26871. Epub 2024 Jan 12. Ann Neurol. 2024. PMID: 38146745
-
Tongue and laryngeal exercises improve tongue strength and vocal function outcomes in a Pink1-/- rat model of early Parkinson disease.Behav Brain Res. 2024 Mar 5;460:114754. doi: 10.1016/j.bbr.2023.114754. Epub 2023 Nov 20. Behav Brain Res. 2024. PMID: 37981125
References
-
- Braak H, Ghebremedhin E, Rub U, et al. Stages in the development of Parkinson's disease-related pathology. Cell Tissue Res. 2004;318:121–134. - PubMed
-
- Gesi M, Soldani P, Giorgi FS, et al. The role of the locus coeruleus in the development of Parkinson's disease. Neurosci Biobehav Rev. 2000;24:655–668. - PubMed
-
- Guttman M, Boileau I, Warsh J, et al. Brain serotonin transporter binding in non-depressed patients with Parkinson's disease. Eur J Neurol. 2007;14:523–528. - PubMed
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous